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2011
Nouh, M. A. a, M. M. b Mohamed, M. c El-Shinawi, M. A. d Shaalan, D. e f Cavallo-Medved, H. M. g Khaled, and B. F. e h Sloane, "Cathepsin b: A potential prognostic marker for inflammatory breast cancer", Journal of Translational Medicine, vol. 9, 2011. AbstractWebsite

Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; however, very little is known about its role in IBC.Methods: In this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the levels of expression of CTSB in IBC versus non-IBC patient tissues. Previously, we found that CTSB is localized to caveolar membrane microdomains in cancer cell lines including IBC, and therefore, we also examined the expression of caveolin-1 (cav-1), a structural protein of caveolae in IBC versus non-IBC tissues. In addition, we tested the correlation between the expression of CTSB and cav-1 and the number of positive metastatic lymph nodes in both patient groups.Results: Our results revealed that CTSB and cav-1 were overexpressed in IBC as compared to non-IBC tissues. Moreover, there was a significant positive correlation between the expression of CTSB and the number of positive metastatic lymph nodes in IBC.Conclusions: CTSB may initiate proteolytic pathways crucial for IBC invasion. Thus, our data demonstrate that CTSB may be a potential prognostic marker for lymph node metastasis in IBC. © 2011 Nouh et al; licensee BioMed Central Ltd.

b Soubeyran, P. a, H. c Khaled, M. d MacKenzie, M. e Debois, C. e Fortpied, R. f de Bock, J. g Ceccaldi, D. h de Jong, H. a Eghbali, M. b i Rainfray, et al., "Diffuse large B-cell and peripheral T-cell non-Hodgkin's lymphoma in the frail elderly. A phase II EORTC trial with a progressive and cautious treatment emphasizing geriatric assessment", Journal of Geriatric Oncology, vol. 2, no. 1, pp. 36-44, 2011. AbstractWebsite

Objectives: Many frail elderly patients with diffuse large B-cell lymphoma (DLBCL) cannot tolerate standard chemotherapy treatment. The objective of this phase II trial was to assess the efficacy of a cautious COP-based (cyclophosphamide, vincristine, prednisone) regimen with comprehensive geriatric assessment (CGA). Trial registration number: NCT00039351. Materials and methods: DLBCL patients aged ≥70years with poor physiological functioning received cyclophosphamide (750mg/m2 IV at d1), vincristine (1.4mg/m2 IV at d1, maximum of 2mg) and prednisone (40mg/m2 d1 to d5) for six cycles. Comprehensive Geriatric Assessment (CGA) was performed for all patients before and after treatment. Results: Thirty-two patients were included, of whom 27 were evaluable for efficacy. Low response rates were observed with only 18.5% complete response and 25.9% partial response leading to the early termination of the trial. Despite strict dose reduction rules, high toxicity rates were observed with four severe toxicities and eight early deaths. CGA data showed that over 90% of patients were depressed, over 80% dependent for instrumental activities of daily living (IADL) and almost half of our patients had severe comorbidities showing that we clearly selected a population of "frail" elderly. Conclusion: This adapted COP regimen for vulnerable patients produced an 18.5% complete response rate. Future research will include the addition of rituximab to determine if it can improve treatment efficacy. The geriatric assessment should be part of routine management of frail patients with aggressive lymphomas as it allows us to identify specific issues of vulnerability in this population on which intervention should be focused. © 2010 Elsevier Inc.

Hamed, M. A. A. a, S. A. A. a Ahmed, and H. M. b Khaled, "Efficiency of diagnostic biomarkers among colonic schistosomiasis egyptian patients", Memorias do Instituto Oswaldo Cruz, vol. 106, no. 3, pp. 322-329, 2011. AbstractWebsite

The schistosomal parasite plays a critical role in the development of malignant lesions in different organs. The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for disease detection. The objective of this paper is to evaluate certain biochemical parameters as diagnostic tools to efficiently differentiate between colonic carcinoma and colonic carcinoma associated with schistosomal infection among Egyptian patients. The parameters under investigation are interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α), carcinoembryonic antigen (CEA) levels, tissue telomerase, pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and lactate dehydrogenase (LDH) enzyme activities. The results revealed a significant elevation in the level of the tumour markers IL-2, TNF-α and CEA as well as the activities of LDH, telomerase and G-6-PD among non-bilharzial and bilharzial colonic cancer groups, with a more potent effect in bilharzial infection-associated colonic cancer. A significant inhibition in PK activity was recorded in the same manner as compared to normal tissues. The efficacy of this biomarker was also evaluated through detecting sensitivity, specificity, negative and positive predictive values. In conclusion, schistosomal colonic carcinoma patients displayed more drastic changes in all parameters under investigation. The combination of the selected parameters succeeded in serving as biomarkers to differentiate between the two malignant types.

