2006 ISSN : 0959-4973 Impact Factor: 1.907 Journal: ANTI-CANCER DRUGS (2006) Phase II, Open-Label, Randomized Study (SIGN) of Single-Agent Gefitinib (IRESSA) or Docetaxel As Second-Line Therapy in Patients with Advanced Stage Lllb or IV Non-Small-Cell Lung Cancer Tanja Cufera*, Eduard Vrdoljakb**, Rabab Gaafar*** Inci Erensoy and Kristine Pemberton**** on behalf of the SIGN study group Abstract Our objective was to evaluate gefitinib (lRESSA), an epidermal growth factor receptor tyrosine kinase inhibitor, versus docetaxel as second- line monotherapy for advanced non- small-celllung cancer (NSCLC). SIGN (Second-line Indication of Gefitinib in NSCLC; code 1839IL/0503) was a multicenter, randomized, parallel-group, open-label, phase 11 trial that investigated oral gefitinib (250 mg/day) or i.v. docetaxel (75 mg/m2 every 3 weeks) in patients with advanced NSCLC who had previously received one chemotherapy regimen. The primary objective was assessment of symptom improvement (using the FACT-L Lung Cancer Subscale). Secondary objectives included quality of life (FACT-L total score), response rate (using RECIST>, overall survival and safety. This trial recruited 141 patients (68 to gefitinib and 73 to docetaxel) who received treatment for a median duration of 3.0 (gefitinib) and 2.8 (docetaxel) months. Similar efficacy was observed with gefitinib and docetaxel, 36.8 and 26.0% symptom improvement rates, 33.8 and 26.0% quality-of-life improvement rates, 13.2 and 13.7% objective response rates, and 7.5 and 7.1 months median overall survival, respectively. Fewer drug-related adverse events were observed with gefitinib compared with docetaxel (all grades: 51.5 versus 78.9%; Common Toxicity Criteria grade 3/4: 8.8 versus 25.4%). There were no withdrawals or deaths due to drug-related adverse events with gefitinib, while three patients withdrew and three died due to adverse events in the docetaxel group that were possibly drug related. We conclude efficacy with gefitinib was similar to docetaxel, but with a more favorable tolerability profile, in the second-line treatment of
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2006ISSN : 0959-4973 Impact Factor: 1.907
Journal: ANTI-CANCER DRUGS (2006)Phase II, Open-Label, Randomized Study (SIGN) of Single-Agent Gefitinib (IRESSA) or Docetaxel As Second-Line Therapy in Patients with Advanced Stage Lllb or IV Non-Small-Cell Lung CancerTanja Cufera*, Eduard Vrdoljakb**, Rabab Gaafar*** Inci Erensoy and Kristine Pemberton**** on behalf of the SIGN study groupAbstractOur objective was to evaluate gefitinib (lRESSA), an epidermal growth factor receptor tyrosine kinase inhibitor, versus docetaxel as second-line monotherapy for advanced non- small-celllung cancer (NSCLC). SIGN (Second-line Indication of Gefitinib in NSCLC; code 1839IL/0503) was a multicenter, randomized, parallel-group, open-label, phase 11 trial that investigated oral gefitinib (250 mg/day) or i.v. docetaxel (75 mg/m2 every 3 weeks) in patients with advanced NSCLC who had previously received one chemotherapy regimen. The primary objective was assessment of symptom improvement (using the FACT-L Lung Cancer Subscale). Secondary objectives included quality of life (FACT-L total score), response rate (using RECIST>, overall survival and safety. This trial recruited 141 patients (68 to gefitinib and 73 to docetaxel) who received treatment for a median duration of 3.0 (gefitinib) and 2.8 (docetaxel) months. Similar efficacy was observed with gefitinib and docetaxel, 36.8 and 26.0% symptom improvement rates, 33.8 and 26.0% quality-of-life improvement rates, 13.2 and 13.7% objective response rates, and 7.5 and 7.1 months median overall survival, respectively. Fewer drug-related adverse events were observed with gefitinib compared with docetaxel (all grades: 51.5 versus 78.9%; Common Toxicity Criteria grade 3/4: 8.8 versus 25.4%). There were no withdrawals or deaths due to drug-related adverse events with gefitinib, while three patients withdrew and three died due to adverse events in the docetaxel group that were possibly drug related. We conclude efficacy with gefitinib was similar to docetaxel, but with a more favorable tolerability profile, in the second-line treatment of advanced NSCLC. These results support further investigation of gefitinib in this disease setting.KeywordsDocetaxel; Epidermal Growth Factor Receptor; Gefitinib.Non-Small-Celllung Cancer; Second-Line Therapy; EGFR Tyrosine Kinase Inhibitor.ISSN : 0732-183X Impact Factor: 11.81
Journal: Journal of clinical oncology (2006)Short-Term Treatment-Related Symptoms and Quality of Life: Results from an International Randomized in Patients with Malignant Pleural Mesothelioma: an EORC Lung Cancer Group and National Cancer Institute, Canada, Intergroup Studyndrew Bottomley, Rabab Gaafar, Christian Manegold, Sjaak Burgers, Corneel Coens, Catherine Legrand, Mark Vincent, Giuseppe Giaccone, and Jan Van Meerbeeck
AbstractPurpose: For malignant pleural mesothelioma (MPM) patients with a poor prognosis, maintaining health- related quality of life (HRQOL) is important. This article compares the impact on HRQOL of first-line treatment with cisplatin versus raltitrexed and cisplatin. Patients and Method: Patients with histologically-proven unresectable MPM, not pretreated with chemotherapy were randomly assigned to receive cisplatin 80 mg/m2 intravenously on day 1, with or without preceding infusion of raltitrexed 3 mg/m2. HRQOL was assessed with the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30) and EORTC Lung Cancer Module (QLQ-LC13) tools. Assessments were conducted at baseline, immediately before every treatment cycle, at the end of treatment, and every six weeks for 12 months. Results: Two hundred fifty patients were randomly assigned, 80% were male with a median age of 58 years, WHO performance status 0, 1, and 2, in 25%, 62%, and 13% of cases. The clinical results found raltitrexed and cisplatin to be superior to cisplatin with regard to overall survival (P. 048). The global HRQOL scale was comparable at baseline on both treatment arms (P. 848); at no point was any significant difference apparent on this end point. Both treatments led to an improvement, over time, in dyspnoea. This effect is an important clinically meaningful reduction from baseline in the cisplatin/raltitrexed arm. However, the majority of scales of the EORTC QLQ-C30 or LC13 showed stabilization of HRQOL with few clinically significant differences between the treatment arms. Conclusion: This study provides important information about the HRQOL of chemotherapy-treated MPM patients.
