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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
advanced NSCLC. These results support further investigation of gefitinib in this disease setting.
Keywords
Docetaxel; 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 Study
ndrew Bottomley, Rabab Gaafar, Christian Manegold, Sjaak Burgers, Corneel Coens, Catherine Legrand,
Mark Vincent, Giuseppe Giaccone, and Jan Van
Meerbeeck
Abstract
Purpose: 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 firstline 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: 2.54
Journal: Journal of Viral Hepatitis 98 (2006)
Immunomodulators, sFas and Fas-L as potential noninvasive predictors
of IFN treatment in patients with HCV genotype-4
A. R. N. Zekri,1 H. A. Haleem,2 G. E. -D. Esmat,2 A. A. Bahnassy,3 H. M. A. ElDin,1
M. M. Hafez,1 A. F. Sharaby,2 H. Sharaf4 and M. S. E.-D. Zakaria2
Abstract
Recent 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.
Keywords
HCV, 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 treatment
A. A. Bahnassy, A-R N Zekri,1 N Asaad,2 S El-Houssini, H M Khalid,3 L M Sedky4 & N M Mokhtar
Abstract
Aims: 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 lymphoma 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 also
correlated 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 delLMP1 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 associated 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
MONEIM
Abstract
OBJECTIVE
To 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) and
1.9 (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.
Keywords
Urinary 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-Sedah
Abstract
Background 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 biopsy
Keywords
Invasive fungal infection IFI; Haemato-oncology patients; Polymerase ahain reaction PCR;
Galactomannan GM; Aspergillus antigen.
ISSN : 0743-684X Impact Factor : 0.55
Journal : 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. and
Mahmoud 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 flap
in midface reconstruction. Similar to other soft tissue flaps, additional skeletal reconstruction may still
be required to achieve an optimal functional and aesthetic result.
Abstract :
ISSN : 1078-1439 Impact Factor : 1.07
Journal : Urologic Oncology: Seminars and Original Investigations 24 13-20 (2006)
Long-term results of primary adenocarcinoma of the urinary bladder: A report on 192 patients
Mohamed S. Zaghloul, Akram Nouh , Mohamed Nazmy, Samy Ramzy,
Ashraf S. Zaghloul, Mohamed Abou Sedira and Ehab Khalil
Abstract :
Objectives: To evaluate the clinical presentation and treatment end results of primary adenocarcinoma
of the urinary bladder, and to determine the significant independent prognostic factors that determine
this outcome. Patients and Methods: Of 3659 patients who underwent cystectomy, 192 had
adenocarcinoma of the urinary bladder, with a relative frequency of 5.2%. Most of these patients
(68.2%) presented in late stages (P3P4). The incidence of pelvic lymph nodes involvement was 25.5%.
Mucinous adenocarcinoma was reported in 28 patients (14.6%), papillary in 20 (10.4%), signet ring in 14
(7.3%), while not otherwise specified was reported in 130 (67.7%) in the cystectomy specimens. Results:
Mucinous and signet-ring histologic subtypes showed increased frequency of high stages and high
grades, and more nodal involvement than the papillary and not otherwise specified. All patients were
treated with radical cystectomy and pelvic lymphadenectomy with (69 patients) or without (123)
postoperative radiotherapy. The 5-year disease-free survival rate was 46 4% for all patients with
adenocarcinoma. Postoperative radiotherapy improved the disease-free survival significantly. The 5-year
disease-free survival rate for the postoperative radiotherapy group was 616% compared to 375% for the
cystectomy alone group (P0.002). Local control rate was significantly improved from 537% for
cystectomy alone to 963% for postoperative radiotherapy patients (P0.00001). Distant metastases were
the leading cause of death in the postoperative radiotherapy group. Conclusions: Within the limitations
provided by retrospective studies, it could be concluded that postoperative radiotherapy improved the
disease-free survival through its effect on local control. The disease-free survival independent
prognostic variables were tumor stage, postoperative radiotherapy, nodal involvement, and
adenocarcinoma subclassification. These factors, except the adeno-subclassification, were also found to
determine the local control rate. On the other hand, the independent prognostic factors for distant
metastasis were lymph nodal involvement, stage, and adeno-subclassification.© 2006 Elsevier Inc. All
rights reserv.