Aurer, I. a, H. b Eghbali, J. c Raemaekers, H. M. d Khaled, C. e Fortpied, L. e Baila, and R. W. c Van Der Maazen, "Gem-(R)CHOP versus (R)CHOP: A randomized phase II study of gemcitabine combined with (R)CHOP in untreated aggressive non-Hodgkin's lymphoma - EORTC lymphoma group protocol 20021 (EudraCT number 2004-004635-54)", European Journal of Haematology, vol. 86, no. 2, pp. 111-116, 2011. AbstractWebsite

Background: Despite recent improvements, many patients with aggressive non-Hodgkin's lymphoma (NHL) ultimately succumb to their disease. Therefore, improvements in front-line chemotherapy of aggressive NHL are needed. Gemcitabine is active in lymphoma.Methods: We performed a randomized phase II trial of the addition of gemcitabine to standard CHOP chemotherapy with or without rituximab [(R)CHOP]. The trial was also designed to determine the maximal tolerated dose (MTD) of gemcitabine in this combination. Patients with previously untreated aggressive NHL were randomized to receive either eight cycles of (R)CHOP given every 3 wk or (R)CHOP combined with gemcitabine [Gem-(R)CHOP].Results: Twenty-five patients were enrolled in the trial before early closure. Twelve were randomized to Gem-(R)CHOP and 13 to (R)CHOP. MTD of gemcitabine was 800 mg/m2 given on days 1 and 8; dose-limiting toxicity was hematologic. Five patients (42%) treated with Gem-(R)CHOP achieved complete response in comparison with 10 (77%) treated with (R)CHOP. Median time to treatment failure was 1.5 yr for Gem-(R)CHOP and 3.1 yr for (R)CHOP. Three patients receiving Gem-(R)CHOP had serious pulmonary toxicity, when compared to none receiving (R)CHOP. One patient died of pneumonitis.Conclusions: In this group of patients, addition of gemcitabine did not seem to improve outcomes. Gem-(R)CHOP in previously untreated patients with aggressive NHL occasionally results in severe, potentially fatal, pulmonary toxicity. © 2010 John Wiley & Sons A/S.

Goerlitz, D. a, M. b El Daly, M. b e Abdel-Hamid, D. A. c Saleh, L. a Goldman, S. b El Kafrawy, T. f Hifnawy, S. g Ezzat, M. A. h Abdel-Aziz, M. S. d Zaghloul, et al., "GSTM1, GSTT1 null variants, and GPX1 single nucleotide polymorphism are not associated with bladder cancer risk in Egypt", Cancer Epidemiology Biomarkers and Prevention, vol. 20, no. 7, pp. 1552-1554, 2011. AbstractWebsite

Background: Bladder cancer is the most common male malignancy in Egypt, consists predominantly of urothelial cell carcinoma (UCC) and squamous cell carcinoma (SCC), and disparities in incidence exist between men and women regardless of geographic region. Tobacco smoke exposure and Schistosoma haematobium (SH) infection and the presence of GSTM1, GSTT1, and GPX1 genotypes, as modulators of the carcinogenic effect of reactive oxidative species, were hypothesized to modify bladder cancer risk and possibly explain these gender differences. Methods: We evaluated the association between bladder cancer risk and functional polymorphisms in the GSTM1, GSTT1, and GPX1 genes in 625 cases and 626 matched population-based controls in Egypt and assessed for potential interactions between these candidate genes and environmental exposures, such as smoking and SH infection. We analyzed the risk for developing UCC and SCC separately. Results: None of these functional polymorphisms were significantly associated with bladder cancer risk. There were no significant interactions between genotypes and smoking or SH infection in this population, nor was any difference detected in genotypic risk between men and women. Conclusions: Our findings suggest that common genetic variations in GSTM1, GSTT1, and GPX1 are not associated with bladder cancer risk overall and that well-known environmental risk factors, such as smoking and SH infection, do not interact with these genes to modulate the risk. Impact: Our data indicate that common genetic variations in GSTM1, GSTT1, and GPX1 were not associated with bladder cancer risk. ©2011 AACR.