ISSN : 1352-0504 Impact Factor: 2.54Journal: Journal of Viral Hepatitis 98 (2006)Immunomodulators, sFas and Fas-L as potential noninvasive predictors of IFN treatment in patients with HCV genotype-4A. R. N. Zekri,1 H. A. Haleem,2 G. E. -D. Esmat,2 A. A. Bahnassy,3 H. M. A. El-Din,1M. M. Hafez,1 A. F. Sharaby,2 H. Sharaf4 and M. S. E.-D. Zakaria2AbstractRecent studies have indicated that cytokines can be used as markers for disease progression in hepatitis C virus (HCV)-infected patients, therefore this study was conducted to determine the influence of pegylated IFN vs standard IFN on interleukin-2 receptor (IL-2R), IL-6R, IL-8, TNFR-I, TNFR-II, sFas, and sFas-L in Egyptian patients with chronic hepatitis C genotype 4, as no previous studies have been performed on this genotype. We also aim at estab- lishing a possible relationship between these cytokines and the response to INF to determine whether they can be used as noninvasive markers for the response to INF therapy and as monitors for the outcome of treatment. Thirty-eight patients with chronic HCV hepatitis were investigated for the serum levels of the previously mentioned cytokines in a randomized opened controlled trial (22 patients treated with pegylated IFN and 16 patients treated with standard IFN). Cytokine levels were measured by ELISA at 0, 1 and12 months of IFN therapy. There was marked increase in the serum levels of IL-2R and IL-6R in nonresponders to pegylated interferon, IL-8, TNFR-I and II were significantly higher in nonresponders to standard interferon but were also high in responders of pegylated interferon. sFas and sFas-L showed high levels among responders to pegylated
interferon but the standard interferon was again less effective in this regard. Serum levels of TNFR-II, sFas and sFas-L have the potential to be used as serological markers for response to pegylated IFN therapy, and IL-8 is a pre- dictor for nonresponse. Moreover, TNFR-I and II have the potential to be used as markers of response to standard IFN treatment. The persistent correlation between sFas and TNFR-II may elaborate the possible role of pegylated IFN in the induction of apoptosis as a possible new mechanism of viral clearance during treatment with pegylated interferon treatment.KeywordsHCV, genotype-4, IFN, sFas, Fas-L, TNFR.Journal: Histopathology 48 516-528 (2006)
Epstein.Barr viral infection in extranodal lymphoma of the head and neck: correlation with prognosis and response to treatmentA. A. Bahnassy, A-R N Zekri,1 N Asaad,2 S El-Houssini, H M Khalid,3 L M Sedky4 & N M Mokhtar AbstractAims: To determine the prevalence of Epstein.Barr virus (EBV) infection in primary extranodal lymphoma of the head and neck (PELHN) in immunocompetent patients.PELHN represents 16.18% of all lymph- oma diagnosed at the National Cancer Institute, Cairo. Although EBV infection is highly associated with lymphoma in immunocompromised patients, the situation in immunocompetent patients is still unclear. Material and methods: The study included 50 PELHN (11 cases in the nose and paranasal sinuses, 11 in the nasopharynx, 13 in the tonsils, seven in the orophar- ynx and eight in the oral cavity), five reactive lymph nodes, 15 normal nasopharyngeal tissue and 25 throat washes of healthy subjects from Egypt. Cases and controls were assessed for the presence of EBV by polymerase chain reaction (PCR) and in situ hybridiza- tion techniques, the presence of 30 base pair deletion of the LMP-1 (del-LMP1) gene and for the expression of p53, Ki67, bcl-2 and Bax by immunohistochemistry. This was alsocorrelated with the clinical outcome of patients.Results: EBV was detected in 90% and 70% of the cases using EBER in situ hybridization and PCR, respec- tively. All cases of nasal type lymphoma were positive for EBV. del-LMP1 gene was detected in 24 O 35 of EBV+ cases (68.6%), whereas 11 cases had wild-type variant either alone or mixed with del-LMP1. There was a significant difference in the frequency of del-LMP1 between lymphoma and normal tissues. Overexpres- sion of Ki67, p53 and bcl-2 was detected in 78.1%,62.5% and 20% of cases, whereas loss of Bax was detected in 18% of the cases. Multivariate analysis showed that only p53 overexpression, del-LMP1 vari- ant and advanced disease stage are independent prognostic factors.Conclusion: EBV infection is frequent in PELHN in Egypt. Possible pathogenic mechanisms involve de- regulation of p53 and enhanced proliferation (as detected by high Ki67 index). The presence of del- LMP1 variants, p53 overexpression and advanced disease stage are poor prognostic factors associ- ated with reduced survival and poor response to therapy.Keywords: bcl-2 and Bax, EBV, head and neck, Ki67, lymphoma, p53.
ISSN : 1464-4096 Impact Factor: 2.247
Journal: BJU INTERNATIONAL (2006) Ileocaecal Vs Ileal Neobladder After Radical Cystectomy in Patients with Bladder Cancer: A Comparative Study MEDHAT KHAFAGY, FOUAD ABDEL SHAHEED AND TAREK ABDEL MONEIMAbstractOBJECTIVETo compare an ileocaecal orthotopic bladder, (which has been the standard procedure in Egypt for >30 years) with the ileal neobladder, as there is no ideal continent orthotopic bladder replacement for patients after cystectomy for bladder cancer.PATIENTS AND METHODS Between June 1999 and December 2001, 60 patients with invasive bladder cancer were randomized into two groups. Group A comprised 29 patients who had radical cystectomy and reconstruction with an ileal neobladder (median age 50 years, 27 men and two women) and group B included 31 who had an ileocaecal bladder substitution after radical cystectomy (median age 51 years, 28 men and three women). RESULTS The complication rate after surgery in group A was 17%, with two deaths, one from acute myocardial infarction and the other from haematemesis. In group B, the complication the patients in group A but in none in group B (P < 0.05). The pelvicalyceal systems were preserved in 85% of patients in group A and 93% in group B during the 2-year follow-up. The mean (SD) renal cortical thickness was less in group A than in group B, at 1.8 (0.5) and1.9 (0.2) cm, respectively. Although the cystometric capacity was greater and the basal pressure less in group A than B, these were not reflected in the degree of diurnal and nocturnal continence or back pressure on the renal units. CONCLUSION Continence in both pouches was similar but the renal units were preserved better in the ileocaecal than in the ileal neobladder. Residual urine volume was greater in the ileal neobladder, with its potential complications of infection and stone formation, and acidosis was more evident. KeywordsUrinary Diversion; Cystectomy; Urinary Reservoirs; Ileocaecal; Continence; Ileal Neobladder.ISSN : 1369-3786 Impact Factor: 1.422
Journal: Medical Mycology 44 733-739 (2006) Evaluation of Pan-Fungal PCR Assay and Aspergillus Antigen Detection in The Diagnosis of Invasive Fungal Infections in High Risk Paediatric Cancer Patients Hadir A. El-Mahallawy, Heba H. Shaker, *Hala Ali Helmy, Tarek Mostafa, **Abdel Razak Abo-SedahAbstractBackground and purpose: Profound and prolonged neutropenia following chemotherapy is a major risk factor for systemic fungal infection. As the early diagnosis of invasive fungal infection (IFI) is difficult, these infections are still associated with high morbidity and mortality. Recently, Pan-fungal polymerase chain reaction (PCR) has been a promising aid in rapid, early diagnosis of IFI. During the past few years, increasing numbers of suspected IFIs are encountered at our institution in patients with prolonged neutropenia after intensified immunosuppressive hemotherapy. The aim of this study was to investigate the diagnostic utility of both the aspergillus galactomannan (GM) antigen and the panfungal PCR assay in the diagnosis of IFI in high risk febrile neutropenic paediatric cancer patients. Patients and methods: During one year period, 91 febrile neutropenic (FN) paediatric cases at high risk for developing IFI while
receiving chemotherapy were investigated at National Cancer Institute, Egypt. These patients were subjected to clinical evaluation, chest CT scan, conventional blood cultures for bacterial and fungal pathogens, aspergillus GM antigen detection and PCR assay utilizing pan-fungal primers. Results: Of the 91 FN episodes, 15 were proven IFI; whereas 27 cases were either probable (n= 13) or possible IFI (n= 14), and 49 were unlikely to be IFI episodes. Based on positive results for proven/probable IFI and compared to culture results, Pan-fungal PCR showed sensitivity, specificity, positive and negative predictive values of 75%, 92%, 84% and 87%; respectively. Aspergillus antigen test showed a sensitivity of 79%, specificity of 61%, positive and negative predictive values of 54% and 83%; respectively. A negative PCR in the proven and probable cases was closely related to previous antifungal therapy for a rior history of IFI.Conclusions: In patients at high risk for IFI, the results of PCR assay correlated well with the diagnosis of IFI. The PCR test is more specific than the GM test for screening high risk group cancer patients in a hospital laboratory. The specificity of GM test is not sufficient and can be improved by PCR. The PCR assay seems more promising than the GM test for objectively defining IFI. The main value of the simultaneous use of these tests is to confirm the diagnosis. Therefore, when positive, these tests could provide an alternative to invasive investigations such as lung biopsyKeywordsInvasive fungal infection IFI; Haemato-oncology patients; Polymerase ahain reaction PCR; Galactomannan GM; Aspergillus antigen.ISSN : 0743-684X Impact Factor : 0.55Journal : Reconstructive Microsurgery 22 No 2 97-104 (2006) Free Anterolateral Thigh Flap for Reconstruction of Major Craniofacial Defects Ayman Amin, M.D. , Mohammed Rifaat, M.D., FRCS , Francisco Civantos, M.D. , Donald Weed, M.D. , Mohammed Abu-Sedira, M.D. andMahmoud Bassiouny, M.D.Abstract :Free-tissue transfer has revolutionized skull-base surgery by expanding the ability to perform cranial base resection and by improving the quality of reconstruction. The anterolateral thigh flap has come recently into use in the field of head and neck reconstruction. Its role in craniofacial and midface reconstruction has not been specifically defined. This study involved a total of 18 patients who were treated over a 5-year period from 1998 to 2003. Seventeen patients had locally advanced head and neck cancer, requiring craniofacial resection, and one patient had a complicated gun shot wound of the forehead. Thirteen patients were treated at the National Cancer Institute, Cairo University, Egypt, and five patients at the University of Miami,Florida. The patients presented with defects of the anterior skull base (5), lateral skull base (3), scalp and calvarium (3), and the midface (7). The anterolateral thigh flap was used as a myocutaneous flap in 11 cases and as a perforator fasciocutaneous flap in seven cases. Musculocutaneous perforators supplied the majority of flaps (17/18). Total flap survival occurred in 17 cases; one patient developed complete flap necrosis. The most commonly used reciepient vessels were the facial vessels and the external jugular vein. Major complications included one case with meningitis; the patient died after failure of treatment. Another patient died 6 weeks postoperatively from pulmonary embolism. One patient developed CSF leak that stopped spontaneously. In addition, two patients developed minor wound dehiscence that healed spontaneously. The donor-site wound healed without problems except in two
cases. One patient had an incomplete take of the skin graft; the other developed wound infection and superficial sloughing. Both wounds healed spontaneously. In addition to the feasibility of simultaneous flap harvesting with tumor resection, the flap’s advantage in skull base reconstruction is its reliable blood supply, which can provide adequate dural cover and protection of the brain. Its size and moderate thickness are suitable for reconstruction of scalp and calvarial defects. The abundance of reliably vascularized fat in the flap may be an advantage in long-term maintenance of the volume of the flapin midface reconstruction. Similar to other soft tissue flaps, additional skeletal reconstruction may still be required to achieve an optimal functional and aesthetic result.
