Vol. 6 (2), Oct.2012

May 2011

Objective: The iliac crest and L5 transverse process are potential barriers to proper needle placement in superior hypogastric plexus block (SHPB) for pelvic cancer pain. Several investigators report successful SHPB using a paramedian transdiscal approach. Another new single puncture approach, posteromedian transdiscal, has been described which can be performed with the patient in either lateralor prone position.Methods: Twenty-two patients were included in the study. Visual analog score, daily morphine consumption, duration of the procedure,side effects, and Quality of Life Questionnaire-C30 were recorded. Results: The duration of the procedure was 21.4±6.5 minutes.The mean visual analog score, daily morphine consumption, andQuality of Life Questionnaire-C30 score were significantly decreased. There was no neural injury, headache, discitis, or disc herniation. Conclusions: The posteromedian transdiscal approach to SHPB for cancer pain proved to be safe and reliable compared with the classic technique. No nerve or disc-related complications were notedKeywords: Superior hypogastric plexus block, posteromedian transdiscal approach, pelvic cancer pain

Background: Activation of herpes virus 6 (HHV6) has seen in Hodgkin’s and non-Hodgkin’s Lymphoma (HL&NHL) as a result of lymphoma associated immunosuppression. Multiple studies have suggested an association between both HHV6 and cytomegalovirus CMV for development of CMV disease affecting the pathogenesis of lymphoma. Therefore, this study investigated the frequency of HHV6, its impact on clinical manifestations of lymphoma and its possible association with risk for development of CMV infection in pediatric lymphoma patients. Methods: Presence of HHV6 DNA and CMV DNA was

investigated by PCR assay in both WBC’s and plasma samples from 50 patients diagnosed with HL or NHL. CMV antibody titer was also determined in sera obtained from each patient. Twenty apparently healthy siblings were used as a control group. Results: In a study group of 50 patients diagnosed with HL or NHL, 23/50 (46%) were found to be positive for herpes virus DNA (HHV6 or CMV) in WBC’s or plasma by PCR assay and this was significantly higher than its presence in the pediatric control group 2/20 (10%) (p = 0.005). Ten out of these 23 (43%) were found to have active CMV infection. Fifty six percent of patients with CMV infection were found among NHL cases with B- subtype. The presence of both herpes viruses DNA was significantly associated with more frequent episodes of febrile neutropenia (median 3 episodes), absolute neutrophil count (< 0.8), lymphocytes (< 0.5), and low hemoglobin level (< 9.1), (p < 0.05). Conclusion: The presence of HHV6 can be considered as a predicting indicator of cellular immunosuppression preceding the onset of CMV infection which may result in a severe outcome among pediatric lymphoma patientsKeywords: : HHV-6; CMV; Lymphoma; PCR

8228 Trimodality treatment for bladder cancer: does modern radiotherapy improve the end results?

Mohamed S. Zaghloul and Amr G Mousa

Expert Rev. Anticancer Ther. 10(12), 1933–1944 (2010

With the advancementin endoscopic surgery, radiation treatment planning and execution, as well as the use of new chemotherapeutic regimens, bladder conservation has evolved into a competing alternative to radical cystectomy. Trimodality treatment has the great advantage of preserving a normally functioning urinary bladder. Despite the absence of direct randomized trials comparing both modalities, trimodality treatment comprising maximal transuretheral resection of bladder tumors followed by different regimens of combined radiochemotherapy achieved comparable results to radical cystectomy in many trials. Those who did not achieve complete remission after induction radiochemotherapy were salvaged by radical cystectomy. Improving the radiotherapeutic window is a challenging issue. In radiotherapy for bladder cancer, uncertainties include set-up errors, patient movement, internal organ movement and volume changes due to bladder filling (both inter- and intrafraction). The advancement in treatment verification procedures in modern radiotherapy and the use of fiducial markers reduces set-up errors, while adaptive radiotherapy could decrease the unnecessary irradiation of normal tissues by tracking bladder volume changes. In addition, new radiotherapeutic techniques, such as intensity-modulated

39www.gsrd.cu.edu.eg

8226 Evaluation of Posteromedial Transdiscal Superior Hypogastric Block After Failure of the Classic Approach

Dina Nabil, MD and Ali A. Eissa, MD

Clin J Pain 2010;26:694–697), (Times New Roman 12 Italic

8227 Presence of Human Herpes Virus 6 (HHV6) in pediatric lymphomas: impact on clinical course and association with cytomegalovirus infection

Samah A Loutfy1,4, Mohamed Fawzy2, Mohamed El-Wakil3, Manar M Moneer3

Virology Journal 7: 287 (2010)

Vol. 6 (2), Oct.2012

radiotherapy and volume-modulated radiotherapy, permit dose escalation to the target without increasing the dose to the

surrounding normal tissues.

Keywords: adaptive radiotherapy ; bladder cancer ; IGRT ; image-guided radiotherapy ; radical radiotherapyradiotherapy techniques ; transurethral resection of bladder tumor ; trimodality treatment TURBT

Historically adjuvant and neoadjuvant radiotherapy in muscle-invasive bladder cancer did not show clear significant benefit over cystectomy alone. Postoperative radiotherapy was unpopular due to the fear of the late intestinal toxicity that may inflect. With the vast advancement in radiation oncology techniques and imaging modalities, these indications had different new paradigm. Locoregional recurrences accounted for a high percentage of failure especially in locally advanced cases. Distant metastases continued to show high percentage in such patients. The new era of modern radiotherapy of conformal, intensity modulated (IMRT), image-guided (IGRT) and adaptive radiotherapy applied to the concept of pre- or postoperative radiotherapy can decrease the locoregional failure and the normal tissue complication probabilities and hence improve the treatment end results. Addition of chemotherapy to the local adjunctive radiotherapy may lead to even better outcome provided that the immediate and late

toxicities are kept at minimal levels.Keywords:

Bladder cancer refers to any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The most common type of bladder cancer begins in cells lining the inside of the bladder and is called transitional cell carcinoma.

This book reviews research in the study of bladder cancer including recent advances in intravesical therapy for non-muscle invasive bladder cancer; molecular and genetic mechanisms in defining distinct genetic pathways of bladder cancer, and molecular proteins in urothelial carcinoma.

8231 Estrogen exposure and bladder cancer risk in Egyptian women

Beverly J. Wolpert, , Sania Amr, Sameera Ezzat, Doa’a Saleh, Iman Gouda, Iman Loay, Tamer Hifnawy, Nabiel N. Mikhail, Mohamed Abdel-Hamid, Min Zhan, Yun-Ling Zheng, Katherine Squibb, Mohamed A. Abdel-Aziz, Mohamed Zaghloul, Hussein Khaled Christopher A. Loffredo

Estrogen Bladder cancer Egypt Epidemiology Risk factors

Objective: To examine associations between reproductive history and urinary bladder cancer in Egyptian women.

Methods:Weused questionnaire data from an ongoing, multicenter case–control study in Egypt. Controls were matched on age and residence area. This analysis focused on female cases with confirmed Urothelial (UC) and squamous cell (SCC) carcinoma of the bladder.

Results: We recruited 779 women (540 controls, 239 cases; >98.0% nonsmokers). Younger age at menopause (<45 y) and older age at first pregnancy (>18 y) were factors significantly associated with increased risk of bladder cancer, even after adjusting for schistosomiasis history and other covariates in the multivariable logistic model; adjusted odds ratio and 95% confidence intervals were 1.98 (1.41, 2.77) and 6.26 (3.46, 11.34), respectively. On the other hand, multiple pregnancies or use of oral contraceptives were associated with decreased

odds of having bladder cancer. Similar associations were

observed with UC and SCC when analyzed separately; however,

the magnitude of association with SCC was lower than with UC.

Conclusion: Our data suggest that early estrogen exposure, or the relative lack of it, plays a role in urinary bladder carcinoma development among Egyptian women

Keywords: Estrogen Bladder cancer Egypt Epidemiology Risk factors

40www.gsrd.cu.edu.eg

8229 The need to revisit adjuvant and

neoadjuvant radiotherapy in bladder cancer.

Mohamed Saad Zaghloul, MD

Expert Rev. Anticancer Ther. 10(10), 1527–1528 (2010)

8230 Bladder Cancer: Etymology, Diagnosis, and Treatments

Mohamed S. Zaghloul

Bladder Cancer: Etymology, Diagnosis, and Treatments

Vol. 6 (2), Oct.2012

Background Zoledronic acid treatment reduces the incidence of

skeletal-related events (SREs) in patients with bone metastases from breast, lung, and urologic cancers including prostate and renal cancer. The aim of this study was to evaluate the effect of zoledronic acid on SREs in patients with bone metastases from bladder cancer.

Patients and methods: Patients with bone metastases from bladder cancer who were receiving palliative radiotherapy were randomized to placebo or zoledronic acid (4 mg intravenous monthly) for 6 months.

Results: The patients (n = 40) were evenly distributed between the two treatment groups, and the baseline demographics of the two groups were similar. The follow up

varied from 8 to 65 weeks (median 24 weeks). Compared with patients receiving placebo, those receiving zoledronic acid had a lower mean incidence of SREs (2.05 ± 1.0 vs 0.95 ± 0.9, respectively), and a larger proportion did not experience an on-study SRE (2 vs. 8 patients, respectively). Zoledronic acid also prolonged the

median time to first SRE compared with the placebo (16 vs. 8 weeks, respectively). Multiple event analysis of SREs revealed that zoledronic acid decreased the risk of SRE development by 59% (hazard ratio 0.413). Zoledronic acid also increased the 1-year survival rate compared with placebo (36.3 ± 11.2 vs. 0%, respectively). Zoledronic acid was generally well tolerated in our patient population.

Conclusions: Zoledronic acid therapy decreased the incidence of SREs and improved the 1-year survival rate of patients with bone metastases from bladder cancer, particularly through its anticancer activity

Keywords: Bisphosphonates _ Bladder cancer _Bone metastasis _ Multiple event analysis _Skeletal-related events _ Zoledronic acid

To date, radical cystectomy has continued to be the treatment of choice for muscle-invasive bladder cancer. It is associated with a 5-year disease-free survival rate ranging from 27–55%. This outcome is significantly worse when reporting upon locally advanced cases. The independent prognostic factors include: tumor stage, grade, pelvic nodal involvement and some other additional factors. Beside the higher reported incidence of distant metastasis, local recurrence either alone or combined with systemic relapse has been shown to be experienced by 23–50% of locally advanced patients – a rate that was much more frequent than previously believed. Nonrandomized trials of preoperative radiotherapy have suggested improved survival rates. However, only one out of the six randomized preoperative trials in the literature published in English has proved to be significant. On the other hand, the only randomized trial and most retrospective studies dealing with postoperative radiotherapy revealed a significant increase in disease-free survival. Late complications of post operative radiotherapy, contrary to former belief, were acceptable and generally depended upon the volume of the irradiated normal tissues and the radiotherapy techniques used. Most of these adjuvant or neoadjuvant reports were performed in the 1970s and 1980s using conventional radiation techniques. Modern radiotherapy, delivering higher doses to the tumor while saving a significant amount of the surrounding normal structure, has not been rigorously tested. However, these techniques have already succeeded in improving treatment end

results in other pelvic tumors.

Keywords : adaptive radiotherapy adjuvant radiotherapy bladder cancer n IGRT neoadjuvant radiotherapy prognostic factor n radical cystectomy n radiotherapy technique

Aim: To compare the accuracy of radiotherapy set-up using an

electronic portal imaging device (EPID) versus megavoltage cone beam computed tomography (MV-CBCT) in paediatric patients. Materials and methods: In total, 204 pairs of EPID and MV-CBCT were carried out for 72 patients in the first 3 treatment days and weekly thereafter. Results: For the whole group, the mean systematic EPID set-up errors were 1.8 (_1.7),

41www.gsrd.cu.edu.eg

8232 A prospective, randomized, placebo- controlled trial of zoledronic acid in bony metastatic bladder cancer

Mohamed S. Zaghloul , Rimoun Boutrus, Hisham, Hisham El-Hossieny, Yasser Abdel Kader, Inas El-Attar, Mohamed Nazmy

Int J Clin Oncol (2010) 15:382–389.(

8233 Adjuvant and neoadjuvant radiotherapy for bladder cancer: revisited

Mohamed Saad Zaghloul

Future Oncology,2010; 6 (7)

8234 Comparison of Electronic Portal Imaging and Cone Beam Computed Tomography for Position Verification in Children

M.S. Zaghloul, A.G. Mousa, E. Eldebawy, E. Attalla, H. Shafik, S. Ezzat

Clinical Oncology 22 (2010) 850 – 861

Vol. 6 (2), Oct.2012

1.6 (_1.3), 1.4 (_1.5) mm and 2.3 (_1.7), 1.6 (_1.3), 2.4 (_1.6) mm for MVCBCT in the longitudinal, lateral and vertical directions, respectively, whereas the mean EPID random errors were 2.0 (_1.7), 1.4 (_1.5), 1.2 (_1.6) and 1.9 (_1.5), 1.5 (_1.3), 2.1 (_1.7) mm for MV-CBCT in the longitudinal, lateral and vertical directions, respectively. For systematic errors of head and neck patients, there was a statistically significant difference in the lateral and vertical directions (P ¼ 0.027, 0.003), whereas in the non-head and neck patients there was a statistically significant difference in the lateral direction only (P ¼ 0.031). In head and neck patients, the mean random errors were significantly different in the vertical and lateral directions, whereas in non-head and neck patients, they were significantly different in the vertical direction only. The larger values alternate between the two modalities.

The systematic and random errors (detected by EPID and MV-CBCT) were significantly correlated in almost all direction in all tumour sites.

Conclusions: The comparison between set-up error in EPID and MV-CBCT was not in favour of any of the two modalities. However, the two modalities were strongly correlated but fairly agreed and the differences between the shifts reported were small and hardly influenced the recommended planning target volume margin.