Soliman, A. S. a, C. G. b Kleer, K. c Mrad, M. d Karkouri, S. e Omar, H. M. e Khaled, A. - L. f Benider, F. B. g Ayed, S. S. e Eissa, M. S. a Eissa, et al., "Inflammatory breast cancer in North Africa: Comparison of clinical and molecular epidemiologic characteristics of patients from Egypt, Tunisia, and Morocco", Breast Disease, vol. 33, no. 4, pp. 159-169, 2011. AbstractWebsite

Understanding molecular characteristics that distinguish inflammatory breast cancer (IBC) from non-IBC is crucial for elucidating breast cancer etiology and management. We included 3 sets of patients from Egypt (48 IBC and 64 non-IBC), Tunisia (24 IBC and 40 non-IBC), and Morocco (42 IBC and 41 non-IBC). Egyptian IBC patients had the highest combined erythema, edema, peau d'orange, and metastasis among the 3 IBC groups. Egyptian IBC tumors had the highest RhoC expression than Tunisians and Moroccan IBCs (87% vs. 50%, vs. 38.1, for the 3 countries, respectively). Tumor emboli were more frequent in Egyptian IBC than non-IBC (Mean ± SD: 14.1 ± 14.0 vs. 7.0 ± 12.9, respectively) (P < 0.001) and Tunisians (Mean ± SD: 3.4 ± 2.5 vs. 1.9 ± 2.0, respectively) (P < 0.01). There was no difference of emboli in Moroccan tumors (1.7 ± 1.2 vs. 1.8 ± 1.2 for IBC and non-IBC, respectively (P=0.66). This study illustrates that RhoC overexpression and tumor emboli are more frequent in IBC relative to non-IBC from Egypt and Tunisia. Tumors of Moroccans were significantly different from Egyptian and Tunisian tumors for RhoC expression and emboli. Future studies should focus on relating epidemiologic factors and clinical pictures to molecular features of IBC in these and other populations. © 2012-IOS Press and the authors. All rights reserved.

Soliman, A. S. a, C. G. b Kleer, K. c Mrad, M. d Karkouri, S. e Omar, H. M. e Khaled, A. - L. f Benider, F. B. g Ayed, S. S. e Eissa, M. S. a Eissa, et al., "Inflammatory breast cancer in North Africa: Comparison of clinical and molecular epidemiologic characteristics of patients from Egypt, Tunisia, and Morocco", Breast Disease, vol. 33, no. 4, pp. 159-169, 2011. AbstractWebsite

Understanding molecular characteristics that distinguish inflammatory breast cancer (IBC) from non-IBC is crucial for elucidating breast cancer etiology and management. We included 3 sets of patients from Egypt (48 IBC and 64 non-IBC), Tunisia (24 IBC and 40 non-IBC), and Morocco (42 IBC and 41 non-IBC). Egyptian IBC patients had the highest combined erythema, edema, peau d'orange, and metastasis among the 3 IBC groups. Egyptian IBC tumors had the highest RhoC expression than Tunisians and Moroccan IBCs (87% vs. 50%, vs. 38.1, for the 3 countries, respectively). Tumor emboli were more frequent in Egyptian IBC than non-IBC (Mean ± SD: 14.1 ± 14.0 vs. 7.0 ± 12.9, respectively) (P < 0.001) and Tunisians (Mean ± SD: 3.4 ± 2.5 vs. 1.9 ± 2.0, respectively) (P < 0.01). There was no difference of emboli in Moroccan tumors (1.7 ± 1.2 vs. 1.8 ± 1.2 for IBC and non-IBC, respectively (P=0.66). This study illustrates that RhoC overexpression and tumor emboli are more frequent in IBC relative to non-IBC from Egypt and Tunisia. Tumors of Moroccans were significantly different from Egyptian and Tunisian tumors for RhoC expression and emboli. Future studies should focus on relating epidemiologic factors and clinical pictures to molecular features of IBC in these and other populations. © 2012-IOS Press and the authors. All rights reserved.

Metwally, N. S. a, S. A. a Ali, A. M. a Mohamed, H. M. b Khaled, and S. A. a Ahmed, "Levels of certain tumor markers as differential factors between bilharzial and non-biharzial bladder cancer among Egyptian patients", Cancer Cell International, vol. 11, 2011. AbstractWebsite