Dep. : Cancer Biology Name : Prof . Abdel-Rahman Nabawy Zekri
ISSN : 1320-5463 Impact Factor : 1.108 Journal : Pathology Evaluation of Simian Virus-40 as a Biological Prognostic Factor in Egyptian Patients with Malignant Pleural MesotheliomaAbdel-Rahman N. Zekri, Abeer A. Bahnassy, Waleed S. Mohamed, Nelly assan,Abdel-Rahman M. Abdel-Rahman, Fatma Abou El-Kassem and Rabab GaafarAbstract :The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an etiological role for SV40. However, exact pathogenetic mechanisms and pos- sible prognostic value are not clear. The purpose of the present paper was to investigate 40 Egyptian MPM patients for the presence of SV40 DNA, altered Rb expression and p53 gene status using immunohistochemistry and molecu- lar techniques. The relation between SV40, asbestos expo- sure, Rb, p53 and their contribution to the overall survival (OS) were also assessed. SV40 DNA was detected in 20/40 patients and asbestos exposure in 31 patients; 18 of them were SV40 positive. Altered p53 and Rb expression were detected in 57.5% and 52.5%, respectively, with no p53 mutation. Univariate analysis showed a significant correla- tion between OS and stage (P = 0.03), performance status (P = 0.04), p53 overexpression (P = 0.05), asbestos expo- sure (P = 0.002) and SV40 (P = 0.001). Multivariate analysis showed that when SV40 and asbestos exposure were con- sidered together, only combined positivity of both was an independent prognostic factor affecting the OS (P = 0.001). SV40 and asbestos exposure are common in Egyptian MPM, denoting a possible etiological role and a synergistic effect for both agents. Combined positivity for SV40 and asbestos exposure is an independent prognostic factor in MPM, having a detrimental effect on OS.KeywordsAsbestos; Malignant Pleural Mesotheliom; P53; Rb; Sv40
Dept.: Tumor Biology
Title : Androgen Profiles Among Egyptian Adults Considering Liver
StatusCristina E Aguilar, Amr S Soliman, Daniel S McConnell, Abdel-Rahman Zekri, Mousumi Banerjee, Ayman Omar, Mohamed Sharawy, Sherif Omar, Ahmed Raouf and MaryFran R SowersJournal: Gastroenterology and HepatologyISSN: 0815-9319 Impact Factor: 1.785Abstract:Background and Aim: Hepatitis C virus (HCV) and environmental hepatotoxins may have an indirect influence on health by altering the synthesis and function of hormones, particularly reproductive hormones. We aimed to evaluate liver diseases and sex steroid hormones in Egypt, which has the highest prevalence of HCV worldwide. Methods: We measured markers of hepatitis B virus (HBV), HCV and schistosomiasis infection as well as liver function in 159 apparently healthy subjects. We measured total testosterone (T), sex-hormone binding globulin (SHBG) and albumin, and calculated the free androgen index. Results: Anti-HCV antibodies were detected in 51 % of men and 42% of women. Based on HCV reverse transcription PCR (RT-PCR) of 44 men and 33 women, 11 % of men and 21 % of women
showed HCV viremia. There was schistosomiasis in 25% of men and 9% of women, and mixed HCV viremia and schistosomiasis in 57% of men and 52% of women. Compared with men with schistosomiasis only (mean 593.3 ± 73.4 ng/dl.), T was higher in men with mixed HCV viremia and schistosomiasis (mean 854.5 ± 47.9 ng/dL; P = 0.006) and men with mixed chronic HCV and schistosomiasis (mean 812.1 ± 43.3 ng/dL; P = 0.001). Men with mixed chronic HCV and schistosomiasis had also significantly higher SHBG (mean 57.7 ± 3.9 ng/dL) than males with schistosomiasis only (mean 34.8 ± SE 4.5 ng/dL; P = 0.0003). Conclusion: Future investigations should consider that a high prevalence of asymptomatic liver disease may alter associations between hormone concentrations and chronic disease etiology.Keywords:Androgen; Egypt; Hepatitis; Hormones; Lliver.
ISSN : 1743-422X Impact Factor : 1.94
Journal : Virology Hepatitis B Virus (HBV) Genotypes in Egyptian Pediatric Cancer Patients with Acute and Chronic Active HBV InfectionAbdel-Rahman N Zekri, Mohamed M Hafez, Nahed I Mohamed, Zeinab K Hassan, Manal H El-Sayed, Mohsen M Khaled and Tarek MansourAbstract :Background: There are eight genotypes of hepatitis B virus (A-H) and subgenotypes are recognized. Genotyping can be accomplished based on a partial sequence of HBV genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping. This study was undertaken to determine the HBV genotypes in Egyptian pediatric cancer patients with acute and chronic liver disease. Methods: HBV genotypes were determined in 22 patients who had acute forms of liver disease (AH) and in 48 patients with chronic active hepatitis (CAH). A type-specific primer based the nested-PCR method was employed in the HBV genotyping. Results: This study showed that HBV infections in pediatric cancer patients are attributed predominantly to viral genotypes D and B that constituted 37.1% and 25.7%, respectively of the total infections. In addition, there was a relatively high prevalence of mixed infections of 15.7% among the studied group especially mixed A/D genotype infections. Genotype D was found significantly more often in patients with CAH than in patients with AH [23/48 (47.9%) v 3/22 (13.6%)]. Conclusion: These findings show the distribution of HBV A-D genotypes in pediatric cancer Egyptian patients. Furthermore,our results indicate a markedly high prevalence of mixed A/D genotype infections in subjects with CAH and a possible association of mixed infections with the severity of liver diseases.Dep. : Clinical Pathology Name : Dr . Abeer Ahmed Bahnassy
ISSN : 1024-8194 Impact Factor : 1.559
Journal : Leukemia & Lymphoma Detection of Simian Virus 40 DNA Sequences in Egyptian Patients with Different Hematological MalignanciesAbdel-Rahman Zekri, Waleed Mohamed, Abeer A. Bahnassy, Lobna Refit,Mohsen Khaled, Sameh Shalaby and Mohamed Hafez
bstract :SV40 DNA sequences have been detected in non-Hodgkin.s lymphoma patients A link between SV40 and NHL is biologically plausible since SV40 causes hematological malignancies in laboratory rodents. We investigated 266 Egyptian cases of hematological malignancies (158 NHL, 54 HD, 26 ALL, 13 AML, 8 CLL, 7 CML) and 34 subjects as a control for detection of SV40 DNA using nested PCR. SV40 DNA sequences were found in (53.8%) of NHL, (29.6%) of HD and in (40.7%) of different types of leukemia cases. Frequency of SV40 DNA sequences was higher in NHL patients compared with those with the other tumors and control group ( p < 0.05 ). The highest frequency was in Burkitt.s lymphoma followed by diffuse large B-cell lymphoma. The present study suggests that SV40 is significantly associated with non-Hodgkin.s lymphoma and most probably acts as a cofactor in the pathogenesis of these tumors. This could lead to new diagnostic, therapeutic, and preventive approaches.Keywords : SV40 DNA; Hematological malignancies; Egypt
ISSN : 1743-422X Impact Factor : 1.94
Journal : Virology Genetic Distance and Heterogenecity Between Quasispecies is A Critical Predictor to IFN Response in Egyptian Patients with HCV Genotype-4Abdel-Rahman Zekri, Waleed Mohamed, Abeer A. Bahnassy, Lobna Refat, Mohsen Khaled, Sameh Shalaby and Mohamed HafezAbstract :Background: HCV is one of the major health problems in Egypt, where it is highly prevalent. Genotype4 is the most common genotype of HCV and its response to treatment is still a controversy. Methods: HCV genotype 4 quasispecies diversity within the 5' untranslated region (5'UTR) was studied in a series of 22 native Egyptian patients with chronic hepatitis C virus with no previous treatment who satisfied all NIH criteria for combined treatment of pegylated IFN and ribavirine and was correlated with the outcome of treatment. The study also included 7 control patients with no antiviral treatment. HCV sequencing was done using the TRUGENE HCV 5-NC genotyping kit.Results: At the 48th week of treatment, 15 patients (68%) showed virological response. Whereas HCV- RNA was still detected in 7 patients (32%) in this period; of those, 6 experienced a partial virological response followed by viral breakthrough during treatment. Only one patient did not show any virological or chemical response. The four females included in this study were all responders. There was a significant correlation between the response rate and lower fibrosis (p = 0.026) as well as the total number of mutation spots (including all the insertions, deletions, transitions and transversions) (p = 0.007, p = 0.035 ). Conclusion: Patients who responded to interferon treatment had statistically significant less number in both transitions (p = 0.007 ) and the genetic distances between the quasispecies (p = 0.035 ). So, viral genetic complexity and variability may play a role in the response to IFN treatment. The consensus alignment of all three groups revealed no characteristic pattern among the three groups. However, the G to A transitions at 160 was observed among non responders who need further study to confirm thisobservation.ISSN : 0021-9746 Impact Factor : 2.245