Keywords: Cone beam CT; EPID; paediatric tumours; PTV margin; radiotherapy position verification; set-up error

8235 Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases

Saad S.Eissa, NormanBlock, Hussein M.Khaled, Sohair H.Shoman, Mehdi Nassiri , Mehrdad Nadji

Journal advanced research, 1: 151-156-2010

Primary enteric-type adenocarcinoma of the urinary bladder is relatively uncommon. We present our experiencewith109 pure, nonurachal cases—the largest series todate.This work was under taken with the aim of describing the immunohistochemical features of adenocarcinoma of the urinary bladder associated withschistosomiasis,illustratingtheirhistologicandimmunohistochemical similarities to colorectal carcinomas. PartialortotalcystectomyspecimensfromacohortofEgyptianandA

mericanpatientswiththe diagnoses of primary adenocarcinoma of the urinary bladder (109cases) were reviewed. Paraffin sections of each tumour were stained using the labelled streptavidin–biotinmethodusingantibodiescytokeratin 20, cytokeratin7 ,CDX2,MLH1, and villin. Clinical follow-upwasavailableforatleast36months.An enteric (colonic) morphology was seen in most tumours ;some with signet ring cells or mucinous elements. Five tumors were composed predominantly of signet ring cells and two demonstrated a pure mucinous morphology . Incaseswhereadjacentnormalmucosawaspresent,23%showedeithercolonicmetaplasia or intestinal-typecystitisglandularis.Furthermore,24%ofenteric-typeadenocarcinomashadassociated villous ortubulovillousadenomaswithorwithoutdysplasia.Cytokeratin20wasexpressedby90%,cytokeratin7by17%,CDX2by100%andvillinandMLH1by76%and48%oftumoursrespectively.Themajorityoftumourspresentedwithanadvancedstageandfollowedanaggressiveclinicalcourse. In conclusion, primary non-urachal enteric type adeno-carcinoma of the urinary bladder is morphologically and immunophenotypically similar–if not identical–to colonic adenocarcinoma.The frequent association of enteric carcinomas of the urinary bladder within testinal metaplasia and/orcolonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas.Keywords: Urinary bladder; Adenocarcinoma; Immunohistochemistry; Carcinogenesis

42www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

October 201103-04 National Cancer Institute3-4-01. Dept. of Clinical Pathology144. Solvent-detergent Filtered (S/D-F) FreshFrozen Plasma and Cryoprecipitate MinipoolsPrepared in A Newly Designed IntegralDisposable Processing Bag SystemM. El-Ekiaby, M. A. Sayed, C. Caron, S. Burnouf, N. El-Sharkawy, H. Goubran, M. Radosevich, J. Goudemand, D.Blum, L. de Melo, V. Souli´e, J. Adam and T. BurnoufTransfusion Medicine, (20): 48–61 (2010) IF: 1.808Solvent-detergent (S/D) viral inactivation was recently adapted to the treatment of single plasma donations and cryoprecipitate minipools. We present here a new process and a new bag system where the S/D reagents are removed by filtration and the final products subjected to bacterial (0・2 μm) filtration. Recovered and apheresis plasma for transfusion (FFP) and cryoprecipitate minipools ( 20 { 400پ mL) were subjected to double-stage S/D viral inactivation, followed by one oil extraction and a filtration on a S/D and phthalate [di(2-ethylhexyl) phthalate (DEHP)] adsorption device and a 0・2 μm filter. The initial and the final products were compared for visual appearance, blood cell count and cell markers, proteins functional activity, von Willebrand factor (VWF) multimers and protein profile by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE). Tri (n-butyl) phosphate (TnBP) was quantified by gas chromatography and Triton X-45 and DEHP by highperformance- liquid chromatography (HPLC). General safety tests were by 6 ・5 mL/kg intravenous injection in rats. The treated plasmas and cryoprecipitates were very clear and the protein content and functionality, VWF multimers and SDS– PAGE profiles were well preserved. TnBP and Triton X-45 were <1 and <25 ppm, respectively, and DEHP (about 5 ppm) was less than it was in the starting materials. Blood cell counts and CD45, CD61 and glycophorin A markers were negative. There was no enhanced toxicity in rats. Thus, plasma and cryoprecipitate can be S/D-treated in this new CE-marked disposable integral processing system under conditions preserving protein function and integrity, removing blood cells, S/D agents and DEHP, and ensuring bacterial sterility. This process may offer one additional option to blood establishments for the production of virally inactivated plasma components.Keywords: Blood establishments; Cryoprecipitate; FFP;Filtration; Plasma; Solvent-detergent; Viral inactivation.

145. Internal Tandem Duplication of FLT3Gene in Egyptian Adult Acute Myeloid andAcute Lymphoblastic LeukemiaNahla M. El Sharkawy and Thoraya M. Abdel HamidJournal of American Science, 6 (9): 344-352 (2010)Background: FLT3 plays an important role in stem cell proliferation, differentiation, and survival. The most common mutation in the FLT3 gene is internal tandem duplication (FLT3/ITD). Several studies have demonstrated that FLT3

mutations are a strong detrimental prognostic factor in AML and ALL. Aim: Our study was designed to evaluate the relative frequency of FLT3/ITD status in adult AML and ALL patients and its possible impact on response to treatment and overall survival. Patients and Methods: This study was carried out on 110 newly diagnosed adult acute leukemia cases including 61 AML and 49 ALL. Bone marrow or peripheral blood samples were collected from patients at diagnosis. All samples were analyzed for mutation in exon 11 of the FLT3 gene using genomic PCR method. FLT3/ITD appears as an extra PCR band (mutant band) in addition to the 133-bp wild band. ALL cases were treated according to the risk adapted chemotherapy protocol while mature B phenotype cases were excluded from the study. AML cases received induction with 3&7 regimen combing Daunorubicin, 45m/m2 IV day 1-3 and cytosine arabinoside100 mg /m2 by continuous infusion from day 1 to 7 as an induction regimen. Evaluation of response was carried out at the end of induction. Results: FLT3/ITD mutant band was found in 21.3 % (13 / 61) of AML cases. The highest frequency of FLT3/ITD was associated with M3 (40%) followed by M5 (37.5%) and M4 (33.3%), less frequent in M2 (13.6%), M1 (13.3%) and none in M0 and M7. In ALL cases FLT3/ITD was detected in (5/44) 10.2%. The highest frequency was associated with precursor B phenotype (11.4%) and less in T- ALL patients (7.1%). No association was detected between the FLT3/ITD on one side and age, gender, high leucocytic count, BM blasts, DNA index or CD34 expression on the other side in either AML or ALL. We could not find statistically significant difference in response to treatment between FLT3/ITD positive and negative cases in either AML or ALL patients. Conclusion: FLT3/ITD in our AML patients was 21.3 % which is comparable to the literature. However in adult ALL it was much higher than that reported in literature. In contrast to the literature we failed to demonstrate a detrimental effect of FLT3/ITD on treatment outcome in adult AML patients. Further study on a large scale is recommended to identify the prognostic impact of FLT3/ITD in adult ALL. Keywords: Prognostic factors; Adult AML and ALL; FLT3.52Vol. 5(2), Oct. 2011www.gsrs.cu.edu.eg

3-4-02. Dept. of Diagnostic Radiology146. Effect of Y-90 SIR-Spheres Therapy forMultiple Liver Metastases in a Variety of TumorsIsis W. Gayed, Hisham Wahba, David Wan, Usha Joseph andRavi MurthyJournal of Cancer Science and Therapy, (2): 043-046 (2010)Objective: To evaluate the outcomes of patients receiving Y- 90 SIR-Spheres in patients with multiple liver metastases from different tumors. Methods: 29 consecutive patients with multiple liver metastases from colorectal (13), Islet cell tumors (9), carcinoid tumors (4) or non-small cell lung cancer (3) who were treated with Y-90 SIR-Spheres between March, 2003 and February, 2006 were included. Only patients who had follow-up radiological exams at our institution were included. Data regarding Y-90 SIR-Spheres dose, lobe of liver treated, and chemotherapy (CTx) administered were collected. Patients’ outcomes were evaluated based on radiological evidence of change in size and number of liver metastases. Results: The

43www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

study population included 8 females and 21 males at a mean age of 60y. The mean Y-90 SIR-Spheres dose administered was 39.8 mCi. Both lobes of the liver, the right lobe only or the left lobe only were treated in 26, 2, 1 patients, respectively. Sixteen patients received Y-90 SIR-Spheres after CTx failure, 5 patients as adjuvant therapy after completion of CTx, 7 patients as concurrent therapy and one patient refused repeat CTx. The mean interval between the last CTx and Y-90 SIR-Spheres was 108 days. Four patients (14%) demonstrated radiological improvement and 9 (31%) were stable for a mean interval of 2.8 mo. after Y-90 SIR-Spheres infusion. Sixteen patients (55%) demonstrated continued progress of liver metastases. Conclusion: Y-90 SIR-Spheres therapy is useful in reducing or stabilizing multiple liver metastases from a variety of tumors. Keywords:Y-90; SIR-Spheres; SIR therapy liver metastases.

3-4-03. Dept. of Medical Oncology147. Treatment of the Pregnant Mother withCancer: A Systematic Review on the use ofCytotoxic, Endocrine, Targeted Agents andImmunotherapy During Pregnancy. Part II:Hematological TumorsHatem A. Azim Nicholas Pavlidis and Fedro A. PeccatoriCancer Treatment Reviews, (36): 110–121 (2010)IF: 5.295Managing pregnant patients with hematological tumors pose even more conflicts compared to solid tumors. Unlike the majority of solid tumors, hematological malignancies are potentially curable; hence it is important to deliver the best treatment options available, which sometimes could be too aggressive to deliver during pregnancy. In part II, we report the results of women with hematological malignancies treated with systemic therapies during the course of pregnancy. Lymphoma, acute leukemia and chronic myeloid leukemia were the most commonly treated. We discuss the safety of the different regimens reported and propose alternatives to standardized approaches in case they pose significant risk to the pregnancy and/or the fetus.Keywords: Leukemia in pregnancy; Lymphoma inpregnancy; Rituximab; Chemotherapy; Safety.

148. Treatment of the Pregnant Mother withCancer: A Systematic Review on the use ofCytotoxic, Endocrine, Targeted Agents andImmunotherapy During Pregnancy. Part I:Solid TumorsHatem A. Azim, Fedro A. Peccatori and Nicholas PavlidisCancer Treatment Reviews, (36): 101–109 (2010) IF: 5.295The association of cancer and pregnancy is increasingly encountered nowadays in clinical practice. Due to the relative rarity of the situation, it lacks a systematized approach. Different systemic therapies are used in managing cancer with uncertainty regarding the potential hazards they could pose on the pregnancy and/or the fetus. We have performed a systematic review of literature to identify all reports addressing cancer patients who were exposed to any of the known systemic therapies during the course of the pregnancy. The results were discussed in two parts; part I addresses pregnant patients with

solid tumors while part I for those with hematological malignancies. In part I, we identified different solid tumors diagnosed and treated during the course of pregnancy. Breast cancer was the most commonly treated followed by ovarian cancer. Other tumors were treated as well including lung cancer, cervical cancer, sarcoma and melanomas. It is important to acknowledge the intent of therapy (palliative vs. curative) and the patients has to be properly counseled to reach an informed decision. We aim to provide a more robust consensus on how to approach these cases and provide a higher degree of evidence to support the safety of applying certain management strategies over the other.

149. Lung Cancer in the Pregnant Woman: toTreat or not to Treat, that is the QuestionHatem A. Azim, Fedro A. Peccatorib and Nicholas PavlidisLung Cancer, (67): 251–256 (2010) IF: 3.140

Lung cancer in pregnancy is a rare situation; however, it is increasingly reported in the past two decades. The association might be more encountered in the coming years due to the rising trends of cigarette smoking among young women and tendency to delay pregnancy to later in life. We performed a literature search without any date or language restriction and identified 44 cases diagnosed and/or treated for lung cancer during the course of pregnancy. Patients had poor post-partum 53 International Publications Awards, Cairo University (IPACU) Medical Sciences Sector outcome with less than one-forth alive at 1 year following delivery. There was a high incidence of metastases to the products of conception reaching 26%. Eight patients were treated with systemic therapies during the course of gestation with normal fetal outcome and no evidence of fetal or placental metastases. Counseling of these patients is very important. Apart from the clinical conflict they pose, some ethical aspects should be taken in consideration. The poor maternal prognosis should be discussed and the patient’s autonomy should be respected to decide whether she wants to keep the pregnancy or not. Keywords: Lung cancer in pregnancy; Gestation; Chemotherapy; Ethical conflict; Placental metastases; Fetal metastases.

150. Simultaneous Targeting of Estrogen Receptor and HER2 in Breast Cancer

Hatem A. Azim and Martine J. Piccart Expert Rev. Anticancer Ther, 10 (8): 1255–1263 (2010)

IF: 2.493

Approximately 50% of HER2-positive breast cancers express estrogen receptor (ER) and these tumors are characterized by short-lived responses to hormonal agents. Preclinical models have shown that dual targeting of ER and HER2 could reverse and delay the development of drug resistance. Two studies (TAnDEM & EGF3008) have recently been published addressing the combined use of an aromatase inhibitor (AI) and an anti-HER2-targeted agent. Both studies showed that the

44www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

combined approach is associated with improvement in response rate and progression-free survival compared with an AI alone with an acceptable toxicity profile. These results would indeed extend the treatment options for patients with ER/HER2-positive metastatic breast cancer. In this article, we discuss how the improved understanding of the complex cross-talk between ER and HER2 has resulted in better clinical outcomes. We analyze clinical evidence regarding the combined use of AIs and anti- HER2-targeted agents. We also touch on possible mechanisms of resistance and ways to improve research in this field. Keywords: Aromatase inhibitors; Cross-talk; Estrogen receptor: HER2; Lapatinib; Resistance; Trastuzumab.

3-4-04. Dept. of Nuclear Medicine

151. False-positive F-18 FDG Uptake in PET/CT Studies in Pediatric Patients with Abdominal Burkitt's Lymphoma

Raef Riada, Walid Omara, Iman Sidhomb, Manal Zamzamb, Iman Zakyc, Magdy Hafezd and Hussein M. Abdel-Dayeme Nucl Med Commun, Doi 10.1007/s00259-009-1276-1279

IF: 1.315

IntroductionIn pediatric patients with abdominal Burkitt’s lymphoma, the involvement of the gastrointestinal tract and abdominal lymph nodes is the main presenting feature of the disease. Chemotherapy is the main treatment modality and could be preceded by surgical excision of the abdominal masses. To achieve cure or long-term disease-free survival a balance has to be struck between aggressive chemotherapy and the probability of tumor necrosis secondary to treatment complicated by acute infections, perforation or intestinal bleeding. F-18 fluorodeoxyglucose-positron emission tomography/computed tomography (F-18 FDG-PET/CT) has been recommended over conventional imaging modalities for the follow-up of these patients and for monitoring treatment response. As the incidences of postchemotherapy complications are high, the positive predictive value of PET/CT studies in these patients is very low and the falsepositive rate is high from acute infections and tumor necrosis. Accordingly, histopathological confirmation of positive lesions on F-18 FDG-PET/CT studies is essential. This is especially important as post-therapy complications might present with nonspecific and nonurgent symptoms. At the same time initiating a second course of salvage chemotherapy is risky. Aim of studyRetrospectively reviewed F-18 FDG-PET/CT studies for 28 pediatric patients with abdominal Burkitt’s lymphoma and diffuse large B-cell lymphoma after their treatment with chemotherapy or surgery. ResultsFour positive studies were found. All had pathological verification and were because of acute inflammation and tumor necrosis and there was no evidence of viable tumor cells. One patient had multiple recurrent lesions in the abdomen after the initial surgical excision and before starting chemotherapy. The incidence of acute complications in this series is 10.7%. ConclusionThis

study confirms the high incidence of tumor necrosis and inflammation after chemotherapy for the abdominal Burkitt’s lymphoma and consequently, the incidence of true-positive F-18 FDG studies is low. This necessitates the need for histopathological confirmation of positive studies. Keywords: Abdominal Burkitt’s lymphoma; F-18 FDGPET/ CT; Pediatric malignant lymphoma; Tumor necrosis.

3-4-05. Dept. of Radiotherapy and Nuclear Medicine

152. Comparison of Dosimetric Characteristics of Siemens Virtual and Physical Wedges for ONCOR Linear Accelerator

Ehab M. Attalla, H. S. Abo-Elenein, H. Ammar and Ismail El-Desoky Journal of Medical Physics, 35 (3): 164-169 (2010)

Dosimetric properties of virtual wedge (VW) and physical wedge (PW) in 6- and 10-MV photon beams from a Siemens ONCOR linear accelerator, including wedge factors, depth doses, dose profiles, peripheral doses, are compared. While there is a great difference in absolute values of wedge factors, VW factors (VWFs) and PW factors (PWFs) have a similar trend as a function of field size. PWFs have stronger depth dependence than VWF due to beam hardening in PW fields. VW dose profiles in the wedge direction, in general, match very well with those of PW, except in the toe area of large 54 Vol. 5(2), Oct. 2011 www.gsrs.cu.edu.eg wedge angles with large field sizes. Dose profiles in the nonwedge direction show a significant reduction in PW fields due to off-axis beam softening and oblique filtration. PW fields have significantly higher peripheral doses than open and VW fields. VW fields have similar surface doses as the open fields, while PW fields have lower surface doses. Surface doses for both VW and PW increase with field size and slightly with wedge angle. For VW fields with wedge angles 45° and less, the initial gap up to 3 cm is dosimetrically acceptable when compared to dose profiles of PW. VW fields in general use less monitor units than PW fields. Keywords: Physical wedge; Virtual wedge; Wedge; Wedge dosimetry.