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 Mesothelioma
Abdel-Rahman N. Zekri, Abeer A. Bahnassy, Waleed S. Mohamed, Nelly assan,Abdel-Rahman M. AbdelRahman, Fatma Abou El-Kassem and Rabab Gaafar
Abstract :
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 correlation 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.
Keywords
Asbestos; Malignant Pleural Mesotheliom; P53; Rb; Sv40
Dept.: Tumor Biology
Title : Androgen Profiles Among Egyptian Adults Considering Liver
Status
Cristina E Aguilar, Amr S Soliman, Daniel S McConnell, Abdel-Rahman Zekri, Mousumi Banerjee, Ayman
Omar, Mohamed Sharawy, Sherif Omar, Ahmed Raouf and MaryFran R Sowers
Journal: Gastroenterology and Hepatology
ISSN: 0815-9319 Impact Factor: 1.785
Abstract:
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 Infection
Abdel-Rahman N Zekri, Mohamed M Hafez, Nahed I Mohamed, Zeinab K
Hassan, Manal H El-Sayed, Mohsen M Khaled and Tarek Mansour
Abstract :
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 Malignancies
Abdel-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 nonHodgkin.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-4
Abdel-Rahman Zekri, Waleed Mohamed, Abeer A. Bahnassy, Lobna Refat, Mohsen Khaled, Sameh
Shalaby and Mohamed Hafez
Abstract :
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 HCVRNA 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 Carcinoma
Abeer A. Bahnassy, Abdel Rahman N Zekri, Maha Saleh, Mohammad Lotayef, Manar Moneir and Osama
Shawki
Abstract :
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 ElHaddad Nabil Ahmed
Journal: Pediatr Hematol Oncol
ISSN: 0888-0078 Impact Factor: 0.529
Abstract:
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 (IL8), 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 Study
Nabil 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-totreat 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.
Keywords : Delayed categorization; Discharge; Fever; Hospitalization; Neutropenia; Pediatric.
Dep. : Oncology
Name : Prof . Hussein Mostafa Khaled
ISSN : 0885-3177 Impact Factor : 2.121
Journal : Pancreas Lifestyle, Occupational, and Reproductive Factors in Relation
to Pancreatic Cancer Risk
An-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. Abbruzzese
Abstract :
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.
Dep. : Oncology
Name : Prof . Hussein Mostafa Khaled
ISSN : 0167-6806 Impact Factor : 4.671
Journal : Breast Cancer Research Treatment Molecular epidemiologic features of inflammatory breast
cancer: A Comparison Between Egyptian and US Patients
An-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. Soliman
Abstract :
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 : Carcinogenesis
Differences in K-ras and p53 Gene Mutations Among Pancreatic Adenocarcinomas Associated with
Regional Environmental pollution
Amr 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.Hamilton
Abstract :
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 highpollution 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 & Biostatistics
Title: [18fdg] Pet-Ct-Based Intensity-Modulated RadiotherapyTreatment Planning of Head and Neck
Cancer
Mazen El-Bassiouni, I. Frank Ciernik, J. Bernard Davis, Inas El-Attar, Beatrice Reiner, Cyrill Burger,
Gerhard W. Goerresand and Gabriela M. Studer
Journal: Radiation Oncology Biol. Phys
ISSN: 0360-3016 Impact Factor: 4.556
Abstract:
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 intensitymodulated 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 backgroundsubtracted 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 casespecific 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 Ali
Abstract :
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 Mesothelioma
Andrew 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 Pathology
Name : Prof . Sohair Abdel Latif Eissa
ISSN : 0008-2626 Impact Factor :
Journal : General Virology Genetic Diversity in Hepatitis C Virus in Egypt and Possible Association With
Hepatocellular Carcinoma
Gamal Esmat and Sohair A. Eissa
Abstract :
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 : 5.366
Journal : Carcinogenesis Candidate Markers for the Detection of Hepatocellular
Carcinoma in Low-Molecular Weight Fraction of Serum
Iman Gouda and Sohair A. Eissa
Abstract :
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 gendermatched cancer-free controls recruited from the Egyptian population. Matrix assisted laser desorptionionization 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.