Journal : BMC Clinical Pathology The Possible Role of Cell Cycle Regulators in Multistep Process of HPV-Associated Cervical CarcinomaAbeer A. Bahnassy, Abdel Rahman N Zekri, Maha Saleh, Mohammad Lotayef, Manar Moneir and Osama ShawkiAbstract :Background: Human papillomavirus (HPV) 16 and 18 are associated with cervical carcinogenesis through an interaction between HPV oncogenic proteins and cell cycle regulatory genes. However, the exact pathogenetic mechanisms are not determined yet. Methods: We investigated 43 invasive squamous cell carcinoma (ISCC), 38 CIN III, 11 CINII and18 CINI for cyclin D1, cyclin E, CDK4, p53, mdm-2, p21waf, p27, p16INK4A, Rb and Ki-67 aberrations using immunohistochemistry and molecular techniques. Twenty samples of normal cervical tissues(NCT) were taken as a control. Results: There was a significant increase in the expression of Ki-67, cyclin E, CDK4, p16INK4A, Rb (p=0.003, 0.001, 0.001, 0.01) and a significant decrease in p27KIP1 from NCT to ISCC (p = 0.003). Increased cyclin D1, p21waf, p53, mdm-2 expression, homozygous deletion (HZD) and promoter methylation (PM) of the Rb were detected in CINIII and ISCC only. On univariate analysis; tumor size, differentiation, lymph node status, FIGO stage, Ki- 67, cyclin D1, p53 and p27KIP1 are significantly associated with reduced overall survival (OS) while on multivariate analysis; only FIGO stage, Ki-67, cyclin D1, p53 and p27KIP1 were significant. Conclusion: 1) Aberrations involving p27KIP1, cyclin E, CDK4, p16INK4A are considered early events in HPV 16 and 18-associated cervical carcinoma, whereas cyclin D1 and p53 pathway abnormalities are considered late events. 2) Immunohistochemical tests for p16INK4Aand cyclin E, could help in early diagnosis of cervical carcinoma. 3) Only FIGO stage p53, cyclin D1, p27KIP1 and Ki-67 are independent prognostic factors that might help in predicting outcome of cervical cancer patients.Title : The Diagnostic Value of C-reactive Protein, Interleukin-8, and Monocyte Chemotactic Protein in Risk Stratification of Febrile Neutropenic Children with Hematologic Malignancies
Nabil M. Ahmed, Hadir El-Mahallawy, Ibrahim A. Ahmed, Shimaa Nassif, Aamal El- Beshlawy and Alaa El-Haddad Nabil AhmedJournal: Pediatr Hematol OncolISSN: 0888-0078 Impact Factor: 0.529Abstract:Background and Aim: Recent advances in febrile neutropenia have highlighted the value of risk stratification especially that it can have important implications in terms of management. We aimed to identify a serum marker that may help to stratify febrile neutropenic pediatric patients treated for hematologic malignancies at the time of first evaluation. Thus, Creactive protein (CRP), interleukin-8 (IL-8), and monocyte chemotactic protein-1-α (MCP-1-α) were evaluated for their predictive and diagnostic relevance in febrile episodes of cancer patients. Patients and Methods: Within 24 hours of fever, CRP, IL-8, and MCP-1 serum levels were measured and the levels of these markers were related to the clinical findings of the patients. For this purpose, we collected and analyzed clinical data of 85 fever episodes occurring in 76 patients with hematologic malignan- cies, presenting to the Department of Pediatric Oncology, National Cancer Institute, Cairo University, during a 6-month period. Results: Neutropenic children with febrile episodes were classified into 2 groups, a group with unexplainable fever (group I, n
= 26) and another group with either blood culture positive, and/or fever periods with a documented clinical sepsis and/or local infection (group II, n = 59). Clinically, local sites of infection were encountered in 39 cases (45.9%), whereas a positive blood culture was detected in 20 cases. CRP, IL-8, and MCP-1 levels were significantly lower in group I versus group II (P value < 0.001). There were overlaps of values between groups. CRP ≥ 90 mg/L was significantly associated with chemotherapy-related neutropenia and fever owing to bacter- emia (P = 0.038). The sensitivity, specificity, negative and positive predictive values of CRP, MCP-1, and IL-8 were (70%, 73%, 51%, and 85%), (64%, 92%, 53%, and 95%), and (71%, 77%, 54%, and 88%), respectively. Combining 2 or 3 markers improved the diagnostic performance of these test, as78% of group II had elevated 2 or 3 markers versus 16% of the group with no evident infection. Conclusions: Low levels of CRP, MCP-1, and IL-8 could identify patients with unexplainable fever; whereas, high levels of these markers were of help in the diagnosis of infectious episodes. A model combining more than 1 marker is recommended in the assessment of febrile neutropenia.Keywords:Febrile neutropenia; Hematological malignancies; C-reactive protein (CRP); Interleukin 8(IL-8); Monocyte chemotactic protein 1 alpha (MCP-1)
ISSN : 1545-5009 Impact Factor : 1.882
Journal : Pediatric Blood Cancer Early Hospital Discharge Versus Continued Hospitalization in Febrile Pediatric Cancer Patients with Prolonged Neutropenia: A Randomized, Prospective StudyNabil M. Ahmed, Hadir A. El-Mahallawy, Ibrahim A. Ahmed, Shimaa Nassif, Aamal El-Beshlawy and Alaa El-Haddad Nabil Ahmed Abstract :Purpose: Hospitalization with single or multi-agent antibiotic therapy has been the standard of care for treatment of high-risk febrile neutropenia. We hypothesize that an empiric antibiotic regimen that is effective and that can be administered once daily will allow for improved hospital utilization by early transition to outpatient care. Patients and Methods: Patients were randomized between a regimen of once daily ceftriaxone plus amikacin (C+A) and imipenem monotherapy (control). Afebrile patients on C+A satisfying .Early Discharge Criteria. at 72 hours continued treatment as outpatients. We compared the outcome, adverse events, duration of hospitalization and cost between both groups. Intention-to-treat analysis was used. Results: A prospective randomized controlled clinical trial of 119 pediatric cancer patients with high-risk fever and neutropenia was conducted. We found a statistically significant difference between the duration of hospitalization of the C+A group [median 5 days] and control [median 9 days] (p<0.001), per episode antibiotic cost (p< 0.001) and total episode cost (p< 0.001). Similar results were obtained using estimated costs in a corresponding North American institution. There was no statistically significant difference in the response to treatment at 72 hours, or after necessary antimicrobial modifications. Conclusion: We conclude that pediatric febrile-neutropenic patients initially at considered at .high risk. for sepsis can be reevaluated at 72 hours for outpatient therapy. The convenience, low incidence of adverse effects and cost benefit of the once daily regimen of ceftriaxone plus amikacin will be particularly useful to reduce the overall treatment costs, and duration of hospitalization.