3-4-06. Dept. of Tumour Biology 153. The Alternative End-joining Pathway for Repair of DNA Double-strand Breaks Requires PARP1 but is not Dependent Upon Microhomologies

Wael Y. Mansour,Tim Rhein and Jochen Dahm-Daphi Nucl. Acids Res, 38 (18): 6065-6077

IF: 7.479

Non-homologous end-joining (NHEJ), the major repair pathway for DNA double-strand breaks (DSB) in mammalian cells, employs a repertoire of core proteins, the recruitment of which to DSB-ends is Ku-dependent. Lack of either of the core components invariably leads to a repair deficiency. There has been evidence that an alternative end-joining operates in the

45www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

absence of the core components. We used chromosomal reporter substrates to specifically monitor NHEJ of single I-SceIinduced- DSB for detailed comparison of classical and alternative end-joining. We show that rapid repair of both compatible and non-compatible ends require Ku-protein. In the absence of Ku, cells use a slow but efficient repair mode which experiences increasing sequence-loss with time after DSB induction. Chemical inhibition and PARP1-depletion demonstrated that the alternative end-joining in vivo is completely dependent upon functional PARP1. Furthermore, we show that the requirement for PARP1 depends on the absence of Ku but not on DNA-dependent protein kinase (DNA-PKcs). Extensive sequencing of repair junctions revealed that the alternative rejoining does not require long microhomologies. Together, we show that mammalian cells need Ku for rapid and conservative NHEJ. PARP1-dependent alternative route may partially rescue the deficient repair phenotype presumably at the expense of an enhanced mutation rate. Keywords: Alternative NHEJ; DSB repair; GFP-based vectors; PARP1; Microhomology.

154. Targeting DNA Double-strand Break Repair: is it the Right Way for Sensitizing Cells to 5-fluorouracil?

El-Awady RA, Saleh EM and Dahm-Daphi J. Anti-Cancer Drugs, 21 (3): 277-287 (2010)

IF: 2.230

Inhibition of the repair of 5-fluorouracil (FU)-induced DNA lesions may improve the response of many tumors to this anticancer agent. Despite the identified associations between DNA strand breaks and the lethality of thymidylate synthase inhibitors, the role of DNA double-strand break (DSB) repair pathways in a cellular response to 5-FU treatment has not been studied yet. Isogenic cell lines defective (irs1SF), wild type (AA8), or reconstituted (1SFK8) in the DSB repair protein XRCC3 were used to investigate the effect of defective DSB repair on the overall sensitivity of cells to 5-FU and to see how targeting DSB repair may affect other cellular responses to 5-FU. Treatment with 5-FU resulted in (i) similar induction of DSB in both cell lines as indicated by the formation of gamma-H2AX (a marker for DSB). The repair of these breaks was complete in AA8 but not in irs1SF cells. (ii) Concentration-dependent reduction in the survival of both cell lines. The AA8 cells were six times more sensitive to 5-FU than the irs1SF cells. (iii) An earlier and more prolonged G(1)/S phase arrest in AA8 compared with the irs1SF cells. (iv) Induction of apoptosis as indicated by sub-G(1) cells and caspase-3 activity in AA8 but not in irs1SF cells. XRCC3 complementation of irs1SF cells restored the wild-type phenotype. This result shows that targeting DSB repair is not always associated with increased sensitivity to DNA damaging agents such as 5-FU because it may affect other cellular responses such as cell cycle regulation and induction of apoptosis. Keywords: Apoptosis; DNA double-strand breaks; DNA repair; 5-fluorouracil, XRCC3.

155. Expression of RAD51, BRCA1 and P53 does not correlate with Cellular Radiosensitivity of Normal Human Fibroblasts

Saleh EM and El-Awady RA. Irish J Med Sci, (2010)

IF: 0.696

Aims: To evaluate the potential role of key DNA repair proteins in the sensitivity of normal human fibroblasts to ionising radiations. Methods: Radiosensitivity of six human fibroblast strains established from skin biopsies of women who had undergone conservative breast surgery and received a curative breast conserving radiotherapy was measured by colony-formation assay. The expression level of RAD51, BRCA1 and p53 proteins were studied using western blot analysis. Results: The six fibroblast strains represent a typical spectrum of normal human radiosensitivity with the surviving fraction measured for a dose of 3.5 Gy (SF3.5) ranging from 0.21 to 0.40. We found that these differences in cell survival did not correlate with the expression of RAD51, BRCA1 nor International Publications Awards, Cairo University (IPACU) Medical Sciences Sector p53 in the tested normal human fibroblast strains. Conclusions: We conclude that measurement of protein expression of the three tested genes (RAD51, BRCA1 and p53) did not reflect sensitivity of normal fibroblasts to IR. Keywords: RAD51; BRCA1; p53; DNA repair; Ionizing

radiation.

46www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

2012, May 3-4. Faculty of National Cancer Institute 3-4-01. Dept. of Anesthesiology and Algology

Objective: Stellate ganglion block is usually performed with the classic anterior paratracheal approach. The anatomy of the stellate ganglion being in close proximity to various critical structures renders a number of complications, which are potentially associated with its blockade. The aim of this study was to assess the analgesic efficacy and safety of a new approach of the stellate ganglion block using an oblique fluoroscopic view. Methods: Fifty patients with postmastectomy pain syndrome were randomly allocated into 1 of 2 groups: the anterior paratracheal stellate block group and the oblique fluoroscopic stellate blockgroup. Four blocks were performed for each patient using the same approach each time. The results were evaluated in terms of pain intensity as assessed by the visual analog scale score, morphine consumption, and allodynia surface area (in cm2). Patient satisfactionscore (PSS), skin temperature, side effects, and complications were recorded and compared between the 2 studied groups after each block had been performed. Results: The mean visual analog scale score, daily morphine consumption, and areas of allodynia were significantly decreased and the PSS was significantly increased after each block and for up to3 months after the last block in both the groups. However, there were no statistically significant differences between the 2 groups at the same study period apart from PSS, which was statistically more significant in group oblique at certain times. The incidences of side effects were significantly more in group classic than in group oblique. Conclusions: The oblique fluoroscopic approach of the stellate ganglion block is as effective as the anterior paratracheal approach but is safer and more satisfactory to the patients. Keywords: Stellate ganglion block; Techniques of stellate

ganglion block; Postmastectomy pain. 3-4-02. Dept. of Biostatistics and Cancer Epidemiology

Purpose: With the increasing emergence of multiresistant pathogens, better understanding of these infections is necessary. The aim of the present study was to evaluate the risk factors associated with isolating a multiresistant organism (MRO) from a positive blood culture in pediatric cancer patients with febrile neutropenia (F&N), and to study its impact on clinical course and outcome of febrile episodes. Patients And Methods: The association between MRO with underlying malignancy, age, disease status, hospitalization during episode, absolute neutrophil count, absolute monocyte count, clinical foci of infection, and pathogens isolated was assessed in bacteremic pediatric cancer patients. The MRO phenotype was defined as diminished susceptibility to ≥3 of the broad spectrum antibody classes. Results: Among 239 episodes of blood stream infections (BSI), Gram-positive, and Gram-negative organisms were detected in 180 (75%), and 59(25%) episodes, respectively; with 38% of isolates showing multiresistance (n = 92). Significant risk factors (P < 0.05) for MRO were hospitalization, Gram-negative organisms, presence of clinical focus of infection, reduced ANC, prolonged duration of neutropenia, and previous intake of antibiotics. Of the episodes with prolonged duration of fever extending for more than 7 days 62% (64|93) were associated with a multiresistant phenotype, while it accompanied 72% (18|25) of the cases with an unfavorable outcome; P-value <0.001. Conclusion: Isolation of MRO is more likely to be associated with a prolonged course and an unfavorable outcome. Continuous multidisciplinary surveillance of BSI is warranted to develop strategies for antimicrobial resistance control.

Previous studies showed that non-cycling cells have a higher multidrug resistance (MDR) expression, which may be down-regulated by proliferation induction.Triggering these cells into proliferation down-regulates high MDR expression. The aim of this study was to determine the expression of P-glycoprotein (PGP) and cell cycle parameters (cyclin D1 and Ki-67) in acute lymphoblastic leukemia (ALL) at diagnosis, and to evaluate the correlation between the expressions of each marker, and the clinical significance of such expression with response to induction chemotherapy and overall survival. A total of 78 newly diagnosed ALL patients were enrolled in our study. PGP, cyclin D1 and Ki-67 were determined by flow cytometry. PGP expression was encountered in 10/78 (12.8%) of ALL cases.

47www.gsrd.cu.edu.eg

524. Fluoroscopic Stellate Ganglion Block for Postmastectomy Pain: A Comparison of the Classic Anterior Approach and the Oblique Approach Dina Nabil Abbas, Ekramy M. Abd elGhafar,Wael A. Ibrahim and Azza F.Omran Clin J Pain, 27:207–213 (2011) IF: 3.114

525. Antibiotic Resistance Is Associated With Longer Bacteremic Episodes and Worse Outcome in Febrile Neutropenic Children With Cancer Hadir A. El-Mahallawy, Mohamed El-Wakil, Manar M. Moneer and Lobna Shalaby Pediatr Blood Cancer, 57:283–288 (2011) IF: 1.948

526. Expression of P-glycoprotein, Cyclin D1 and Ki-67 in AcuteLymphoblastic Leukemia: Relation with Induction Chemotherapyand Overall Survival Ghada M. Elsayed, Manar M. Ismail and Manar M. Moneer Indian Journal of Hematology & Blood Transfusion,27 (3): 157-163 (2011)

Vol. 6 (2), Oct.2012

Cyclin D1 and Ki-67 were expressed in 16/77 (20.6%) and 27/76 (34.6%) of ALL cases, respectively. None of the parameters were associated with response to induction chemotherapy and overall survival. Based on the current analysis, we conclude that a joint immunophenotypic evaluation of PGP and cell cycle parameters like that adopted in this study is unlikely to reveal mechanisms of multidrug resistance associated with the clinical outcome. Keywords: P-gp; Cyclin D1; Ki-67; Acutelymphoblastic leukemia (ALL); Multidrug resistance (MDR).

Background: Hepatocellular carcinoma (HCC) is a major contributor to cancer incidence and mortality. HCC is a highly fatal disease and is the third leading cause of death from malignancy worldwide. The aim of the study was to determine long-term survival and prognostic factors predictive of the overall survival of HCC patients at the National Cancer Institute (NCI), Cairo University. Patients and methods: A prospective study was conducted on a cohort of 212 HCC patients attending to the medical oncology clinic at the National Cancer Institute (NCI) during the period from July,1, 2007 till August, 31,2008 and they were followed up by phone till November 7th, 2010. Results: The study revealed that 1-year, 2-year, 3-year survival rates of HCC patients were 26.9%, 9.4%, 5.0% respectively, and median overall survival was 6.3 months (95% CI 5.4-7.2). Multivariate analysis revealed that independent predictors of poor survival were pretreatment presence of extrahepatic metastasis and ascites, and not receiving radiofrequency ablation (RFA) as a treatment modality. Conclusion: The study concludes that most HCC patients at NCI presented at a late stage and their survival was poor. Preserved liver function, non-metastatic presentation of the hepatic tumor and receiving RFA as a treatment modality are associated with good survival of HCC patients. Keywords: Hepatocellular carcinoma; Prognosis; Survival; Hepatitis C virus; Smoking.

The aim of this study was to assess smoking behavior of medical workers in the National Cancer Institute (NCI), their knowledge and attitude towards smoking. This is a cross-sectional survey with anonymous selfadministered questionnaires for physicians and nurses. It included three sections; 1) demographic data, 2) questions about knowledge of smoking hazards, religious and lawful aspects and 3) questions regarding smoking status and attitude towards quitting and prohibiting smoking in work and public places. Participants were 246; 185 responded (75.2%). Smokers constituted 25.4% of the sample. Responding current smokers were 37. The majority of smokers reported previous trials to quit, mainly due to health concern (73.3%). All workers know that smoking is harmful to health, the majority were positive about the hazard of passive smoking as well. Ever-smokers showed a negative attitude towards total prevention of smoking at workplace; however, current smokers react positively to smoking restriction in work and public places, about 2/3 stop immediately when confronted by a stop smoking sign. Twentyseven workers (73%) reported less smoking in response to restriction. A large percent (73%) smoke in presence of nonsmokers, however nearly 92% respond to a colleague's demand to stop smoking. It is concluded that smoking remains a common habit among medical works in the NCI in spite of having a good knowledge about its hazards and direct contact with smoking victims. We should search for the suitable approach for this category of smokers to motivate them to quit other than talking about health hazards.

Keywords: Smoking; Knowledge; Attitude; Medical workers. 3-4-03. Dept. of Cancer Biology

Abstract The activity of the α-L-fucosidase (AFU) enzymerepresents an excellent test for diagnosis of hepatocellularcarcinoma (HCC) and fucosidosis recognized ininborn disorder of metabolism and increases the sensitivityof detection to 95.5% in patients with HCC. Therefore, thedetermination of the activity of AFU enzyme is veryimportant and can be used as a screening tool for the earlydiagnosis of tumors for HCC patients. A simple, accurate,and sensitive potentiometric method was developed formeasuring the activity of AFU. The method was based uponmeasuring the concentration of 2-chloro-4-nitrophenol (2-

48www.gsrd.cu.edu.eg

527. Prognostic Factors for Survival of Patients with Hepatocellular Carcinoma in National Cancer Institute, Cairo University Maissa K Noaman, Nargis A Labib, Ghada N Radwan, Othman M Mansour, Manar M Moneer and Inas A Elattar Journal of American Science, 7 (9): 831–839 (2011)

528. Smoking Behavior, Knowledge and attitudes among Medical Workers in the National Cancer Institute, Cairo University Manar M. Moneer, Maissa K. Noaman and Nargis A. Labib Journal of American Science, 7 (6): 1059–1064 (2011)

529. Potentiometric Determination of Α-Lfucosidase Enzyme by using2-Chloro-4nitrophenol-Rhodamine Bionpair Chemical Recognition in PVC Membrane Sensor Abdelhameed M. Othman, M. E. El-Houseini, Mohamed S. El-Sofy and Hassan Y. Aboul-Enein Anal Bioanal Chem, 400:787–795 (2011) IF: 3.841

Vol. 6 (2), Oct.2012

chloro-4-NP) using a 2-chloro-4-NP-rhodamine B ion pairin a PVC membrane sensor. The electrode shows a linear,reproducible, and stable potentiometric response with an anionic Nernstian slope of −51.13±0.6 mV/decade over awide range of concentrations 10−5–10−2 M and a detectionlimit of 1.0×10−6 M of 2-chloro-4-NP. The membrane exhibits a fast response time of 30 s, over a pH range of4.0–6.5. The selectivity coefficients indicate excellentselectivity for 2-chloro-4-NP over a number of interfering species, e.g., chloride, nitrate, sulfate, chromate urea,albumin, glucose, uric acid, and total protein. The preparedsensor has been used successfully for the determination of 2-chloro-4-NP produced from the hydrolysis of 2-chloro-4-NP-α-L-fucopyranoside substrate. It was also applied for thedetermination α-L-fucosidase enzyme of 33 serum samplesof healthy subjects and patients. The average recoveries±RSD for the healthy subjects, cirrhosis of chronic hepatitis Cand B, and HCC serum samples were 102.6±1.01%, 101.5±0.95%, and 100.1±1.1%, respectively. The results obtained are in good agreement with those obtained by standardmethods. Keywords: Rhodamine B (Rd); Potentiometry; PVmembrane sensor; α-L-Fucosidase enzyme (AFU).