2007
September 2007- cancer NCI
Is a Patient.s Self-Reported Health-Related Quality of Life A Prognostic Factor For Survival in NonSmall-Cell Lung Cancer Patients? A Multivariate Analysis of Prognostic Factors of EORTC Study 08975
F. 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 Meerbeeck
ISSN : 0923-7534 Impact Factor: 4.319
Journal: Annual of Oncology
Abstract
Background: 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 nonsmall 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 (QLQLC13). 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.
Keywords
Lung 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. AbouBedair
Published In : Global Veterinaria
ISSN 1992 - 6197 Impact Factor
Abstract :
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 Biology
Name : Wafaa Abdullah Ahmed
Title : Influence of Ondansteron on the Antitumor Activity and Lung Toxicity of Bleomycin
Authors: Ghada M.Suddek, Wafaa A. Ahmed, Hatem A. Salem, Osama A. Badary, Nariman M. Gameil
and Hassan A.EL.kash
Published In : Journal of Basic and Applied Science
ISSN 1814 - 8085 Impact Factor 0.4
Abstract :
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 Institute
Dep. : Clinical Oncology
Name : Hatem A. Azim
Title : Systemic Nonhormonal Management of Advanced Prostate Cancer and Its
Likely Impact on Patients' Survival and Quality of Life [REVIEW]
Authors: Hatem .A .Azim and Tony Mok
Published In : Anti-Cancer Drugs
ISSN 0959 - 4973 Impact Factor 2.347
Abstract :
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 Oncology
Name : Hatem A. Azim
Title : Targeting Her-2/neu in Breast Cancer: As Easy as This!
Authors: Hamdy Azim and Hatem A. Azim
Published In : Oncology
ISSN 0030 - 2414 Impact Factor 2.444
Abstract :
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 Her2/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; Topoisomerase
The National Cancer Institute
Dep. : Radiation Oncology
Name : Samy A. El-Badawy
Title : Breast Cancer After Treatment Of Hodgkin's Lymphoma: General Review
Authors: Mohamed A. Alm El-Din, Samy A. El-Badawy and Alphonse G. Taghian
Published In : International J. of Radiation Oncology Biology Physics
ISSN 0360 - 3016 Impact Factor 4.29
Abstract :
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
Dep. : Surgical Oncology
Name : Abdel Rahman Mohamed Abdel Rahman
Title : Prevalence and Pattern of Lymph Node Metastasis in Malignant Pleural Mesothelioma
Authors: Rabab M. Gaafar, Hoda A. Baki, Hesham M. El Hosieny, Fatma Aboulkasem, Eman G. Farahat,
Akram M. Nouh, and Kamal A. Mansour
Published In : Annals of Thoracic Surgery
ISSN 0003 - 4975 Impact Factor 2.022
Abstract :
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 lung
cancer, and multicenter studiesare needed to evaluate this observation.
Keywords:Pattern; Lymph node; Metastasis; Mesothelioma.
OCT 2009
Oct., 2009
Faculty of National Cancer Institute
Dep. : Cancer Biology
Name : Marwa Wagih Kamel Bayommi
Title :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 Arrastia
Published In : Int.J.Cancer:123, 1246-1254 (2008)
ISSN 0020-7136 Impact Factor 4.555
Abstract :
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 (4OHE2) 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 Biology
Name : Samia Shouman
Title : Design, synthesisand in vitro antitumor activity of 4- aminoquinoline and 4minoquinazolinederivativestargeting EGFR tyrosine kinase
Authors : Khaled Abouzid and Samia Shouman
Published In : Bioorsanic and Medicinal Chemistrv
ISSN 0968-0896 Impact Factor 2.662
Abstract :
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 Biology
Name : Raafat Abd El-Gawad El-Gharib El-Awady
Title : Apoptosis is the most efficient death-pathway in tumor cells after topoisomerase II inhibition
Authors : Raafat A. El-Awady, Mahmoud M. Ali, Ekram M. Saleh and Fayek M. Ghaleb
Published In : Saudi Medical
ISSN 0379- 5284 Impact Factor 0.3
Abstract :
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 Biology
Name : Raafat Abd El-Gawad El-Gharib El-Awady
Title : -Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease and ionizing
radiation-induced DNA double-strand breaks
Authors : Leonie Schulte-Uentrop, Raafat A. El-Awady, Lena Schliecker, Henning Willers and Jochen
Dahm-Daphi
Published In : Nucleic Acids Research
ISSN 0305- 1048 Impact Factor 6.954
Abstract :
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 knockout. 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.