Name : Prof . Hussein Mostafa KhaledISSN : 0885-3177 Impact Factor : 2.121Journal : Pancreas Lifestyle, Occupational, and Reproductive Factors in Relation to Pancreatic Cancer RiskAn-Chi Lo , Amr S. Soliman, , Nabih El-Ghawalby ,Mohamed Abdel-Wahab ,Omar Fathy, Hussein M. Khaled ,Sherif Omar, Stanley R. Hamilton, Joel K. Greenson and James L. AbbruzzeseAbstract :Objectives: This study examined the epidemiology of pancreatic cancer in Egypt. Methods: We obtained detailed information on smoking, occupa- tional, medical, and reproductive histories from 194 pancreatic cancer cases and 194 controls. Results: Compared with not smoking, smoking cigarettes alone or in conjunction with other smoking methods (eg, water pipe, cigar) was associated with an increased risk (odds ratio [OR], 4.5 and 7.8; 95% confidence interval [95% CI], 1.9Y10.7 and 3.0Y20.6, respectively). Passive smoking was also a significant risk factor (OR, 6.0; 95% CI,2.4Y14.8). The risk of pancreatic cancer was elevated among subjects exposed to pesticides (OR, 2.6; 95% CI, 0.97Y7.2). A prior diagnosis of diabetes mellitus for a period of 10 years was associated with higher risk (OR, 5.4; 95% CI, 1.5Y19.9). For women, having 7 or more live births and lactating for 144 months or longer were associated with a reduced risk (OR, 0.5 and 0.2; 95% CI, 0.2Y1.3 and 0.1Y0.9, respectively). No association was found between family history, allergy, or obesity and pancreatic cancer in Egypt. Conclusions: Multiple tobacco consumption methods, passive smoking, pesticide exposures, and diabetes are associated with an increased risk for pancreatic cancer. Prolonged lactation and increased parity are associated with a reduced risk for pancreatic cancer. Keywords : Pancreatic Cancer; Lifestyle; Occupation; ReproductiveFactors; Risk Factors.
ISSN : 0167-6806 Impact Factor : 4.671Journal : Breast Cancer Research Treatment Molecular epidemiologic features of inflammatory breast cancer: A Comparison Between Egyptian and US PatientsAn-Chi Lo, Celina G. Kleer, Mousumi Banerjee,Sherif Omar, Hussein M. Khaled ,Saad Eissa, Ahmed Hablas, Julie A. Douglas , Sharon H. Alford Sofia D. Merajver and Amr S. SolimanAbstract :Background: Inflammatory breast cancer (IBC) is a lethal form of breast cancer with unknown etiology. A higher frequency of IBC and a more aggressive IBC phenotype was reported in Egypt than in the United States. This difference in disease frequency and presentation might be related to molecular epidemiologic factors. Methods: We used tumor blocks and demographic, epide- miologic, and clinical data of 48 IBC patients from Egypt and 12 patients from the United States. We counted tumor emboli in tumors before and after immunohistochemical staining with lymphatic vessel endothelial receptor-1 (LYVE-1), and measured the expression of RhoC GTPase protein in the two groups. Results: Erythema,
edema, and peau d.orange were found in 77% of the Egyptian patients as compared with 29% found in the US patients ( P = 0.02 ). The number of tumor emboli was significantly higher in tumors from Egypt (mean ± SD, 14.1 ± 14.0 ) than in the tumors from the United States (5.0 ± 4.0, P = 0.01 ). The number of tumor emboli in LYVE-1 positive vessels was higher in tumors from Egypt (3.5 ± 2.8 ) than tumors from the United States (1.6 ± 0.5, P = 0.15 ). We detected a high level of RhoC in 87% of the tumors from Egypt and 14% of the tumors from the United States (P = 0.0003 ). Conclusion: Patients from Egypt have a more aggressive form of IBC than those in the United States. Our analysis of IBC patients shows that distinct molecular phenotypes can be found when these two study populations are compared. Future studies should explore the epidemiologic and environmental exposures and the genetic factors that might lead to the different clinical and molecular features of IBC in patients from these two countries.Keywords : Inflammatory Breast Cancer; Tumor Emboli; RhoC; LYVE-1; Molecular Epidemiology;International.
ISSN : 0143-3334 Impact Factor : 5.366
Journal : CarcinogenesisDifferences in K-ras and p53 Gene Mutations Among Pancreatic Adenocarcinomas Associated with Regional Environmental pollutionAmr S.Soliman , An-Chi Lo, Mousumi Banerjee, Nabih El-Ghawalby,Hussein M.Khaled, Sherif Bayoumi, Ibrahim A.Seifeldin, Atef Abdel-Aziz,James L.Abbruzzese, Joel K.Greenson and Stanley R.HamiltonAbstract :Background: Variations in genetic mutations in pancreatic carci- noma between different geographical regions have not been stud- ied extensively, especially in developing countries where pancreatic cancer is relatively rare. Methods: We studied the mo- lecular pathology of 54 pancreatic adenocarcinomas from Egyp- tian patients residing in a heavily polluted region of the eastern Nile River delta and compared the findings with 45 tumors from patients residing in low-pollution regions. Results: Rates of K-ras mutation in codon 12 and of p53 mutation in exons 5.8 were higher in tumors of patients from the high-pollution region as compared with the low-pollution regions (61.5 versus 34.2%, re- spectively, for K-ras, P = 0.01; 25.9 versus 11.6%, respectively, for p53, P = 0.08). There were also distinct differences in the specific types of K-ras and p53 mutations between the two regions. The ratio of G-to-T k-ras transversion mutation (codon 12) rela- tive to wild-type was significantly higher in tumors from the high- pollution region (0.90) than tumors from the non-pollution site ( 0.28 P = 0.03). Relative to tumors with wild-type, the ratio of p53 mutations in exons 5, 7 or 8 to wild-type in tumors from the high-pollution region was significantly higher than the ratio from the non-pollution site (0.28 versus 0.03, P = 0.01). Logistic re- gression showed that G-to-T transversion mutation in K-ras was predicted by the region of residence of the patients. Conclusions: Our study reveals that there are differences in the frequencies and types of K-ras and p53 mutations found in pancreatic adenocarcinomas of patients in high-pollution and low-pollution regions in Egypt and suggests that environmental factors may explain these differences. We speculate that gene.environment interactions in pancreatic carcinogenesis also occur in other populations.Name: Prof. Inas Ahmed El-Attar
Dept.: Epidemiology & BiostatisticsTitle: [18fdg] Pet-Ct-Based Intensity-Modulated RadiotherapyTreatment Planning of Head and Neck CancerMazen El-Bassiouni, I. Frank Ciernik, J. Bernard Davis, Inas El-Attar, Beatrice Reiner, Cyrill Burger, Gerhard W. Goerresand and Gabriela M. StuderJournal: Radiation Oncology Biol. PhysISSN: 0360-3016 Impact Factor: 4.556Abstract:Purpose: To define the best threshold for tumor volume delineation of the (18) fluoro-2-deoxyglucose positron emission tomography (18 FDG-PET ) signal for radiotherapy treatment planning of intensity-modulated radiotherapy (IMRT) in head and neck cancer. Methods and Materials: In 25 patients with head-and-neck cancer, CT-based gross tumor volume (GTVCT) was delineated. After PET-CT image fusion, window level (L) was adapted to best fit the GTVCT, and GTVPET was delineated. Tumor maximum (S) and background uptake (B) were measured, and the threshold of the background-subtracted tumor maximum uptake (THR) was used for PET signal segmentation. Gross tumor volumes were expanded to planning target volumes (PTVs) and analyzed. Results: The mean value of S was 40 kBq/mL, SIB ratio was 16, and THR was 26%. The THR correlated with S (r = -0.752), but no correlation between THR and the SIB ratio was seen (r = - 0.382). In 77% of cases, S was >30 kBq/mL, and in 23% it was ≤30 kBq/mL, with a mean THR of 21.4% and 41.6%, respectively (p < 0.001). Using PTVPET in radiotherapy treatment planning resulted in a reduced PTV in 72% of cases, while covering 88.2% of GTVCT, comparable to the percentage of GTVPET covered by PTV CT (P = 0.15). Conclusions: A case-specific PET signal threshold is optimal in PET-based radiotherapy treatment planning. Signal gating using a THR of 20% in tumors with S >30% ± 1.6% kBq/mL and 40% in tumors with S ≤ 30% ± 1.6% kBq/mL is suitable. Keywords:[18FDG] PET-CT fusion; PET segmentation; Head-and-neck cancer; Intensity modulation; Treatment planning.ISSN : 1743-422X Impact Factor : 1.94