The fragile histidine triad gene (FHIT) is a candidate tumor suppressor gene at chromosome 3p14.2. Deletions in FHIT gene were reported in different types of cancer including breast cancer. In this study, we investigated the loss of heterozygosity (LOH) incidence that target FHIT genomic structure and chromosome 3p in cancerous and pre-neoplastic lesions of Egyptian breast patients. Genomic DNA was isolated from tumor tissues and their normal counterparts of 55 Egyptian patients diagnosed with breast cancer and 11 patients diagnosed with preneoplastic breast lesions. LOH was detected in 51% of breast cancer cases in at least one microsatellite marker of the four investigated markers. While, none of the markers showed LOH among the pre-neoplastic breast lesions. We also observed a significant association between LOH and invasive ductal carcinoma (IDC) histopathological type while no association observed between LOH and patients’ age, tumor grade, or lymph node involvement. We also investigated FHIT gene expression profiles in breast cancer using Oncomine database. We found that FHIT is significantly reduced in all investigated studies. We conclude that, FHIT is underexpressed

in breast cancer tissues compared to their normal counterparts due to the extensive allelic loss that is observed in its gene structure. Keywords: FHIT; LOH; Chromosome 3p; Breast

cancer.

The only hope for effective treatment of liver cancer lies in early detection or screening for populations who are at high risk for developing liver cancer. This study was designed to study the levels of a collection of biochemical markers in the sera of patients suffering from hepatocellular carcinoma (HCC) and its predisposing diseases. The ultimate aim is to investigate their diagnostic impact in the early detection of HCC and discriminate from benign liver diseases. The study was carried out on 217 individuals divided into the following groups: Group 1: Normal controls, Group 2: Schistosomal patients (Schist), Group 3: Hepatitis B patients (HBV), Group 4: Hepatitis C patients (HCV), Group 5: Cirrhotic patients (Cirr), and Group 6: Hepatocellular carcinoma patients (HCC). The last group was further subdivided into the following subgroups: a – HCC alone; b – HCC on top of schistosomiasis; c – HCC on top of HBV; d – Hepato-cellular carcinoma on top of HCV; e – HCC on top of cirrhosis. Their sera were subjected to a quantitative determination of the tumour necrosis factor-alpha (TNF-a), epidermal growth factor and its receptor (EGF and EGFR), glutathione-S-transferase alpha (GST-a), iron, ferritin, transferrin, alpha-1-antitrypsin (a1AT) and alpha-fetoprotein (aFP). The results of this study indicate that it is advisable to determine a panel of markers composed of aFP, TNF-a and GST-a to confirm diagnosis of HCC and distinguish it from other benign liver diseases. Keywords: Liver diseases; TNF-a; EGF; EGFR; GST-a and aFP.

Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC) and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR) occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has

49www.gsrd.cu.edu.eg

530. FHIT Gene and Flanking Region on Chromosome 3p are Subjected to Extensive Allelic Loss in Egyptian Breast Cancer Patients Heba M. S. Ismail, Amina M. Medhat, Amr M. Karim and Nadia I. Zakhary Molecular Carcinogenesis, 50 (8): 625-34 (2011) IF: 3.265

531. Impact of different biochemical markers in serum of patients with benign and malignant liver diseases Nadia I. Zakhary, Mahmoud M. El-Merzabani, Nagwa M. El-Sawi, Saleh M. Saleh, Manar M. Moneer and Ragaa H. Mohamad Journal of Advanced Research, 2 (1): 49-55 (2011) IF: 3.00

532. Chronic Hepatitis C Genotype-4 Infection: Role of Insulin Resistance in Hepatocellular Carcinoma Amal A Mohamed, Samah A Loutfy, James D Craik, Abdel Gawad M Hashem and Ibrahem Siam Virology Journal, 8: 496 (2011) IF: 2.546

Vol. 6 (2), Oct.2012

the highest reported rates of HCV infection (predominantly genotype 4) in the world; this study investigated effects of HCV genotype-4 (HCV-4) on prevalence of insulin resistance in chronic hepatitis C (CHC) and HCC in Egyptian patients. Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples. HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p=0.23). Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p<0.001). Conclusions. IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development. Keywords: Hepatitis C; HCV-4; Insulin resistance; Fibrosis; Hepatocellular carcinoma.

Mutations in the mitochondrial genome (mtDNA) are associated with different types of cancer, specifically colorectal cancer (CRC). However, few studies have been performed on precancerous lesions, such as ulcerative colitis (UC) lesions and adenomatous polyps (AP). The aim of this study was to identify mtDNA mutations in the cancerous and precancerous lesions of Egyptian patients. An analysis of the mutations found in six regions of the mtDNA genome (ND1, ND5, COI, tRNAser, D-loop 1, and 2) in 80 Egyptian patients (40 CRC, 20 UC, and 20 AP) was performed using polymerase chain reaction–single-strand conformational polymorphism techniques and followed up by direct sequencing. The overall incidence of mutations was 25%, 25%, and 35% in CRC, UC, and AP cases, respectively. Although there was no common mutation pattern within each group, a large number of mutations were detected in the D-loop region in all of the groups. Some mutations (e.g., T414G) were

detected repeatedly in precancerous (UC and AP) and cancerous lesions. Mutations detected in patients with CRC were predominantly found in the ND1 gene (40%). Our preliminary study suggests that Egyptian patients with CRC have a large number of mtDNA mutations, especially in the D-loop region, which have not been previously reported. Mutations in the mtDNA of precancerous lesions (i.e., AP and UC) may contribute to transformation events that lead to CRC. Keywords: Mitochondrial Mutations; CRC; Tumor biology;

D-Loop.

Hypermethylation at the promoter region is an important epigenetic mechanism underlying the inactivation of tumor suppressor genes and frequently occurs as an early event in the development of different types of cancer including colorectal carcinoma (CRC). The aim of the present study is the detection of methylation status for some tumor suppressor genes including RASSF1A, MGMT, and HIC-1 in both cancerous and precancerous lesions of colorectal mucosa to evaluate the possibility of developing epigenetic biomarker for early detection of Egyptian CRC. Tissue biopsy was collected from 72 patients (36 CRC, 17 adenomatous polyps, and 19 ulcerative colitis), and in addition, adjacent normal-appearing tissues were collected as control. Promoter hypermethylation status for RSSAF1A, MGMT, and HIC-1 genes was detected after isolation of genomic DNA from the tissues samples using methylation-specific PCR technique. High frequency of methylation at MGMT, RASSFA, and HIC-1 was detected in CRC patients (25%, 47.2%, and 41.7% respectively). The highest methylation detected in adenomatous polyps patients was in MGMT gene (47.1%) followed by 35.3% for HIC-1 and only 5.9% for RASSF1A gene. HIC-1 gene exhibited highest frequency of methylation in ulcerative colitis patients (57.8%) whereas it was 26.3% for both RASSF1A and MGMT genes. A nonsignificant association was recorded between the methylation status in different genes examined with the clinicopathological factors except the association between methylation at RASSF1A gene with gender (p=0.005), and it was significant. In conclusion, aberrant hypermethylation at promoter region of RASSFA, MGMT, and HIC-1 genes is involved in Egyptian CRCs. Hypermethylation of MGMT and HIC-1 genes plays an important role in the initiation of disease especially ulcerative colitis-carcinoma pathway. Keywords: RASSF1A; MGMT; HIC-1; Colorectal cancer; Methylation.

50www.gsrd.cu.edu.eg

533. Mutational Hotspots in the Mitochondrial D-Loop Region in –Cancerous and Precancerous Colorectal Lesions in Egyptian Patients Abdel Meguid Kassem, Nadia El-Guendy, Marwa Tantawy, Hala Abdelhady, Akmal El-Ghor and Abdel Hady Abdel Wahab DNA and Cell Biology, 30: 899-906 (2011) IF: 2.159

534. Promoter Hypermethylation Of RASSF1A, MGMT, and HIC-1 Genes in Benign and Malignant Colorectal Tumors Abouzeid HE, Kassem AM, Abdel Wahab AH, El-mezayen HA, Sharad H and Abdel Rahman S Tumor Biology, 32: 845-852 (2011) IF: 2.026

Vol. 6 (2), Oct.2012

Hepatocellular carcinoma (HCC) is one of the most aggressive cancers worldwide. In Egypt, the disease is usuallydetected in an advanced stage at which no treatment may be effective includingsurgery. Early detection of the disease is thusan important goal allowing the patient to be treated before the enlargement of the tumor or its metastasis to distant organs.Tumor markers are serological agents which serum level may be useful in predicting the presence of the tumor at early stages.Alpha fetoprotein (AFP) which is the golden marker for HCC is of low sensitivity, therefore, additional markers such as alpha-L-fucosidase (AFU), transforming growth factors alpha and beta (TGF-α and TGF-β) and interleukin-8 (IL-8) are suggested tobe simultaneously evaluated in order to enhance the detection of HCC. A total of 96 patients with different liver diseases suchas HCC, hepatitis C virus (HCV), hepatitis B virus (HBV) and cirrhotic patients are included in this study. Sixteen healthyvolunteers are used as a control group. In patients with HCC each of AFP, AFU, TGF-α and TGF-β recorded significantly higherlevels than the other patient groups and controls. HCC patients recorded significantly lower level of IL-8 compared to the otherpatient groups but significantly higher than the control. For AFP, AFU, TGF-α, TGF-β and IL-8, at the optimal cut-off values(obtained from the receiver operating characteristic (ROC) curves), the calculated sensitivities are 46%, 72.97%, 67.56%, 54.05%and 83.8%, respectively. The simultaneous evaluation using all of the suggested markers resulted in increasing the sensitivity upto 100%. It thus recommended that, if patients with cirrhosis, as high risk patients, are subjected to regular examination usingthese markers in addition to AFP, HCC may be detected by 100% sensitivity in an early stage and as a consequence an effectivetreatment can be achieved. Keywords: AFP; AFU; TGF-α; TGF-β; IL-8; HCC; HCV; Biomarkers.

Background: Genotoxicity and cytotoxicity of anticancer drugs to the normal cells is the major problem in cancer therapy and engender a risk of inducing secondary malignancies. A dose of anticancer drug which is sufficient to kill tumor cells is often

toxic to the normal tissue and lead to many side effects, which in turn . limited treatment efficacy . Many epidemiological studies have suggested that midcinal plants can play a vital role in inhibiting genotoxicity and carcinogenicity of anticancer drugs to normal cells. Materials and Methods: Lentinus edodes a Chinese edible and medicinal mushroom was grown using submerged culture on different standard liquid media and different food wastes by products. Shiitake broth medium was the medium that showed the maximum biomass for both tested strains. Crude extract of L. edodes mycelia was tested in this study In vitro and in vivo. The in vitro cytotoxic activity of the crude extracts of mycelia of the two strains were examined on human breast cancer (MCF7) cell line using trypan blue exclusion assay and MTT cytotoxicity assay. Result and Discussions: The results showed that the crude extract of Lentinus edodes LC2141 inhibited the proliferation of MCF7 at high concentration with IC50 178.8μg/ml while Lentinus edodes LC202 extract inhibited the proliferation of MCF7 at high concentration with IC50 94.025μg/ml. Cytotoxicity of the crude extracts was tested also against EAC by using trypan blue exclusion assay. Viability increased by decreasing concentration. In vivo experiments, group treated with crude extract of Lentinus edodes LC2141 showed a decrease in tumor size while 4 out 9 mice showed complete tumor regression. Group treated with crude extract of Lentinus edodes LC202 showed a decrease in tumor size while 3 out of 9 mice showed complete tumor regression. The combination between the two crude extracts showed a decrease in tumor size but there was no mice showed complete tumor regression. Keywords: Lentinus edodes Fungi; Human Cancer cell lines; Experimental

Animals ged culture; Antitumor activity.

This study aimed to investigate the antitumor effects of Ecbalium elaterium (squirting cucumber) (Cucurbitaceae) fruit juice and some fruit extracts as well as bee honey separately and in mixture. The fruit juice of E. elaterium, which is found to be rich in cucarbitacins, was selected for further evaluation of antitumor activity on the bases of a phytochemical study by thin layer chromatographic technique (TLC). The antitumor effects of the fruit juice and bee honey (separately and in mixture) were assessed for human brain tumor cell line (U251) using trypan blue exclusion assay for evaluating cytotoxicity, and H3-thymidine assay for estimating DNA synthesis. ELISA

51www.gsrd.cu.edu.eg

535. Serological Biomarkers of Hepatocellular Carcinoma in Egyptian Patients Sarmad F. El-Tayeh, Tarek D. Hussein, Motawa E. El-Houseini, Mahmoud A. Amer, Mamdooh El-Sherbini and Wael M. Elshemey Disease Markers, 31: 1–9 (2011) IF:1.723

536. Antitumor Activity Induced by Crude Extract of Lentinus edodes Fungi in Human Cell Lines and Experimental Animals Wafaa Abdallah Ahmed Journal of American Science (2011)

537. Antitumor Effect of Honey and Squirting Cucumber Fruit Juice Mixture on Glioblastoma Cells in Vitro Nagla El-Sayed,Motawa El-Houseini,Mohamed Ali, Nagwa Shalaby, Atef Hanna and Hanaa Rady International Journal of Biomedical and Pharaceutical Sciences, 5 (1): 12–17 (2011)

Vol. 6 (2), Oct.2012

technique for measuring cell cycle regulation and the evaluation of the effects on metastasis and angiogenesis were also achieved. Results suggested that honey did not inhibit tumor cell growth through cyclin D1, P21 regulation or cell number reduction but through a significant inhibition of DNA synthesis. Results showed that E. elaterium fruit juice significantly down regulated P21, up-regulated cyclin D1, decreased cell number and inhibited DNA synthesis. Mixing of honey with E. elaterium fruit juice decreased the cytotoxicity induced by the latter and produced intermediate inhibition of DNA synthesis and down regulation of P21. All treatments inhibited MMP2 and MMP9. Thus, honey was able to reduce the cytotoxic effect of E. elaterium juice on glioblastoma cells enhancing its ability of inhibiting DNA synthesis and they acting together as antiangiogenic and antimetastatic agents. Keywords: Angiogenesis; Cucarbitacins; Cyclin; D1; MMP; P21.

Hepatocellular carcinoma (HCC), one of the most common malignancies worldwide, is highly resistant to standard therapy. Hepatocellular carcinoma (HCC), which are the most health-threatening conditions drawing considerable attention from medical professionals and scientists. While liver surgery is not suitable in many of the HCC cases, patients are mostly given palliative support cares or transarterial chemoembolization or systemic chemotherapies. However, HCC is well known to be a highly chemoresistant tumor, and the response rate is <10–20%. To this end, alternative medicines are being actively sought from other sources with hopes to halt the disease's progression or even eliminate the tumors. In this work, we discuss our findings and trial studies of some semisynthetic and natural compounds on human HCC cell line. The effect of Vit. E, Corn Oil, t-BHQ and HMBA) against Hep-G2 cells was assessed using MTT assay to investigate cytotoxcity and cell proliferation .Flow cytometeric analysis was used for measurement apoptosis, nicrosis and cell cycle analysis. The results revealed that the treatment of Hep-G2 cells with Vit. E, corn oil, HMBA and TBH dramatically inhibited the cell growth in a dose dependent manner, with IC50 values of 4.48 , 3.97, 3.35 mM and 350.02 µM, respectively. Flow cytometric analysis was performed. The growing cells were treated with IC50 value of different investigated compounds for different intervals (6 and 12 hrs). The untreated cells showed the expected pattern for continuously growing cells, whereas the cells treated with

HMBA and TBH for 12 hrs showed a progressive accumulation in the S phase and G2/M phase of the cell cycle correlating with decreased number of cells in the G0/G1 phase. Meanwhile, Vit. E and Corn oil treated cell showed a progressive accumulation in the Go/G1 phase. The treatment of HMBA showed highest induction of apoptosis followed by TBH, vit. E and the lowest induction of apoptosis was corn oil. It is concluded that the cytotoxicity of semisynthetic compounds (HMBA & TBH) has direct effect on the liver cells represented by the effects on the cell cycle and apoptotic mechanism while natural compounds (vit. E & corn oil) has less effect by the two mechanisms than other tested compounds but still has cytotoxic effect. Keywords: Apoptosis; Necrosis; Hepatocellular carcinoma; Malignancies; Chemoembolization.

Fragile histidine triad (FHIT) gene encodes a putative tumor suppressor protein. Loss of Fhit protein in cancer is attributed to different genetic alterations that affect the FHIT gene structure. In this study, we investigated the pattern of homozygous deletion that target the FHIT gene exons 3 to 9 genomic structure in Egyptian breast cancer patients. We have found that 65% (40 out of 62) of the cases exhibited homozygous deletion in at least one FHIT exon. The incidence of homozygous deletion was not associated with patients’ clinicopathological parameters including patients’ age, tumour grade, tumour type, and lymph node involvement. Using correlation analysis, we have observed a strong correlation between homozygous deletions of exon 3 and exon 4 (P<0.0001). Deletions in exon 5 were positively correlated with deletions in exon 7 (P<0.0001), Exon 8 (P<0.027), and exon 9 (P=0.04). Additionally, a strong correlation was observed between exons 8 and exon 9 (P<0.0001).We conclude that FHIT gene exons are homozygously deleted at high frequency in Egyptian women population diagnosed with breast cancer. Three different patterns of homozygous deletion were observed in this population indicating different mechanisms of targeting FHIT gene genomic structure.

52www.gsrd.cu.edu.eg

538. Induction of Apoptosis, Necrosis and Differentiation in hepG2 Cell Line (Comparison Between Natural and Synthetic Products) Wafaa A.Ahmed, Farid A. Abu Bedair, Abd El Hameed O.M and

Nasser E.A. Nature and Science, 9 (7): 62-73 (2011) IF: 0.500

539. Multiple Patterns of FHIT Gene Homozygous Deletion in Egyptian Breast Cancer Patients Heba M. S. Ismail, AminaM.Medhat, Amr M. Karim and Nadia I. Zakhary International Journal of Breast Cancer, (2011)

Vol. 6 (2), Oct.2012

Objective: This work is designed to study the possible role of chronic inflammation induced by E. coli in the urinary bladder of rats, the protective role of soybean flour, in addition to the role of oxidative and nitrosative stresses during bladder carcinogenesis. Material & Methods: This study was done on one hundred and fifty adult male albino rats (50 - 60 gm) that divided into five groups; a) Normal control group, b) Dibutyl amine and sodium nitrate treated group, c)E.Coli treated group, d) Dibutyl amine and sodium nitrate treated group plus E. coli, and e) Dibutyl amine and sodium nitrate treated group plus soy bean flour. Survival rate and histopatholgical changes during the period of treatment were recorded. Level of malondialdhyde, glutathione, catalase, hydrogen peroxide, Total anti-oxidant capacity and nitric oxide were measured. RNA extracted from bladder tissues was determined in addition to P16 level and caspase-3 expression. Results: Survival analysis showed a significant decrease (p< 0.001) in E.Coli and dibutyl amine plus sodium nitrate treated groups in comparing with the normal and other treated groups. Also, E. coli infection in the bladder tissues increases the carcinogenic ability of nitrosamine precursors, and enhances oxidative and nitrosative stresses via increasing levels of nitric acid, hydrogen peroxide and malondialdhyde. Regarding the molecular changes, extra bands have been found in E. coli and E. coli + carcinogen treated groups approximately at 16-18KD which are not present in the other groups. Conclusion: Bacterial infection of the urinary bladder may play a major additive and synergistic role in bladder carcinogenesis. Our results have also shown that soy bean flour may have a protective action during induction of urinary tumors. Keywords: Bladder carcinogenesis; E.Coli; Soybean; DBA; P16.

Lentinus edodes a Chinese edible and medicinal mushroom was grown using submerged culture on different standard liquid media and different food wastes by products. Shiitake broth medium was the medium that showed the maximum biomass for both tested strains. The biomass obtained from cultivation

on all tested media was extracted with ethanol to obtain crude extract that tested for its biological activity. Also, SM broth medium showed the highest crude extract yield for the two strains. Some physiological factors were studied to optimize the conditions for cultivation on SM broth medium for maximum biomass and crude extract yield. Although recent studies have demonstrated that L. edodes separate compounds can inhibit the proliferation of cancer cells In vitro and in vivo, crude extract of L. edodes mycelia was tested in this study In vitro and in vivo. The Invitro cytotoxic activity of the crude extracts of mycelia of the two strains were examined on human breast cancer (MCF7) cell line using trypan blue exclusion assay and MTT cytotoxicity assay. The results showed that the crude extract of Lentinus edodes LC2141 inhibited the proliferation of MCF7 at high concentration with IC50 178.8ìg/ml while Lentinus edodes LC202 extract inhibited the proliferation of MCF7 at high concentration with IC50 94.025ìg/ml. Also, The treatment of Hep-G2 cells with different concentrations of ethanolic extract of both Lentinus edodes LC2141 and Lentinus edodes LC202 dramatically inhibited the cell growth in a dose-dependent manner, with high IC50 values of 953.1ìg/ml and 1868.3ìg/ml, respectively. Immunomodulating activity of the tested extracts was determined on normal and breast cancer patient lymphocyte using MTT and trypan blue exclusion assays. The treatment of lymphocyte with different concentrations of the crude extract showed an increase in lymphocyte proliferation by increasing concentration (dose dependant). Keywords: Lentinus edodes; Ethanolic crude extract; Submerged culture; Antitumor activity.

Telomerase is an attractive molecular target for cancer therapy because it is present in most malignant cells but is undetectable in most normal somatic cells. Human telomerase consists of two subunits, an RNA component (hTR) and a human telomerase reverse transcriptase component (hTERT). Small interfering RNA (siRNA), one kind of RNA interferences, has been demonstrated to be an effective method to inhibit target gene expression in human cells. We investigated the effects of siRNA targeting both hTERT mRNA and protein expression on the inhibition of proliferation and growth of human breast carcinoma cells (MCF-7) and liver carcinoma cells (HEPG-2). Here we used two siRNAs sequences (siRNA#1 and siRNA#2) that differentially target hTERT. Our results revealed that

53www.gsrd.cu.edu.eg

540. Role of Urinary Tract Bacterial Infection in the Process of Bladder Carcinogenesis (Molecular and Biochemical Studies) Abeer M. Ashmawey, Waleed S. Mohamed, Ibrahim M. Abdel-Salam, Saad M. El-Gendy, Ali I. Ali and Abdelbaset A. El-Aaser Asian journal of medical science, 2: 31-40 (2011)

541. Studies of Ethanolic Extract from Lentinus edodes on Different Cell Lines and Lymphocytes Separated from Cancer Breast Patients Ahmed, W.A., Osman, M.E., Khattab, O.H., Hassan, F.R.H. and El-Henawy, H.E. Cancer Biology, 1 (2): 1-9 (2011)

542. siRNA Mediated-hTERT Knockdown Impedes Proliferation of Mammalian Cancer MCF7 and HepG2 Cells Abeer Mostafa El-Sayed Ashmawy, Esam Khatab, Wael Bakry Abd El-Aziz Anbar, Bakry Mohamed Haroun and Sabry Mohamed Shaarawy Journal of American science, 7 (3): 179-186 (2011) IF: 0.500

Vol. 6 (2), Oct.2012

treatment of MCF7 and HepG2 cells with either of hTERT siRNAs resulted in significant decrease in both mRNA (p<0.05) and hTERT protein expression (p<0.05). Summary, our results clearly demonstrate that siRNA mediated knockdown of telomerase has efficiently suppressed proliferation rate of MCF7andHepG2cells. From these findings, we propose that targeting telomerase using siRNA might be a rational approach in cancer therapy. Keywords: Telomerase knockdown;

Proliferation; siRNA; Liver carcinoma; Breast carcinoma. 3-4-04. Dept. of Medical Oncology

Background: EORTC study 08021/ILCP 01/03 evaluated the role of consolidation gefitinib, an oral tyrosine kinase inhibitor (TKI), administered in patients with advanced non-small cell lung cancer (NSCLC), not progressing following standard 1st-line chemotherapy. Methods: Patients with advanced NSCLC, not-progressing after four cycles of platinumbased chemotherapy, were randomised to receive either gefitinib 250 mg/d or matched placebo until progression or unacceptable toxicity. The primary end-point was overall survival (OS). Secondary end-points were progression-free survival (PFS) and toxicity. The study was powered to detect a 28% increase in OS from a median of 11–14.1 months (HR = 0.78) and planned to randomise 598 patients to observe 514 deaths. Results: After inclusion of 173 patients, the trial was prematurely closed due to low accrual. Baseline characteristics for gefitinib (n = 86) and placebo (n = 87) arms were well balanced. After a median follow up of 41 months, the difference in median OS in the gefitinib and placebo arms was not statistically significant (10.9 and 9.4 months, HR 0.83 [95% confidence interval (95% CI) 0.60–1.15]; p = 0.2). The difference in median PFS significantly favoured gefitinib (4.1 and 2.9 months, HR = 0.61, [95% CI 0.45, 0.83]), p = 0.0015). Adverse events reported in more than 10% of patients were rash (47% with gefitinib versus 13% with placebo) and diarrhoea (34% with gefitinib versus13% with placebo). Conclusions: Despite its premature closure, this trial confirms previous evidence that consolidation gefitinib is safe and improves PFS. However, no difference in OS was observed in this study (NCT00091156). Keywords: Non-small cell lung cancer; Chemotherapy; Gefitinib; EGFR; EORTC.

Imatinib mesylate has dramatically improved the prognosis of chronic myeloid leukemia (CML) patients with an estimated six years overall survival of 88%. More than 50% of all CML, patients are males and 45.8% are diagnosed between 20 and 64 years of age, but no clear data about the potential gonadotoxicity and possible harmful effects on offspring of imatinib are available. Imatinib is a small-molecular analog of ATP that inhibits the tyrosine kinase activities of Bcr-Abl, PDGFR-α, PDGFR-β, c-Fms, Arg and c-kit. In rodents, c-kit and its ligand SCF play an essential role in testicular development regulating germ cells migration, proliferation and survival. In addition, PDGFR is a central mediator in the maturation of Leydig cells. Accordingaly, inhibition of these developmental signaling pathways could have adverse effects on normal sperm and testosterone production. Animal and human data suggest that prolonged exposure to imatinib could be associated with low sperm count, even if this may not affect fertility as demonstrated by the reported cases. Nonetheless, patients should be counselled about the possibility that azoospermia might eventually occur and should be encourged to bank their sperm either before or during therapy. Even if data are limited, imatinib therapy does not seem to be associated with major fetal complication when conception occurred during the treatment of the male partner. However, prolonged follow-up of the offspring and specific studies on sperm integrity and testosterone production and warranted. Keywords: Imatinib; Male Fertility; Spermatogenesis.

Malignant Pleural Mesothelioma (MPM) is nearly invariably lethal tumor of the pleura. Significant therapeutic nihilism exists among health professionals. Recent progress has reshaped the clinical landscape in the treatment of MPM. Two European guidelines have been published, one from the Task force of the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS) and the other from the European Society of Medical Oncology (ESMO). With these guidelines and recommendations as a guidepost, this review discusses the major changes and their impact on the management of MPM. Keywords: Mesothelioma; Pleura; Treatment; Guidelines.

54www.gsrd.cu.edu.eg

543. A Double-Blind, Randomised, Placebo-Controlled Phase III Intergroup Study of Gefitinib in Patients with Advanced NSCLC, non Progressing After First Line Platinum-Based Chemotherapy (EORTC 08021/ILCP 01/03) Rabab M. Gaafar, Veerle F. Surmont, Giorgio V. Scagliotti, Rob J. Van Klaveren, Demetris Papamichael, John J. Welch, Baktiar Hasan, Valter Torri andJan P. van Meerbeeck European Journal of Cancer, 47: 2331-2340 (2011) IF: 4.944

544. Fatherhood During Imatinib Emad Shash, Simona Bassi, Emilia Cocorocchio, Giovanni Maria Colpi, Saverio Cinieri and Fedro Alessandro Peccatori Acta Oncologica, 50(5):734-735 (2011) IF: 3.137

545. European Guidelines for the Management of Malignant Pleural Mesothelioma Eric van Thiel, Rabab Gaafar and Jan P. van Meerbeeck Journal of Advanced Research, 2: 281–288, (2011) IF: 3.00

Vol. 6 (2), Oct.2012

McKee and Schover have suggested that sexuality is an aspect of intimicy that is frequently compromised by cancer and its treatments. Cancer, both in terms of diagnosis and treatments, may have a dramatic impact on both intimicy and sexuality. There is a body of published research addressing sexual concerns among patients with prostatic, testicular, breast and rectal cancers. This issue seems to be less well documented in patients who have undergone haematopoeitic stem cell transplantation (HSCT). In this review, we seek to elaborate different points regarding sexuality and how it is affected in patients undergoing HSCT, with the aim of identifying optimum solutions for such patients in confronting such problems in the course of cancer treatment. Keywords: Sexuality; HSCT; Hematological malignancies.

In Egypt, although cancer is now the second leading cause of death, oncology teaching in medical schools is fragmented and is studied within the core of other topics, such as surgery and pathology. This diversity leads to a non-unified approach; and medical students graduate knowing little about the management of cancer patients. Following previous individual attempts, we decided to develop an intense summer course for medical students of Egypt and the Middle East as a step forward to enhance the knowledge of our future physicians. Keywords: Oncology; Medical Students; Cancer Education.

Lung cancer is the leading cause of cancer-related death in US and Europe. Treatment with a platinum-based chemotherapy remains the standard of care, however with modest effect on quality of life and overall survival which seldom reaches 1 year. Recently, several classes of targeted agents have emerged

showing promising results. In particular, agents targeting the epidermal growth factor receptor (EGFR) showed impressive clinical activity both in the first line and salvage settings. However, it is evident that these drugs are not effective in all patients. Putting into consideration the very high cost of these agents, there is an urgent need to provide reliable tools to identify those patients that would derive the maximum benefit from these drugs. Several predictive biomarkers were developed to identify those patients who would derive the maximal benefit of these drugs. In this review we will discuss the recent updates on the role of EGFR inhibitors in the treatment of advanced NSCLC and the role of predictive bio-markers in patient selection. Keywords: Advanced NSCLC;

Gefitinib; Erlotinib; EGFR; Biomarkers; Cetuximab.

Pancreatic neuroendocrine tumors (PNETs) are relatively rare and generally considered to follow an indolent course. However poorly differentiated or metastatic PNETs can also behave in an aggressive manner with a 5-year survival as low as 30% in non-functioning PNETs. Many therapeutic agents have been tested in the treatment of NET including Interferon alfa, streptozocin or temozolomide-based combination chemotherapy with an objective response of 10%–30%. Moreover these agents are less effective in patients with advanced carcinoid tumors and their prolonged use is often associated with added toxicity. A number of other signaling pathways have also been implicated in neuroendocrine tumors, which also express platelet-derived growth factor (PDGF), PDGF receptor (PDGFR), insulin-like growth factor-1, insulin-like growth factor receptor, basic fibroblast growth factor, transforming growth factor, epidermal growth factor receptor, and stem-cell factor receptor. Sunitinib malate (SUTENT®; Pfizer Oncology) is a small molecule kinase inhibitor with activity against a number of tyrosine kinase receptors, including VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-, PDGFR-, stem-cell factor receptor, glial cell line derived neurotrophic factor receptor and FMS-like tyrosine kinase-3. This review will present data regarding sunitinib progress in PNET, demonstrating its effectiveness and the emerging hope it may provide for such a disease with limited treatment options. Keywords: Sunitinib; Neuroendocrine; VEGFR; PDGFR; Efficacy.