Journal : Virology Prevalence of Transfusion Transmitted Virus (TTV) Genotypes Among HCC Patients in Qaluobia Governorate.Mohamed M Hafez , Sabry M Shaara y, Amr A Hassan, Rabab F Salim , Fatma M Abd El S and Amal E AliAbstract :Background: Transfusion Transmitted virus (TTV) is a novel single-stranded DNA virus that was identified in patients with post-transfusion hepatitis of non-A-G type. Clinical significance of TTV infection was analyzed in Egyptian hepatocellular carcinoma (HCC) patients. The present study attempted to clarify these issues in Egypt, particularly in Qaluobia governorate, a country known for its high endemicity of liver disease and hepatotropic viruses. Methods: TTV are determined in the serum of 60 samples obtained from HCC and liver cirrhosis (LC) patients and 30 healthy individuals. TTV DNA is amplified by nested-PCR with TTV-specific mixed primers derived from the conserved open reading frame 1 (ORF1) region followed by digestion with restriction enzyme. Using the enzymes HaeIII, DraI, EcoRI and PstI, we are able to distinguish between the four TTV genotypes. Results: The positive rate of TTV detection was
46.7%, 40% and 36.7% among HCC, LC patients and healthy individuals respectively. The more prevalence genotype was detected in the positive serum samples was genotype 1 (35.7%) in HCC patients, (50%) in LC and (63.3%) in healthy individuals, Genotype 5 (21.4%), (25.5%) and (18.2%) in HCC, LC and healthy individuals respectively. Discussion: This study indicates that TTV is commonly present in adult patients with HCC and LC as well as healthy individuals. The most prevalence TTV genotype is genotype 1. It seems that the infection neither contribute to the severity of liver disease no to the causation of HCC. Journal : Clinical Oncology
Symptoms and Patient-Reported Well-Being: Do They Predict Survival in Malignant Pleural Mesothelioma? A Prognostic Factor Analysis of EORTC-NCIC 08983: Randomized Phase III Study of Cisplatin With or Without Raltitrexed in Patients with Malignant Pleural MesotheliomaAndrew Bottomley, Corneel Coens, Fabio Efficace, Rabab Gaafar, Christian Manegold, Sjaak Burgers, Mark Vincent, Catherine Legrand and Jan P. van Meerbeeck Purpose: Malignant pleural mesothelioma (MPM) is a rare disease. Unlike other advanced cancer types, little is known about patient-reported symptoms or health-related quality of life (HRQOL) and their possible prognostic value. This study reports an evaluation of the prognostic value of these factors using data gathered from a recent randomized controlled trial. Patients and Methods:Patients were entered onto this trial if they had a histologically proven unresectable MPM, not pretreated with chemotherapy, WHO performance statusX2, and adequate hematologic, renal, and hepatic function. Patients were randomly assigned to receive cisplatin 80 mg/m2 intravenously on day 1, without or with preceding infusion of raltitrexed 3 mg/m2. HRQOL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30/Lung Cancer 13 tool. The Cox proportional hazards regression model was used for the univariate and multivariate analyses of survival, along with a bootstrap validation technique. Included were the EORTC prognostic index (PI) composed of stage of disease, histology type, time since diagnosis and WBC, and, in addition, 10 selected key symptoms and HRQOL scales. Results:Two hundred fifty patients were randomly assigned (80% male; median age, 58 years; WHO performance status 0, 1, 2 in 25%, 62%, and 13% of cases, respectively). Two hundred twenty-nine patients (91.6%) had a valid HRQOL assessment. The final multivariate model retained the PI, pain (P=.0001), and appetite loss (P<.0100) as independent prognostic indicators of survival. Conclusion:Results suggest that the PI, pain, and appetite loss may be independent prognostic factors in patients with advanced MPM.Dep. : Clinical PathologyName : Prof . Sohair Abdel Latif EissaISSN : 0008-2626 Impact Factor :Journal : General Virology Genetic Diversity in Hepatitis C Virus in Egypt and Possible Association With Hepatocellular CarcinomaGamal Esmat and Sohair A. EissaAbstract :Egypt has one of the world.s highest prevalences of hepatitis C virus (HCV) infection, with a majority of genotype 4 infections. To explore the genetic diversity of HCV in Egypt, sera from 131 Egyptians [56 from community studies, 37 chronic hepatitis patients, 28 hepatocellular carcinoma (HCC) patients and 10 patients with non Hodgkin.s lymphoma] were genotyped by restriction fragment-length polymorphism
and phylogenetic analyses of sequences from the mid-core and non-structural 5B regions. The different genotyping methods showed good agreement. The majority of the viruses (83 of 131; 63 %) were of subtype 4a, but five other subtypes within genotype 4 were also observed, as well as three genotype 1b, five genotype 1g and one genotype 3a samples. Interestingly, subtype 4o, which was easily identifiable in all three genomic regions, showed an association with HCC (P=0.017), which merits further investigation. ISSN : 013-3334 Impact Factor : 5.366Journal : Carcinogenesis Candidate Markers for the Detection of Hepatocellular Carcinoma in Low-Molecular Weight Fraction of SerumIman Gouda and Sohair A. EissaAbstract :Hepatocellular carcinoma (HCC) represents an important public health problem in Egypt where up to 90% of HCC cases are attributable to hepatitis C viral (HCV) infection. Serum alpha-fetoprotein is elevated in only -60% of HCC patients. The development of effective markers for the detection of HCC could have an impact on cancer mortality and significant public health implications worldwide. The objective of our study was to assess six candidate markers for detection of HCC identified by mass spectrometric analysis of enriched serum. The study examined 78 HCC cases and 72 age- and gender-matched cancer-free controls recruited from the Egyptian population. Matrix assisted laser desorption-ionization time-of-flight mass spectrometric analysis of enriched low molecular weight fraction of serum was used for identification of the candidate markers. Our analyses show that all six candidate markers are associated with HCC after adjustment for important covariates including HCV and hepatitis B viral infections. The marker candidates are independently predictive ofHCC with areas under the receiver operating characteristic (AuROC) curve ranging from 63-93%. A combination of the six markers improves prediction accuracy to 100% sensitivity, 91 % specificity and 98% AuROC curve in an independent test set of 50 patients. Two of the candidate markers were identified by sequencing as fragments of complement C3 and C4. In conclusion, a set of six peptides distinguished with high prediction accuracy HCC from controls in an Egyptian population with a high rate of chronic HCV infection. Further evaluation of these marker candidates for the diagnosis of HCC is needed.
2007September 2007- cancer NCIIs a Patient.s Self-Reported Health-Related Quality of Life A Prognostic Factor For Survival in Non-Small-Cell Lung Cancer Patients? A Multivariate Analysis of Prognostic Factors of EORTC Study 08975F. Efficace*, A. Bottomley, E. F. Smit, P. Lianes, C. Legrand, C. Debruyne, F.Schramel, H. J. Smit, R. Gaafar, B. Biesma, C. Manegold, C. Coens, G. Giaccone &J. Van MeerbeeckISSN : 0923-7534 Impact Factor: 4.319Journal: Annual of OncologyAbstractBackground: The aim of this prognostic factor analysis was to investigate if a patient.s selfreported health-related quality of life (HRQOL) provided independent prognostic information for survival in non-small cell lung cancer (NSCLC) patients. Patients and methods: Pretreatment HRQOL was measured in 391 advanced NSCLC patients using the EORTC QLQ-C30 and the EORTC Lung Cancer module (QLQ-LC13). The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap validation technique was used to assess the stability of the outcomes. Results: The final multivariate Cox regression model retained four parameters as independent prognostic factors for survival: male gender with a hazard ratio (HR) = 1.32 (95% CI 1.03.1.69; P = 0.03); performance status (0 to 1 versus 2) with HR = 1.63 (95% CI 1.04.2.54; P = 0.032); patient.s self-reported score of pain with HR= 1.11 (95% CI 1.07.1.16; P < 0.001) and dysphagia with HR = 1.12 (95% CI 1.04.1.21; P = 0.003). A 10-point shift worse in the scale measuring pain and dysphagia translated into an 11% and 12% increased in the likelihood of death respectively. A risk group categorization was also developed. Conclusion: The results suggest that patients. self-reported HRQOL provide independent prognostic information for survival. This finding supports the collection of such data in routine clinical practice.KeywordsLung cancer; Prognostic factor; Quality of life; Survival.
May 2009
Title : The in Vitro Promising Therapeutic Activity of Thymoquinone on Hepatocellular Carcinoma Cell Line. Authors: Wafaa A. Ahmed , Sohair A. Hassan, Fayek M. Galeb, Maha A. El-Taweel and Farid A. Abou-BedairPublished In : Global Veterinaria ISSN 1992 - 6197 Impact FactorAbstract :Black seed (Nigella sativa) is considered as a biological response modifiers (B R M). Thymoquinone (TQ) is the bioactive and the most abundant constituent of the volatile oil of this seed which, has been shown to possess an anti-inflammatory, antioxidant and antineoplastic effects. In this study, the effect of TQ on HepG2 cell line was investigated in an attempt to identify its potential mechanism of action. Cell viability and proliferation were assessed against different concentrations of TQ and revealed a remarkable inhibition of HepG2 cells in a dose dependant manner. TQ ability-induced apoptosis was determined by Flowcytometry and by colorimetric measurement of Caspases 3 and 9. The apoptotic effect of TQ was much more dramatic after 12 hrs of treatment and the activity level of Caspases 3 and 9 was increased. Also, Flowcytometric analysis of cell cycle revealed an early G1/S arrest of cells which is characteristic of apoptosis. It could be concluded that Thymoquinone is a promising anti-cancer therapeutic agent for hepatocellular carcinoma. Keywords:Black seed (Thymoquinone); Apoptosis; Cell cycle; Flowcytometry.The National Cancer Institute
Dep. : Cancer BiologyName : Wafaa Abdullah AhmedTitle : Influence of Ondansteron on the Antitumor Activity and Lung Toxicity of BleomycinAuthors: Ghada M.Suddek, Wafaa A. Ahmed, Hatem A. Salem, Osama A. Badary, Nariman M. Gameil and Hassan A.EL.kashPublished In : Journal of Basic and Applied ScienceISSN 1814 - 8085 Impact Factor 0.4Abstract :Bleomycin (BLM) is well known by its antitumor activity both in vitro and in vivo. However, pulmonary fibrosis has been considered the dose limiting toxicity of the drug. Moderate nausea and vomiting occur in virtually all patients taken BLM. Ondansetron (OND) is a highly selective 5-HT3 receptor antagonist with significant antiemetic activity. This study was conducted to investigate the effect of OND administration on the antitumor and lung toxicity of BLM. The antitumor activity was evaluated both in vitro and in vivo using Ehrlich ascites carcinoma (EAC) cells. Ondansetron did not alter the antitumor effect of BLM in vitro or in vivo. The lung toxicity of BLM was evidenced by decrease in the body weight, increase in the lung/body weight ratio, decrease in the response of pulmonary arterial rings to 5HT and increase in the contractility of tracheal smooth muscles induced by ACh. The toxicity was also confirmed
biochemically by marked increases in hydroxyproline and lipid peroxidation in rat lung and the decrease in GSH level. Pretreatment with ondansetron decreased lipid peroxidation and normalized GSH level and hence enhanced the percent survival of rats. The results of the present study indicate that OND did not modify the antitumor effect of BLM but ameliorated the increase in some biochemical, markers associated with BLM-induced lung toxicity. Keywords:Bleomycin (BLM); Ondansetron (OND); Ehrlich Ascites Carcinoma (EAC); Pulmonary fibrosis.The National Cancer InstituteDep. : Clinical OncologyName : Hatem A. AzimTitle : Systemic Nonhormonal Management of Advanced Prostate Cancer and ItsLikely Impact on Patients' Survival and Quality of Life [REVIEW]Authors: Hatem .A .Azim and Tony MokPublished In : Anti-Cancer DrugsISSN 0959 - 4973 Impact Factor 2.347Abstract :Prostate cancer is a hormonal sensitive disease with a response rate ranging from 80 to 90%; however, the majority of patients develop hormone resistance resulting in poor long term survival. Chemotherapy has demonstrated a benefit over steroids in improving the quality of life in the hormone refractory phase. Furthermore, the introduction of docetaxel succeeded in improving the survival of these patients in first-line therapy. Second-line treatment following docetaxel is challenging with no agent classified as standard in this setting. In the last 5 years, several drugs have shown promising results in initial evaluation. However, randomized phase III trials would be needed to answer this question. The majority of patients develop bone metastasis and the use of bisphosphonates has yielded encouraging results. Our understanding of the biology of hormone refractory prostate cancer has improved dramatically over the past few years and has translated into the developments of new therapeutic targets for this disease. Agents affecting several targets, including calcitriol, endotheline-1, bcl-2, and angiogenesis, are being studied currently and have the potential to change the treatment paradigms of this otherwise fatal disease. This review focuses on current and potential treatment options, including cytotoxic agents, bisphosphonates, and targeted agents, for patients with hormone refractory prostate cancer and the impact of these options on survival and quality of life.Keywords:Bisphosphonates; Estramustine; Hormone refractory prostate cancer; Targeted agents.The National Cancer Institute
Dep. : Clinical OncologyName : Hatem A. AzimTitle : Targeting Her-2/neu in Breast Cancer: As Easy as This!Authors: Hamdy Azim and Hatem A. AzimPublished In : OncologyISSN 0030 - 2414 Impact Factor 2.444Abstract :
Her-2/neu-positive tumors account for approximately 20% of all breast cancer and these tumors carry poor prognosis. Trastuzumab and lapatinib are 2 agents that have gained FDA approval for treating Her-2/neu-positive breast cancer. Trastuzumab has been shown to improve all endpoints when added to chemotherapy compared to chemotherapy alone, both in the adjuvant and metastatic phases. The addition of lapatinib to capecitabine has recently been shown to improve time to progression in rastuzumabrefractory patients with unique activity against brain metastasis. In spite of their impressive results, a significant fraction of patients still develop either primary or secondary resistance, a fact that entails the discussion of possible mechanisms of resistance. Biomarkers including PTEN, p95HER2, IGF1R and others have been linked to response to Her-2/neu-targeting agents. In this article, we overview the Her-2/neu signaling pathways and how a better understanding of the different molecular aspects of this oncogene could serve in optimizing the use of Her-2/neu-targeting agents. We also discuss the preclinical and clinical data of these biomarkers that may guide clinicians in choosing the right drug whenever possible.Keywords:Her-2/neu; Trastuzumab; Lapatinib; Truncated Her-2; PTEN; p27 kip; TopoisomeraseII; Resistance.The National Cancer Institute
Dep. : Radiation Oncology
Name : Samy A. El-BadawyTitle : Breast Cancer After Treatment Of Hodgkin's Lymphoma: General ReviewAuthors: Mohamed A. Alm El-Din, Samy A. El-Badawy and Alphonse G. TaghianPublished In : International J. of Radiation Oncology Biology PhysicsISSN 0360 - 3016 Impact Factor 4.29Abstract :The improved survival rates among patients with Hodgkin's lymphoma over the past few decades have come with increased incidence of second malignancies. One of the major concerns among female survivors is the significantly elevated risk of breast cancer that appears with extended follow-up. In this review, we include the published literature regarding the risk of breast cancer after irradiation for Hodgkin's lymphoma. We also present the possible long-term surveillance strategies and the optimal time to start screening these women. This could potentially help in early detection of secondary breast cancers and consequently improve outcomes. Furthermore, because of prior radiotherapy, the management of the breast cancer among this unique population has been controversial. We discuss the characteristics of breast cancer that occurs after Hodgkin's lymphoma 'and also treatment options that could be implemented. Keywords:Breast Cancer; Hodgkin's; Lymphoma review.The National Cancer Institute
Title : Prevalence and Pattern of Lymph Node Metastasis in Malignant Pleural MesotheliomaAuthors: Rabab M. Gaafar, Hoda A. Baki, Hesham M. El Hosieny, Fatma Aboulkasem, Eman G. Farahat, Akram M. Nouh, and Kamal A. MansourPublished In : Annals of Thoracic SurgeryISSN 0003 - 4975 Impact Factor 2.022Abstract :Background. The incidence and pattern of nodal metastases in mesothelioma are not well understood. This study was conducted to evaluate the prevalence andpattern ofnodal metastasis in mesothelioma patients. Methods. The study included 53 patients with mesothelioma.The first 37 patients (group I) underwent combinedmodality treatment without preoperative mediastinoscopy. The second group included 16 patients (groupII) with pretreatment mediastinoscopy. Results. A total of 18 patients had positive lymphnodes, 12 in group I and 6 in group II; of the latter, 4 hadpositive mediastinoscopy and 2 had positive nodes onfinal pathology. Postoperatively, a mean of 14 nodes weredissected (range, 5 to 34). In the post-pleuropneumonectomygroup, 6 of 14 patients had positive hilar nodemetastases in addition to positive mediastinal lymphnodes. One patient had positive hilar nodes only. Of the49 patients operated on, only 7 had no lung invasion bypathologic evaluation, and none had positive hilar nodes.The mechanism of spread of the disease to hilar nodesmay be through lung invasion and not due to directspread from the pleura. This observation raises thepossibility that mediastinal nodes should be consideredthe primary station in patients with mesothelioma,whereas hilar node metastasis necessitated lung invasion first.Conclusions. The pattern of nodal metastases may bedifferent from that of lungcancer, and multicenter studiesare needed to evaluate this observation.Keywords:Pattern; Lymph node; Metastasis; Mesothelioma.