3-4-05. Dept. of Pathology

55www.gsrd.cu.edu.eg

546. Sexuality in Patients Undergoing Haematopoietic Stem Cell Transplantation Sarah Jayne Liptrott, Emad Shash and Giovanni Martinelli International Journal of Hematology, 94 (6): 519-524 (2011) IF: 1.324

547. Teaching Oncology to Medical Students is a Must: the Egyptian NCI Step on the Road Rabab Gaafar, Emad Shash, Alaa El-Haddad and Salah Abdel Hady Journal of Cancer Education, 26 (3): 547-548 (2011) IF: 0.682

548. Optimizing the use of Epidermal Growth Factor Receptor Inhibitors in Advanced Non-Small-Lung Cancer (NSCLC) Emad Shash, Fedro Alessandro Peccatori and Hatem A Azim Jr Clinical Medicine Reviews in Oncology, 3 (1): 57-64 (2011)

549. Sunitinib Efficacy in Advanced Pancreatic Neuroendocrine Tumors Mohamed Abdulla and Emad Shash Clinical Medicine Reviews in Oncology, 3: 71–77 (2011)

Vol. 6 (2), Oct.2012

Background: The outcome of colorectal cancer varies depending on ethnic origin. Egyptian colorectal carcinoma is surprisingly young-age disease with high proportion of rectal and advanced stage cancers. Methods: We characterized 69 sporadic Egyptian colorectal cancers for promoter methylation at 24 tumor suppressor genes, microsatellite instability, and expression of mismatch repair, p53, and b-catenin proteins. Data were compared with 80 Western colorectal carcinoma of sporadic and familial origin from Finland. Results: Egyptian colorectal carcinomas showed significantly higher methylation of the microsatellite stable (MSS) tumors as reflected by the average number of methylated genes per case (P ¼ 0.00002) and tumor suppressor gene methylator phenotype (TSGMP), defined here as methylation of _5 genes, (P ¼ 0.0001) compared with the sporadic Western cancers. The TSGMP was associated with advanced stage in the Egyptian cancers (P¼0.0016). Four genes were differentially methylated between Egyptian and Western cases, of which the association of CDKN2B/p15 methylation with Egyptian origin was outstanding (P ¼ 4.83E-10). Egyptian carcinoma also showed significantly lower frequency of nuclear b-catenin localization than the sporadic Western cancers (P¼0.00006) but similar to that of the familial Western subset designated as familial colorectal cancer type X. Conclusions: We show novel pathway in colon carcinogenesis marked by high methylation of MSS cancers, remarkable CDKN2B/p15 methylation, and low frequency of Wnt signaling activation. Impact: Our findings highlight the possible effect of environmental exposures in carcinogenesis through DNA methylation and should have applications in prevention, molecular diagnosis, prognosis, and treatment. Keywords: Genetic and Epigenetic Signatures Colorectal Cancers.

Altered cell cycle regulatory genes expression contributes to HCV-associated liver disease. We sought to assess the role of

cyclins and cyclin dependent kinases (CDKs) in HCV-associated CH and HCC. Aberrant expression of cyclins A, E, D1, CDK2 and CDK4 was assessed by immunohistochemistry and differential PCR in HCV-associated CH and HCC with pericarcinomatous foci (PCF). S phase fraction (SPF) was determined by flow cytometry. Results were correlated with overall survival (OS) in HCC patients. In HCC, cyclins A, E, D1, CDK2 and CDK4 protein overexpression was detected in 52.8%, 52.8%, 69%, 47% and 58% compared to 36.1%, 33%, 56%, 27.8%, 55.6% for CH and 36.1%, 27%, 30.6%, 27%, 50% for PCF. Gene amplification was detected in 38.9%, 33% 66%, 33%, 44% of HCC compared to 27.8%, 25%, 44%, 27.8%, 36% in CH and 25%, 22.2%, 38.9%, 27%, 33% in PCF. A significant difference was reported between HCC, CH, NHT regarding cyclins A, E, D1, CDK2 (p=0.007, p=0.002, p=0.047, p=0.002) protein expression (ADD) and cyclin D1 amplification (p=0.009). Cyclins A, E, CDK2 expression was associated with fibrosis in CH (p=0.004, p=0.02, p=0.012). Reduced OS was (ADD) associated with cyclin D1 and cyclin A, grade, stage and metastasis (p=0.001, p=0.02, p=0.018, p=0.01, p=0.001). CONCLUSIONS: Increased cyclins A, E, D1, CDK2 and CDK4 expression is important for HCV-associated CH and HCC. Cyclin D1 and cyclin A are prognostic biomarkers associated

with reduced OS in HCC. Cyclin D1 aberration could identify high risk groups of CH patients prone to develop HCC.

The global rising incidence of hepatocellular carcinoma (HCC), which parallels the increase of hepatitis C virus (HCV) prevalence, has sparked a renewed interest in discovering additional HCC serum markers. In this study, we investigated the clinical use of serum E-cadherin, ICAM, MMP-2, VEGF, OPN and β-catenin as potential diagnostic makers for HCV/genotype 4-associated HCC. Twenty cases of healthy subjects, 11 cases with asymptomatic HCV/genotype 4 carriers (ASC), 28 chronic hepatitis (CH) cases and 32 patients with HCC were enrolled in this study. Serum levels of proteins were measured by a sandwich-enzyme-linked (ELISA) assay. The diagnostic accuracy of each candidate marker was evaluated using receiver-operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). We demonstrated that serum β-catenin levels were significantly elevated in patients with HCC compared to those with CH, ASC and healthy controls. Among the six studied markers, β-catenin was also found to be the only marker that can significantly discriminate between patients with HCC and those with CH;

56www.gsrd.cu.edu.eg

551. Distinct Genetic and Epigenetic Signatures of Colorectal Cancers According to Ethnic Origin Taina T. Nieminen, Soheir Shoman, Saad Eissa, P€aivi Peltom€aki and Wael M. Abdel-Rahman Cancer Epidemiol Biomarkers Prev American Association for cancer research, 21(1): 202–211 (2011) IF: 3.919

552. The Role of Cyclins and Cyclin Dependent Kinases in Development and Progression of Hepatitis C Virus-Genotype 4-Associated Hepatitis and Hepatocellular Carcinoma Bahnassy AA, Zekri AR, Loutfy SA, Mohamed WS, Moneim AA, Salem SE, Sheta MM, Omar A and Al-Zawahry H. Experimental and Molecular Pathology , 91: 643-652 (2011) IF: 2.986

553. Serum Levels of β-catenin as a Potential Marker for Genotype 4/Hepatitis C-Associated Hepatocellular Carcinoma Zekri AR, Bahnassy AA, Alam El-Din HM, Morsy HM, Shaarawy S, Moharram NZ and Daoud SS. Oncology Reports, 23: (2011) IF: 1.686

Vol. 6 (2), Oct.2012

therefore, β-catenin could be considered as a potential marker for early diagnosis of HCV-associated HCC in patients infected with HCV genotype 4.

Inflammatory Breast Cancer (IBC) is a rare but aggressive form of breast cancer that is diagnosed clinically has characteristic clinical and biologic features suggestive of differences between IBC and non-IBC. Egypt has about a five times higher proportion of IBC patients than the USA with distinct molecular features of IBC tumors that may reflect amore aggressive nature of the disease .Within Egypt, there have been no past comparisons between IBC and non-IBC patients with respect to survival. Therefore, as a part of this study, we decided to compare survival of IBC and non-IBC patients while taking into account, the epidemiologic, pathologic, and treatment characteristics of these two groups of patients from the National Cancer Institute of Cairo University (NCI-Cairo) in Egypt. Patients included in this study were diagnosed and treated at NCI-Cairo from 2000 to 2005. The patients included two groups, 65 IBC patients and 52 non-IBC patients. IBC diagnosis was based on the presence of erythema, edema, and peau d’orange and some of the patients in this study were included in our previous studies. We reviewed the medical records, pathology reports and radiation records, and abstracted demographic, clinical and survival information (presence of metastases, treatment variables, and past medical history that is associated with overall survival). We applied the same exact procedure for abstracting information from the medical records of IBC and non-IBC patients. Survival variables included distant metastases, chemotherapy, radiation do frequency, type of surgical procedure, hormonal therapy, history of hypertension, pulmonary disease, type II diabetes, other cancers, and presence of chronic granulomatous mastitis. Duration of disease was the difference between the date of reported onset of clinical symptoms to the date of death or last date of follow- up of the patient, if lost to follow-up. In summary, the most important finding of this study was that IBC patients had a significantly lower overall survival than non-IBC patients. Future studies should continue to follow the patients over an extended period past the 4-years included in this study. Keywords: Inflammatory breast cancer.

Background: To understand the complex and largely not well-understood apoptotic pathway and immune system evasion mechanisms in hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and HCV associated chronic hepatitis (CH), we studied the expression patterns of a number of pro-apoptotic and anti-apoptotic genes (Fas, FasL, Bcl-2, Bcl-xL and Bak) in HepG2 cell line harboring HCV- genotype-4 replication. For confirmation, we also assessed the expression levels of the same group of genes in clinical samples obtained from 35 HCC and 34 CH patients. Methods: Viral replication was assessed in the tissue culture medium by RT-PCR, quantitative Real-Time PCR (qRT-PCR); detection of HCV core protein by western blot and inhibition of HCV replication with siRNA. The expression level of Fas, FasL, Bcl-2, Bcl-xL and Bak was assessed by immunohistochemistry and RT-PCR whereas caspases 3, 8 and 9 were assessed by colorimetric assay kits up to 135 days post infection. Results: There was a consistent increase in apoptotic activity for the first 4 weeks post-CV infection followed by a consistent decrease up to the end of the experiment. The concordance between the changes in the expression levels of Fas, FasL, Bcl-2, Bcl-xL and Bak in vitro and in situ was statistically significant (p < 0.05). Fas was highly expressed at early stages of infection in cell lines and in normal control liver tissues followed by a dramatic reduction post-HCV infection and an increase in the expression level of FasL post HCV infection. The effect of HCV infection on other apoptotic proteins started very early post-infection, suggesting that hepatitis C modulating apoptosis by modulating intracellular pro-apoptotic signals. Conclusions: Chronic HCV infection differently modulates the apoptotic machinery during the course of infection, where the virus induces apoptosis early in the course of infection, and as the disease progresses apoptosis is modulated. This study could open a new opportunity for understanding the various signaling of apoptosis and in the developing a targeted therapy to inhibit viral persistence and

HCC development. 3-4-06. Dept. of Surgical Oncology

Background Irradiation of the pelvis in the treatment of cancers will result in ovarian failure unless the ovaries are shielded

57www.gsrd.cu.edu.eg

554. Survival of Inflammatory Breast Cancer Patients Compared to Non-inflammatory Breast Cancer Patients in Egypt Brooke Spencer, Mousumi

Banerjee, Sherif Omar, Hussein Khaled, Nayera Anwar,

Mohamed S. Zaghloul, Saad Eissa, Celina G. Kleer, Subhojit

Dey, Sofia D. Merajver and Amr S. Soliman Breast journal,

17 (5): 545–547 (2011) IF: 1.425

555. Characterization of Chronic HCV Infection-Induced Apoptosis Zekri AR, Bahnassy AA, Hafez MM, Hassan ZK, Kamel M, Loutfy SA, Sherif GM, El-Zayadi AR and Daoud SS. Comparative Hepatology, 10 (4): (2011) IF: 2.500

556. Needle oophoropexy: a new simple technique for ovarian transposition prior to pelvic irradiation Waheed Gareer, Zeiad Gad and Haytham Gareer. Surg Endosc., 25 (7): 2241-2246 (2011) IF: 3.436

Vol. 6 (2), Oct.2012

adequately. To protect the ovaries, an oophoropexy may be performed. Our aim was to evaluate the feasibility, morbidity, and efficacy of laparoscopic ovarian transposition using a simple percutaneous needle technique. Methods Fifteen patients (ten with rectal cancer and five with Hodgkin’s disease) underwent the new laparoscopic oophoropexy technique. Laparoscopic releasing of the ovary was performed by cutting the utero-ovarian ligament followed by placing the ovaries on the anterior abdominal wall. A percutaneous straight needle was introduced through a 2-mm skin incision at the site of fixation. Repositioning of the ovaries was done on an outpatient basis without the need for readmission to the operating theatre. Results The technique was effective, reliable, and simple with no morbidities. Repositioning was performed simply in the outpatient clinic. At follow-up, 11 patients had evidence of ovarian function. Conclusion Percutaneous needle transposition of the ovaries is a simple, effective, reliable, and easy-to-perform technique. It has short learning curve and can be done by less experienced laparoscopic surgeons. Keywords: Hodgkin’s disease; Laparoscopy; Oophoropexy; Rectal cancer.

3-4-07. Dept. of Virology and Immunology

Background: Hepatitis C virus (HCV) infection is a well-documented etiological factor for hepatocellular carcinoma (HCC). As HCV shows remarkable genetic diversity, an interesting and important issue is whether such a high viral genetic diversity plays a role in the incidence of HCC. Prior data on this subject are conflicting. Objectives: Potential association between HCV genetic mutations or strain variability and HCC incidence has been examined through a comparative genetic analysis merely focused on a single HCV subtype (genotype 4a) in a single country (Egypt). Study Design: The study focused on three HCV sequence datasets with explicit sampling dates and disease patterns. An overlapping HCV Core/E1 domain from three datasets was used as the target for comparative analysis through genetic and phylogenetic approaches. Results: Based on partial Core/E1 domain (387 bp), genetic and phylogenetic analysis did not identify any HCC-specific viral mutations and strains, respectively. Conclusions: The Core/E1 domain of HCV genotype 4a in Egypt does not contain HCC-specific mutations or strains. Additionally, sequence errors resulting from the polymerase chain reaction, together with a strong evolutionary

pressure on HCV in patients with end-stage liver disease, have significant potential to bias data generation and interpretation.

58www.gsrd.cu.edu.eg

557. The Core/E1 Domain of Hepatitis C Virus Genotype 4a in Egypt Does not Contain Viral Mutations or Strains Specific for Hepatocellular Carcinoma Zhang X, Ryu SH, Xu Y, Elbaz T, Zekri AR, Abdelaziz AO, Abdel-Hamid M, Thiers V, Elena SF, Fan X and Di Bisceglie AM. Journal of Clinical Virology, 52: 333-338 (2011) IF: 4.023

Vol. 6 (2), Oct.2012

2012 , Oct The National Cancer Institute

Dept. of Medical Oncology

179. Optimisation of Breast Cancer Management in Low-Resource and Middle-Resource Countries: Executive Summary of the Breast Health Global Initiative Consensus

Anderson, B.O., Cazap, E., El Saghir, N.S., Yip, C.-H., Khaled, H.M., Otero, I.V., Adebamowo, C.A., Badwe, R.A. and Harford, J.B.

The Lancet Oncology, 12 (4): 387-398 (2011) IF: 17.764

The purpose of the Breast Health Global Initiative (BHGI) 2010 summit was to provide a consensus analysis of breast cancer control issues and implementation strategies for low-income and middle-income countries (LMCs), where advanced stages at presentation and poor diagnostic and treatment capacities contribute to lower breast cancer survival rates than in high-income countries. Health system and patient-related barriers were identified that create common clinical scenarios in which women do not present for diagnosis until their cancer has progressed to locally advanced or metastatic stages. As countries progress to higher economic status, the rate of late presentation is expected to decrease, and diagnostic and treatment resources are expected to improve. Health-care systems in LMCs share many challenges including national or regional data collection, programme infrastructure and capacity (including appropriate equipment and drug acquisitions, and professional training and accreditation), the need for qualitative and quantitative research to support decision making, and strategies to improve patient access and compliance as well as public, health-care professional, and policy-maker awareness that breast cancer is a cost-effective, treatable disease. The biggest challenges identified for low-income countries were little community awareness that breast cancer is treatable, inadequate advanced pathology services for diagnosis and staging, and fragmented treatment options, especially for the administration of radiotherapy and the full range of systemic treatments. The biggest challenges identified for middle-resource countries were the establishment and maintenance of data registries, the coordination of multidisciplinary centres of excellence with broad outreach programmes to provide community access to cancer diagnosis and treatment, and the resource-appropriate

prioritisation of breast cancer control programmes within the framework of existing, functional health-care systems.