OCT 2009
Oct., 2009Faculty of National Cancer InstituteDep. : Cancer BiologyName : Marwa Wagih Kamel BayommiTitle :Catecholestrogens induce oxidative stress and malignant transformation in human endometrial glandular cell: Protective effect of catechol-O-methyltransferse Authors: Salma A. Salma, Marwa Kamel , Mohamed-Hakim Ben Nasser, Ayman Al-Hendy, Shaleen Botting and Concepion ArrastiaPublished In : Int.J.Cancer:123, 1246-1254 (2008)ISSN 0020-7136 Impact Factor 4.555Abstract :Prolonged exposure to unopposed estrogen is a major risk factor for the development of endometrial cancer. Oxidative metabolism of estradiol (E2) into the catechol estrogen (CEs), 4-hydroxyestradiol (4-OHE2) and 2-hydroxyestradiol (2-OHE2), may play an important role in estrogen carcinogenicity. CEs can be oxidized to the corresponding ortho-quinone derivatives with concomitant formation of the reactive oxegen species (ROS). Catechol-O-methyltransferase (COMT) is the major enzyme involved in the detoxification of CEs in extrahepatic tissues. We investigated the potential of E2, 2-OHE2 and 4-OHE2 to induce microsatellite instability (MSI) and neoplastic transformation of immortalized human endometrial glandular (EM) cells. Keywords: Catecholestrogens; COMT; Genomic Instability; Endometrial Cancer.Faculty of National Cancer Institute
Dep. : Cancer BiologyName : Samia ShoumanTitle : Design, synthesisand in vitro antitumor activity of 4- aminoquinoline and 4- minoquinazolinederivativestargeting EGFR tyrosine kinase Authors : Khaled Abouzid and Samia ShoumanPublished In : Bioorsanic and Medicinal ChemistrvISSN 0968-0896 Impact Factor 2.662Abstract :Two series of new 6-alkoxy-4-substituted-aminoquinazolines (24f) and their ioisotericquinolinecongeners (5-7c) were designedand synthesized. Virtual screeningwas carried out through docking the designedcompounds into the ATP binding site of epidermalgrowth factor receptor (EGFR) to predict if thesecompoundshave analogousbinding mode to the EGFR inhibitors. The newly synthesizedcompoundswere testedin vitro on human breastcarcinomacell line (MCF-7) in which EGFR is highly expressed. Most of the testedcompoundsexploited potent antitumor activity with IC50 values in
the nanomolar rangein particular compound 3b which displayedthe highest activity amongthe testedcompoundswith IC50 equal to 0.13nmol.Keywords:Aminoquin azoli\e; Aminoquinoline; EGFR tyrosine kinase inhibitor; Antitumor active docking study.Faculty of National Cancer Institute
Dep. : Tumour BiologyName : Raafat Abd El-Gawad El-Gharib El-AwadyTitle : Apoptosis is the most efficient death-pathway in tumor cells after topoisomerase II inhibitionAuthors : Raafat A. El-Awady, Mahmoud M. Ali, Ekram M. Saleh and Fayek M. GhalebPublished In : Saudi MedicalISSN 0379- 5284 Impact Factor 0.3Abstract :Objective: To compare the efficiency of apoptosis and other modes of cell death in killing tumor cells after the induction of DNA damage by topoisomerase inhibitors like etoposide. Methods: This study was carried out in the Tumor Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt, from September 2005 to August 2007. The breast cancer MCF7, the cervix carcinoma, human cervical adenocarcinoma (Hela), and the brain tumor U251 cell lines were exposed to etoposide. Apoptosis was detected using the flow cytometry and the DNA ladder formation methods. Cell viability was determined by a colorimetric assay, and the residual DNA double-strand breaks (dsb) were measured by gel electrophoresis. Results: The Hela cells were the most, the MCF7’s were moderately, whereas the U251’s were the least sensitive to etoposide. Apoptosis was detected only in Hela cells whereas the other 2 cell lines showed a very low level of apoptosis (only 3% increase above the control cells). At equitoxic drug concentrations (namely IC50), the Hela cells showed the lowest amount of non-repaired DNA dsb, and the MCF7’s showed the highest amount, whereas the U251 cells showed a moderate amount. Conclusions: These results indicate that although other modes of cell death exist, apoptosis is the most efficient and requires lower drug concentrations and fewer numbers of non-repaired dsb to give the same killing effect. Clinically, this means that tumors that can execute apoptosis may require lower doses of topoisomerase inhibitors than those that lost the ability to exercise apoptosis.Keywords: Topoisomerase; DNA repair and apoptosis.Faculty of National Cancer Institute
Dep. : Tumour BiologyName : Raafat Abd El-Gawad El-Gharib El-AwadyTitle : -Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease and ionizing radiation-induced DNA double-strand breaksAuthors : Leonie Schulte-Uentrop, Raafat A. El-Awady, Lena Schliecker, Henning Willers and Jochen Dahm-DaphiPublished In : Nucleic Acids ResearchISSN 0305- 1048 Impact Factor 6.954Abstract :
Non-homologous end-joining (NHEJ) of DNA doublestrand breaks (DSBs) is mediated by two protein complexes comprising Ku80/Ku70/DNA-PKcs/ Artemis and XRCC4/LigaseIV/XLF. Loss of Ku or XRCC4/LigaseIV function compromises the rejoining of radiation-induced DSBs and leads to defective V(D)J recombination. In this study, we sought to define how XRCC4 and Ku80 affect NHEJ of sitedirected chromosomal DSBs in murine fibroblasts. We employed a recently developed reporter system based on the rejoining of I-SceI endonucleaseinduced DSBs. Wefound that the frequency of NHEJ was reduced by more than 20-fold in XRCC4_/_compared to XRCC4+/+ cells, while a Ku80 knock-out reduced the rejoiningefficiency by only 1.4-fold. In contrast, lack of either XRCC4 or Ku80 increased end degradation and shifted repair towards a mode that used longer terminal microhomologies for rejoining. However, both proteins proved to be essential for the repair of radiationinduced DSBs. The remarkably different phenotype of XRCC4-and Ku80-deficient cells with regard to the repair of enzyme-induced DSBs mirrorsthe embryonic lethality of XRCC4 knock-out mice as opposed to the viability of the Ku80 knock-out. Thus, I-SceI-induced breaks may resemble DSBs arising duringnormal DNA metabolism and mouse development. The removal of these breaks likely has different genetic requirements than the repair of radiation-induced DSBs.Keywords:XRCC4; Ku80; DSB repair; NHEJ.