180. Associations Differ by Sex for Catechol-O-Methyltransferase Genotypes and Bladder Cancer Risk in South Egypt (Article in press)

Wolpert, B.J., Amr, S., Saleh, D.A., Ezzat, S., Gouda, I., Loay, I., Hifnawy, T., Abdel-Hamid, M., Mikhail, N.N., Zhan, M., Zheng, Y.-L., Squibb, K., Abdel-Aziz, M.A., Zaghloul, M.S., Khaled, H. and Loffredo, C.A.

Urologic Oncology: Seminars and Original Investigations, (2011) IF: 3.172

Objectives: To examine associations between urinary bladder cancer risk and polymorphisms of the gene encoding the catechol estrogen-metabolizing enzyme, catechol-O-methyltransferase (COMT), among Egyptian women and men. Materials and methods: We used questionnaire and genotype data from a case-control study in Egypt. This analysis focused on South Egypt cases with confirmed urothelial (UC) or squamous cell (SCC) carcinoma of the bladder, and controls frequency-matched on sex, 5-year age-group, and residence governorate. Real-time PCR on blood specimen DNA was used to determine COMT genotypes encoding for Val/Val, Val/Met, and Met/Met, the enzyme forms associated with high, intermediate, or low activity, respectively. Results: The study sample, which included 255 women and 666 men, consisted of 394 cases with histologically confirmed UC (225) or SCC (n = 169), and 527 controls. The odds of having either type of bladder cancer was lower among men with genotypes encoding Val/Met or Met/Met than among those with the genotype encoding Val/Val, even after adjustment for other factors, such as smoking and schistosomiasis history [adjusted odds ratio (AOR): 0.64; 95% confidence interval (CI): 0.43, 0.96]; however, the association was statistically significant for SCC (AOR 0.57; 95% CI: 0.34, 0.96) but marginal for UC (AOR: 0.64; 95% CI: 0.39, 1.02). No significant associations were detected between bladder cancer risk and COMT genotypes among postmenopausal women. Conclusions: These findings suggest that even after controlling for established risk factors, the involvement of COMT genotypes in bladder cancer risk differs among men compared with women in South Egypt.

181. Gem-(R)CHOP Versus (R)CHOP: A Randomized Phase II Study of Gemcitabine Combined with (R) CHOP in Untreated Aggressive Non-Hodgkin's Lymphoma - EORTC Lymphoma

59www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

Group Protocol 20021 (EudraCT Number 2004-004635-54)

Aurer, I., Eghbali, H., Raemaekers, J., Khaled, H.M., Fortpied, C., Baila, L. and Van Der Maazen, R.W.

European Journal of Haematology, 86 (2): 111-116 (2011) IF: 2.785

Background: Despite recent improvements, many patients with aggressive non-Hodgkin's lymphoma (NHL) ultimately succumb to their disease. Therefore, improvements in front-line chemotherapy of aggressive NHL are needed. Gemcitabine is active in lymphoma. Methods: We performed a randomized phase II trial of the addition of gemcitabine to standard CHOP chemotherapy with or without rituximab [(R)CHOP]. The trial was also designed to determine the maximal tolerated dose (MTD) of gemcitabine in this combination. Patients with previously untreated aggressive NHL were randomized to receive either eight cycles of (R)CHOP given every 3 wk or (R)CHOP combined with gemcitabine [Gem-(R)CHOP]. Results: Twenty-five patients were enrolled in the trial before early closure. Twelve were randomized to Gem-(R)CHOP and 13 to (R)CHOP. MTD of gemcitabine was 800 mg/m 2 given on days 1 and 8; dose-limiting toxicity was hematologic. Five patients (42%) treated with Gem-(R)CHOP achieved complete response in comparison with 10 (77%) treated with (R)CHOP. Median time to treatment failure was 1.5 yr for Gem-(R)CHOP and 3.1 yr for (R)CHOP. Three patients receiving Gem-(R)CHOP had serious pulmonary toxicity, when compared to none receiving (R)CHOP. One patient died of pneumonitis. Conclusions: In this group of patients, addition of gemcitabine did not seem to improve outcomes. Gem-(R)CHOP in previously untreated patients with aggressive NHL occasionally results in severe, potentially fatal, pulmonary toxicity. © 2010 John Wiley & Sons A/S.

182. Breast Cancer Management in Middle-Resource Countries (Mrcs): Consensus Statement from the Breast Health Global Initiative

Yip, C.-H., Cazap, E., Anderson, B.O., Bright, K.L., Caleffi, M., Cardoso, F., Elzawawy, A.M., Harford, J.B., Krygier, G.D., Masood, S., Murillo, R., Muse, I.M., Otero, I.V., Passman, L.J., Santini, L.A., Da Silva, R.C.F., Thomas, D.B., Torres, S., Zheng, Y. and Khaled, H.M.

Breast, 20 (2): 512-519 (2011) IF: 2.089

In middle resource countries (MRCs), cancer control programs are becoming a priority as the pattern of disease shifts from infectious diseases to non-communicable diseases such as breast cancer, the most common cancer among women in MRCs. The Middle Resource Scenarios Working Group of the BHGI 2010 Global Summit met to identify common issues and obstacles to breast cancer detection, diagnosis and treatment in MRCs. They concluded that breast cancer early detection programs continue to be important, should include clinical breast examination (CBE) with or without mammography, and should be coupled with active awareness programs. Mammographic screening is usually opportunistic and early detection programs are often hampered by logistical and financial problems, as well as socio-cultural barriers, despite improved public educational efforts. Although multidisciplinary services for treatment are available, geographical and economic limitations to these services can lead to an inequity in health care access. Without adequate health insurance coverage, limited personal finances can be a significant barrier to care for many patients. Despite the improved availability of services (surgery, pathology, radiology and radiotherapy), quality assurance programs remain a challenge. Better access to anticancer drugs is needed to improve outcomes, as are rehabilitation programs for survivors. Focused and sustained government health care financing in MRCs is needed to improve early detection and treatment of breast cancer.

183. Efficiency of Diagnostic Biomarkers Among Colonic Schistosomiasisegyptian Patients

Hamed, M.A.A., Ahmed, S.A.A. and Khaled, H.M.

Memorias do InstitutoOswaldo Cruz, 106 (3): 322-329 (2011) IF: 2.058

The schistosomal parasite plays a critical role in the development of malignant lesions in different organs. The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for disease detection. The objective of this paper is to evaluate certain biochemical parameters as diagnostic tools to efficiently differentiate between colonic carcinoma and colonic carcinoma associated with schistosomal infection among Egyptian patients. The parameters under investigation are interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α), carcinoembryonic antigen (CEA) levels, tissue telomerase, pyruvate kinase (PK), glucose-6-phosphate

60www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

dehydrogenase (G-6-PD) and lactate dehydrogenase (LDH) enzyme activities. The results revealed a significant elevation in the level of the tumour markers IL-2, TNF-α and CEA as well as the activities of LDH, telomerase and G-6-PD among non-bilharzial and bilharzial colonic cancer groups, with a more potent effect in bilharzial infection-associated colonic cancer. A significant inhibition in PK activity was recorded in the same manner as compared to normal tissues. The efficacy of this biomarker was also evaluated through detecting sensitivity, specificity, negative and positive predictive values. In conclusion, schistosomal colonic carcinoma patients displayed more drastic changes in all parameters under investigation. The combination of the selected parameters succeeded in serving as biomarkers to differentiate between the two malignant types.

184. Diffuse Large B-Cell and Peripheral T-Cell Non-Hodgkin's Lymphoma in the Frail Elderly. A Phase II EORTC Trial with A Progressive and Cautious Treatment Emphasizing Geriatric Assessment

Soubeyran, P., Khaled, H., MacKenzie, M., Debois, M., Fortpied, C., De Bock, R., Ceccaldi, J., De Jong, D., Eghbali, H., Rainfray, M., Monnereau, A., Zulian, G. and Teodorovic, I.

Journal of Geriatric Oncology, 2 (1): 36-44 (2011)

Objectives: Many frail elderly patients with diffuse large B-cell lymphoma (DLBCL) cannot tolerate standard chemotherapy treatment. The objective of this phase II trial was to assess the efficacy of a cautious COP-based (cyclophosphamide, vincristine, prednisone) regimen with comprehensive geriatric assessment (CGA). Trial registration number: NCT00039351. Materials and methods: DLBCL patients aged ≥70years with poor physiological functioning received cyclophosphamide (750mg/m 2 IV at d1), vincristine (1.4mg/m 2 IV at d1, maximum of 2mg) and prednisone (40mg/m 2 d1 to d5) for six cycles. Comprehensive Geriatric Assessment (CGA) was performed for all patients before and after treatment. Results: Thirty-two patients were included, of whom 27 were evaluable for efficacy. Low response rates were observed with only 18.5% complete response and 25.9% partial response leading to the early termination of the trial. Despite strict dose reduction rules, high toxicity rates were observed with four severe toxicities and eight early deaths. CGA data showed that over 90% of patients were depressed, over 80% dependent for instrumental activities of daily living (IADL)

and almost half of our patients had severe comorbidities showing that we clearly selected a population of "frail" elderly. Conclusion: This adapted COP regimen for vulnerable patients produced an 18.5% complete response rate. Future research will include the addition of rituximab to determine if it can improve treatment efficacy. The geriatric assessment should be part of routine management of frail patients with aggressive lymphomas as it allows us to identify specific issues of vulnerability in this population on which intervention should be focused.

61www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

185. Levels of Certain Tumor Markers as Differential Factors between Bilharzial and Non-Biharzial Bladder Cancer Among Egyptian Patients

Metwally, N.S., Ali, S.A., Mohamed, A.M., Khaled, H.M. and Ahmed, S.A.

Cancer Cell International, 11 (7): (2011)

Background/Objective: Bladder cancer is the commonest type of malignant tumors as a result of schistosomaisis which is a major healthy problem in many subtropical developing countries. The aim of this study is to comparatively elucidate the underlying biochemical tumor markers in schistosomal bladder cancer versus non-schistosomal bladder cancer when compared to normal healthy ones. Methods: This work was performed on tissue specimens from total 25 patients and serum samples from total 30 patients versus ten healthy individuals served as control. The investigated parameters in serum are: xanthine oxidase (XO), fructosamine, lactate dehydrogense (LDH), aspartate amino - transferase (AST), alanine aminotransferase (ALT), total proteins, essential and non- essential amino acids profile, hydroxyproline, total immunoglobulin E (IgE) and tumor necrosis factor alpha (TNF-α). In addition, the current investigation also extended to study some markers in tumor bladder tissues including, pyruvate kinase enzyme (PK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Results: Results showed that biharzial bladder cancer patients recored more significant elevation in serum XO, fructosamine, LDH, AST, ALT, hydroxyproline, IgE and TNF-α than in bladder cancer patients when compared to control ones. While, in tissues there were significant increase in PK, LDH, AST & ALT activities of schistosomal bladder cancer than in bladder cancer as compared to control healthy patients. Conclusions: It could be concluded that, bilharzial and non-bilharzial bladder cancer showed distinct biochemical profile of tumor development and progression which can be taken

into consideration in diagnosis of bladder cancer. Dept. of Radiation Oncology

186. Joint Genitourinary Cancer Symposium Between Egyptian and American Centers

Mohamed Saad Zaghloul

Expert Rev Anticanc, 11 (5): 697-699 (2011) IF: 2.976

Mansoura–Cleveland Clinic–UCSF Joint Genitourinary Symposium The Egyptian Cancer Society, Mansoura, Egypt, 6 January 2011 A joint symposium between Mansoura and Cleveland Universities, and the University of California, San Francisco (CA, USA) was held by the Egyptian Cancer Society in Mansoura, Egypt. The Symposium extensively discussed two topics: prostate and bladder cancer. The experiences of American and Egyptian scientists were shared in a trial to increase understanding, improve management, increase treatment outcome and decrease morbidity. Comparisons between treatment policies, management techniques and survival end results in Egypt and the USA, as well as internationally, were performed in both bladder and prostate cancer in order to determine the best policies for their management. Joint genitourinary cancer symposium between Egyptian and American centers Expert Rev. Anticancer Ther. 11(5), 697–699 (2011) multidisciplinary care of locally advanced prostate cancer was discussed by Mack Roach (University of California, San Francisco, CA, USA). Although there was no randomized trial comparing radical prostatectomy to radiotherapy, retrospective studies comparing the two modalities favored external-beam radiotherapy (EBRT) and hormonal treatment in 284 patients, especially when normalized for different covariants [2,3]. The addition of brachytherapy boost could also improve results. Controversy regarding the volume of EBRT and the required techniques were extensively discussed. Roach emphasized the harmful effect of high-dose radiation to the penile bulb on the patient’s future potency. He stressed the importance of different forms of image-guided radiotherapy (IGRT) as verification for intensitymodulated radiotherapy. Daily IGRT (either through portal imaging or cone-beam computed tomography) corrects for organ movements and other setup errors, and enables an increase of the dose to the target volume with lower acceptable dose levels achieved in organs at risk. May Abdel-Wahab (Cleveland Clinic, OH, USA) discussed factors affecting the development of second malignancy after prostate cancer treatment (second primary cancers [SPCs]). Radiation dose, radiotherapy technique, dose rate, fractionation and type of radiation are among the factors increasing SPCs. A Surveillance, Epidemiology and End Results (SEER)-dependent study proved Prostate and bladder cancers are the most common genitourinary cancer types found in males. They are among the five most common malignancies worldwide. These tumors hold special importance in both the USA and Egypt. Prostate cancer is the second most common cancer among males in USA after lung cancer, while bladder cancer is still the most common cancer type among males in Egypt. The aim of this symposium was to

62www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

highlight the state of the art and the standard of care, as well as exchange ideas and experiences for the best management of prostate and bladder cancer.

187. Influence of Field Size, Depth, Nominal Dose Rate and Stem Lenghth on Ion Recombination Correction Factor in Therapeutic Photon Beam

A. I. Abd El-Hafez, Hany A. Shousha, M. S. Zaghloul and M. A. Abou Zeid.

Journal of American Science, (2011)

The use of ionization chamber in linear accelerator radiotherapy photon dosimetry requires various corrections to the measured charges, one of these being the ion recombination correction factor (ks). As stated by the IAEA (2000) TRS-398 dosimetry protocol, ks was characterized for the available thimble ionization chamber PTW 30006 using two pulsed megavoltage photon beams 6 and 10 MV. The dependence of the ks values against the changing of field size, water depth, nominal dose rate and stem length was studied. For photon energy 10 MV, ks shows an increase with the field size and for photon energy 6 MV, ks values decrease from field size 4x4 cm2 to 10x10 cm2 and increase at field sizes larger than 10x10 cm2. Also, ks values are inversely proportional with the water depth and directly proportional with the nominal dose rate and stem length, for both photon energies. It is also recommended to determine the absorbed dose at lower (p.r.f) pulse repetition frequency or nominal dose rate. If the dose is determined at the highest (p.r.f), a correction must be introduced in the assessment of the dose related to the ion recombination correction factor ks difference at different p.r.fs. These measurements help to correct ks values at different dosimetry conditions and minimize the errors in the assessment of the radiotherapeutic dose calculations.

Keywords: Ion recombination correction factor; Ionization chamber; Megavoltage x-ray; Pulsed photon beams and linear accelerator.

Dept. of Surgical Oncology

188. Primary Repair of Rectovaginal Fistulas Complicating Pelvic Surgery by Gracilis Myocutaneous Flap

Omaya A.H. Nassar

Gynecol Oncol, (2011) IF: 3.76

Objectives: Complex rectovaginal fistulas repair are extremely challenging. Various surgical options have been suggested; nevertheless, none had been universally accepted as the procedure of choice. This study discussed a novel surgical technique using gracilis myocutaneous flap interposition. Methods: Ten patients had fistulas as a complication post treatment of pelvic malignant tumors and one patient had fistula after resection of rectal endometriosis. Primary treatment was pelvic resection; nevertheless, 6 cases had adjuvant chemo-irradiation, 2 cases had post operative irradiation and 2 patients had adjuvant chemotherapy. Fistulas mean diameter was 2±0.24 cm (1-3) and 8 patients (72.7%) had their fistulas in the middle vaginal third. All cases had synchronous diverting stomas and wide debridement of fistulas. According to vaginal defect diameter 5 patients were repaired by single gracilis myocutaneous flaps, 2 cases by simple gracilis muscle and 4 cases by double gracilis myocutaneous flaps. Results: Patients had a mean follow-up time of 34.8±5.03 months (12-67) and all patients had definitive healing of their fistulas (100%). Median time to stoma closure was 2 months (1-5). Four women (36.4%) had at least one early postoperative complications including temporary leak (n=3), vaginal sepsis (n=1), partial skin paddle necrosis (n=1) and donor limb deep venous thrombosis (n=1). Late morbidities were seen in 3 cases (27.3%) including vaginal stricture, anorectal anastomotic stricture and anastomotic tumor recurrence. Conclusion: Successful repair requires adequate debridement of necrotic devascularized tissues, tissue transposition to the rectovaginal septum and reconstruction of vaginal wall. Gracilis myocutaneous flaps are ideal for this issue.

Keywords: Rectovaginal fistula; Complicated fistula repair; Gracilis myocutaneous flap; Primary repair of rectovaginal fistula.

189. Modified Pseudocontinent Perineal Colostomy: A Special Technique

Omaya A. H. Nassar

Diseases of the Colon & Rectum, 14: 1-12 (2011) IF: 2.819

Background: Innovative techniques created to restore

63www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

gastrointestinal perineal continuity after abdominoperineal resection in patients with anorectal cancer include pseudocontinent perineal colostomy, in which the colon is pulled to the perineum and wrapped with a sleeve of stretched colon segment to act as a new sphincter. Objective: We investigated perineal reconstruction with a modified pseudocontinent perineal colostomy technique. Design: Prospective cohort study. Settings: Tertiary care university hospital in Egypt. Patients: Patients with T2 or T3 anorectal cancer invading the sphincter who underwent Miles abdominoperineal resection and immediate total pelvic reconstruction between 2003 and 2007. Intervention: Reconstruction consisted of a vertical rectus abdominis myocutaneous flap with modified perineal colostomy pulled through the flap to add the high-pressure zone of the flap to that of the colostomy and to create a persistent new anorectal angle. Main Outcome Measures: Early and late complications were recorded. Functional results were evaluated at regular intervals by questionnaire, physical examination, and balloon manometry. Continence was graded according to Kirwan. Satisfaction with continence was assessed by questionnaire. Results: A total of 14 patients (3 women) were included. Tumors were adenocarcinoma (n 11), squamous cell carcinoma (n 2), and melanoma (n 1). Complete (R0) resection was achieved in all patients without perioperative deaths, major postoperative morbidity, or conversion to permanent iliac colostomy. Early postoperative complications (perineal wound infection, flap dehiscence, and partial perineal stoma necrosis) occurred in the first 4 patients. Late complications occurred in 7 patients, with mucosal prolapse in 3, stomal stricture in 4, and tumor recurrence in 1. Fecal continence progressed consistently with time, and by the end of the first year 8 patients (57%) had complete continence (grade A), 5 (36%) were continent with minor soiling (grade C), and 1 (7%) still had major soiling (grade D). After 6 months, 9 patients (64%) were satisfied with continence; after 1 year, 13 patients (93%) were satisfied. Regular enemas were necessary during the first year to improve soiling, and 8 patients (57%) were not in need after that. At 37 months median follow-up, 8 of 9 evaluable patients (89%) were satisfied with continence (grade A) without regular enemas. Limitations: This was a preliminary observational study with no control group. Conclusions: Total orthotopic pelvic reconstruction with autologous tissue transposition to rebuild the principle anorectal continence elements is feasible with minor complications, and is oncologically safe. This new technique offered high continence satisfaction independent of regular enemas and electrical stimulation.

Keywords: Anorectal cancer; Abdominoperineal resection; Total perineal reconstruction; Vertical rectus abdominis

myocutaneous flap; Continent perineal colostomy.

190. Experience with Ureteroenteric Strictures After Radical Cystectomy and Diversion: Open Surgical Revision

Omaya A. H. Nassar and Mohamed E. S. Alsafa

Reconstructive Urology, (2011) IF: 2.334

Objectives: To evaluate the long term results of the treatment of benign ureteroenteric strictures as a serious complication after urinary diversion and to highlight on the precautions for the active intervention. The outcomes of endoureteral and open surgical revisions in our patients are described. Methods: Of 658 patients who had undergone radical cystectomy for bladder cancer from 1999 to 2009, 58 had developed benign stricture. The diversions used in this subgroup were orthotopic neobladder (53.4%), ileal conduit (27.6%), and ureterocolic (19%). The median interval to the diagnosis was 6 months, and 63.8% were on the left side. Endouretral interventions (dilation and stent or endoureterotomy) were the initial treatment in 37 patients. Thirty-two patients including patients who failed endoluminal interventions and patients with bilateral strictures underwent open surgery. Success was defined as radiologic improvement and the absence of flank pain, infection, or the need for a ureteral stent or nephrostomy tube. Results: Endoscopic intervention was successful in 19 (51.3%) of 37 patients, principally those with strictures 1 cm with no difference between side, diversion type, or implantation technique. A total of 32 patients underwent open stricture resection and repair by direct implantation or tissue interposition to bridge long defects (6 Boari flaps and 7 ileal segments). At a median follow-up of 47 months, 25 patients had long-term success (78%) and 36 (83.7%) of 43 repaired units had improvement. Improvement was superior for right-sided strictures compared with left-sided strictures (100% vs 75.8%) and for neobladder compared with other diversions (90% vs 69%). Both anastomotic and ureteral strictures were repaired with equivalent results (87.5% vs 82.8%). Conclusions: Although endouretral procedures are viable treatment alternatives, open surgical revision is the preferred long-term definitive treatment. Bilateral and long left-sided strictures 1 cm long are indications for early open surgery.

191. Salvage Mastectomy for Ipsilateral Breast

64www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

Tumor Recurrence After Breast Conserving Therapy

Abd-El Hamid H. Ezzat, Ashraf H. Ibrahim and Reda Tabashy

Breast, (2011) IF: 2.089

The role of breast conserving surgery (BCS) with radiation therapy (RT) in the treatment of early breast cancer has been firmly established over the past 25 years. Large randomized controlled trials have confirmed that long term survival is not impacted by the choice between initial mastectomy and BCS with RT [1-4]. Specifically, the National Surgical Adjuvant Breast and Bowel project (NSABP) B-06 trial demonstrated that the 20 year survival was equivalent for mastectomy and BCS with RT [2]. Unfortunately, conservative surgery is still associated with higher rates of local recurrence in the form of IBTR compared with mastectomy [2-4]. Veronesi and his colleagues report a cumulative 20 year incidence of local failure after BCS of 8.8 per cent compared with a rate of 2.3 per cent after mastectomy [3]. Because IBTR is not uncommon after BCS, physicians should be cognizant of risk factors for recurrence. Studies have reported that in addition to administration of radiation therapy, younger age at lumpectomy [5-8], positive surgical margin [9-11] and clinical tumor size [12, 13] are risk factors for IBTR. Recent data from the NSABP found that older age, black race, higher body mass index, larger tumors and occurrence of IBTR were all associated with higher overall mortality [13]. Outcomes after IBTR show a trend towards worse prognosis and higher rates of distant metastasis compared with recurrence- free patients [1, 2, 12-16].The implications of an IBTR on distant metastasis remain a source of debate. In the original article outlining the significance of IBTR using data form NSABP B-06, Fisher and his colleagues reported that recurrence after lumpectomy increases the risk of subsequent distant metastasis by 3.41 times [2]. However, it been argued that IBTR is not the cause of metastasis, but is instead a marker of increased risk regardless of treatment method [2, 14, 17]. When BCS was initially proposed, the surgical community feared the possibility of IBTR. The establishment of BCS with RT as a standard alternative to mastectomy for the treatment of most early stage breast caner makes IBTR an important focus for research. Presently, mastectomy is the standard of care for patients with IBTR. Despite this, there is a paucity of literature regarding outcomes after mastectomy for IBTR. Therefore, we chose to evaluate our experience and outcomes in this specific population.

Keywords: Breast conserving therapy (BCT); Ipsilateral breast tumor recurrence (IBTR); Post mastectomy recurrence (PMR).

192. Evaluation of Nephron Sparing Surgery for Renal Tumors: A Single Institution Experience

Hytham Abd-elkareem Ahmed, Abdelhamid Hussein Ezzat and Ismael Mourad

The Chinese-German journal of clinical oncology, (2011)

Objective: The aim of the study was to report the experience of National Cancer Institute (NCI), Cairo University, Egypt, in managing various benign and malignant renal tumors with nephron sparing surgery (NSS), and to assess its safety and feasibility. Methods: Reviewing the literature for NSS, and records of patients who underwent NSS in the period from January 2000 to December 2009 at National Cancer Institute, Cairo University regarding the patient and tumor related characteristics, the indication for NSS, operative technique, postoperative complications, full histopathological data, and follow up results. Results: The total number of patients was 17. Mean age at surgery was 30.7 years (range 1.5–65 years). Five patients had bilateral tumors during surgery. The mean tumor size was 4.5 cm (range 1–9 cm). All patients had normal preoperative kidney functions. Seven patients had an absolute indication for NSS, 6 patients had a relative indication, and 4 patients had an elective indication. All the 5 patients with bilateral tumors underwent bilateral simultaneous surgery. Cold ischemia was used in 8 patients, 1 patient was exposed to warm ischemia, manual compression was used in 2 patients, and no vascular control was applied in 6 patients. Complications were encountered in 2 patients, one of them had urinary leakage which needed reoperation, and the other had subcutaneous hematoma which was treated conservatively. Histopathological analysis revealed Wilm’s tumor (8 patients), angiomyolipoma (4 patients), renal cell carcinoma (4 patients), and hydatid cyst (1 patient). All patients had negative surgical margin. For patients with Wilm’s tumor, the mean follow up was 21.4 months (range 0–94 months), 2 patients had local recurrence, and 1 patient had distant metastasis. For patients with RCC, the mean follow up was 15.3 months (5–33 months), no patients had local recurrence or distant metastasis. All patients had normal kidney functions during postoperative and follow up periods. Conclusion: NSS is a feasible safe procedure that

65www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

can be done with acceptable complications rate and it provides a good solution for patients with bilateral tumors, early localized renal cell carcinoma, and benign tumors.

Keywords: Nephron sparing surgery (NSS); Renal tumors; Evaluation.

193. Genotypic Characterization of Helicobacter Pylori Isolates Among Egyptian Patients with Upper Gastrointestinal Diseases

Abdel Hamid H. Ezzat, Mona H. Ali, Eman A. El-Seidi, Iman E.Wali, Nagwa A.Sedky and Sherif M. M. Naguib

The Chinese-German Journal of Clinical Oncology, (2011)

Objective: Over 50% of the world populations are infected with Helicobacter pylori (H. pylori). Most subjects are asymptomatic; however, in 1994, H. pylori has been categorized as group I carcinogen. The aim of the study was to investigate the relationship between H. pylori infection and gastric cancer. Methods: Thirty gastric cancer patients (GCs) and 30 gastritis patients were enrolled in the study. H. pylori were cultured on non-selective and selective medias, infection densitywas assessed by quantitative culture. Antibiotic sensitivity testing was performed. PCR was done for the H. pylori 16S rRNAgene in addition to cagA, vacA and iceA genes. Results: H. pylori could be cultured from 100% of specimens obtained from all patients. The density of H. pylori was higher in cancer cases than in gastritis patients. The 16S rRNA was detected in all GC patients (100%) while it was only detected in 70% of gastritis patients. The cagA gene was found in 53.3% vs 13.3% of GC and gastritis patients, respectively. The vacA gene was present in all GC patients (by at least one of its alleles) while it was only found in 33.3% of gastritis patients. The vacA s1m1 combination was the most predominant genotype in GC patients, while m2 was the commonest allele in gastritis patients (10%). The iceA gene was found in 86.7% vs 40% of GC and gastritis patients, respectively. Simultaneous presence of multiple H. pylori strains was proved, both phenotypically and genotypically. Conclusion: The development of GC is linked to infection with H. pylori harboring certain virulence genes. Higher infection density of H. pylori was found in GC patients. Co-existence of more than one strain of H. pylori in the same patient occurs inboth malignant and benign lesions.

Dept. of Tumor Biology

194. Interaction of Celecoxib with Different Anti-Cancer Drugs is Antagonistic in Breast but Not in Other Cancer Cells

Raafat A. El-Awady, Ekram M. Saleh, Marwa Ezz and Abeer M. Elsayed

Toxicology and Applied Pharmacology, (255): 271-286 (2011) IF: 3.993

Celecoxib, an inhibitor of cyclooxygenase-2, is being investigated for enhancement of chemotherapy effica in cancer clinical trials. This study investigates the ability of cyclooxygenase-2 inhibitors to sensitize cells from different origins to several chemotherapeutic agents. The effect of the drug's mechanism of action and sequence of administration are also investigated. The sensitivity, cell cycle, apoptosis and DNA damage of five different cancer cell lines (HeLa, HCT116, HepG2, MCF7 and U251) to 5-FU, cisplatin, doxorubicin and etoposide±celecoxib following different incubation schedules were analyzed. Wefound antagonismbetween celecoxib and the four drugs in the breast cancer cellsMCF7following all incubation schedules and between celecoxib and doxorubicin in all cell lines except for two combinations in HCT116 cells.Celecoxib with the other three drugs in the remaining four cell lines resulted in variable interactions. Mechanistic investigations revealed that celecoxib exerts different molecular effects in different cells. In some lines, it abrogates the drug-induced G2/M arrest enhancing pre-mature entry into mitosiswith damaged DNA thus increasing apoptosis and resulting in synergism. In other cells, it enhances drug-induced G2/M arrest allowing time to repair drug-induced DNA damage before entry into mitosis and decreasing cell death resulting in antagonism. In some synergistic combinations, celecoxib-induced abrogation of G2/M arrest was not associated with apoptosis but permanent arrest in G1 phase. These results, if confirmed in-vivo, indicate that celecoxib is not a suitable chemosensitizer for breast cancer or with doxorubicin for other cancers.Moreover, combination of celecoxib with other drugs should be tailored to the tumor type, drug and administration schedule.

Keywords: Celecoxib; MCF7; Pharmacological interaction; Apoptosis; Cell cycle.

Dept. of Tumor Pathology

195. Chapter 7: Schistosomasis and Bladder Cancer

Saad S. Eissa, M. Nabil El-Bolkainy and Mohab S. Eissa

66www.gsrd.cu.edu.eg

Vol. 6 (2), Oct.2012

Schistosomasis InTech Open access, (2011)

Schistosomiasis also known as bilharziasis is a parasitic disease that dates back to antiquity. The ancient Egyptians, through settling and cultivating the Nile valley, were among the first to contract the disease. Thus, the main symptom hematuria was mentioned in Egyptian papyri (1500-1800 B.C.), and schistosome eggs were identified in Egyptian mummies through paleopathologic studies. In 1852, Theodor Bilharz, a German pathologist working in Cairo, discovered the worms in the portal circulation and was the first to describe the Pathology of the disease. Ferguson in 1911 was the first to report on the high frequency of bladder cancer in Egypt and to suggest an etiologic relation with urinary Schistosomiasis, a fact which is now generally accepted (Bolkainy & Chu 1981a). The aim of this article is to review the pathobiology of Schistosoma associated bladder cancer (SACB), describe the relationship between Schistiosomiasis and bladder cancer with respect to the mechanisms of carcinogenesis with emphasis on special features of SABC and recent methods of early detection.

67www.gsrd.cu.edu.eg