Background/Objective: Bladder cancer is the commonest type of malignant tumors as a result of schistosomaisis which is a major healthy problem in many subtropical developing countries. The aim of this study is to comparatively elucidate the underlying biochemical tumor markers in schistosomal bladder cancer versus non-schistosomal bladder cancer when compared to normal healthy ones.Methods: This work was performed on tissue specimens from total 25 patients and serum samples from total 30 patients versus ten healthy individuals served as control. The investigated parameters in serum are: xanthine oxidase (XO), fructosamine, lactate dehydrogense (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total proteins, essential and non- essential amino acids profile, hydroxyproline, total immunoglobulin E (IgE) and tumor necrosis factor alpha (TNF-α). In addition, the current investigation also extended to study some markers in tumor bladder tissues including, pyruvate kinase enzyme (PK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT).Results: Results showed that biharzial bladder cancer patients recored more significant elevation in serum XO, fructosamine, LDH, AST, ALT, hydroxyproline, IgE and TNF-α than in bladder cancer patients when compared to control ones. While, in tissues there were significant increase in PK, LDH, AST & ALT activities of schistosomal bladder cancer than in bladder cancer as compared to control healthy patients.Conclusions: It could be concluded that, bilharzial and non-bilharzial bladder cancer showed distinct biochemical profile of tumor development and progression which can be taken into consideration in diagnosis of bladder cancer. © 2011 Metwally et al; licensee BioMed Central Ltd.

Anderson, B. O. a, E. b Cazap, N. S. c El Saghir, C. - H. d Yip, H. M. e Khaled, I. V. f Otero, C. A. g Adebamowo, R. A. h Badwe, and J. B. f Harford, "Optimisation of breast cancer management in low-resource and middle-resource countries: Executive summary of the Breast Health Global Initiative consensus, 2010", The Lancet Oncology, vol. 12, no. 4, pp. 387-398, 2011. AbstractWebsite

The purpose of the Breast Health Global Initiative (BHGI) 2010 summit was to provide a consensus analysis of breast cancer control issues and implementation strategies for low-income and middle-income countries (LMCs), where advanced stages at presentation and poor diagnostic and treatment capacities contribute to lower breast cancer survival rates than in high-income countries. Health system and patient-related barriers were identified that create common clinical scenarios in which women do not present for diagnosis until their cancer has progressed to locally advanced or metastatic stages. As countries progress to higher economic status, the rate of late presentation is expected to decrease, and diagnostic and treatment resources are expected to improve. Health-care systems in LMCs share many challenges including national or regional data collection, programme infrastructure and capacity (including appropriate equipment and drug acquisitions, and professional training and accreditation), the need for qualitative and quantitative research to support decision making, and strategies to improve patient access and compliance as well as public, health-care professional, and policy-maker awareness that breast cancer is a cost-effective, treatable disease. The biggest challenges identified for low-income countries were little community awareness that breast cancer is treatable, inadequate advanced pathology services for diagnosis and staging, and fragmented treatment options, especially for the administration of radiotherapy and the full range of systemic treatments. The biggest challenges identified for middle-resource countries were the establishment and maintenance of data registries, the coordination of multidisciplinary centres of excellence with broad outreach programmes to provide community access to cancer diagnosis and treatment, and the resource-appropriate prioritisation of breast cancer control programmes within the framework of existing, functional health-care systems. © 2011 Elsevier Ltd.

Spencer, B. a, M. b Banerjee, S. c Omar, H. c Khaled, N. c Anwar, M. S. c Zaghloul, S. c Eissa, C. G. d Kleer, S. e Dey, S. D. d Merajver, et al., "Survival of inflammatory breast cancer patients compared to non-inflammatory breast cancer patients in egypt", Breast Journal, vol. 17, no. 5, pp. 545-547, 2011. AbstractWebsite
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2010
Lo, A. - C., A. S. Soliman, H. M. Khaled, A. Aboelyazid, and J. K. Greenson, "Lifestyle, occupational, and reproductive factors and risk of colorectal cancer.", Diseases of the colon and rectum, vol. 53, issue 5, pp. 830-7, 2010 May. Abstract

PURPOSE: Lifestyle factors and environmental exposures might help explain the risk of colorectal carcinoma in countries where the incidence is low, but unique patterns of young onset and a high proportion of rectal cancer exist.

METHODS: We obtained detailed lifestyle information from 421 patients with colorectal cancer and 439 hospital-controls in Egypt. Logistic regression models were computed to evaluate the risk factors of colorectal carcinoma.

RESULTS: A history of pesticide exposure and more frequently eating food directly from farms were significantly associated with a higher risk of colorectal carcinoma (odds ratio = 2.6; 95% CI = 1.1-5.9, and odds ratio = 4.6; 95% CI = 1.5-14.6, respectively). Parous women who reported 7 or more live births or breastfed for 19 months or longer per live birth had a significantly lower risk for colorectal carcinoma (odds ratio = 0.3; 95% CI = 0.2-0.7, and odds ratio = 0.2; 95% CI = 0.1-0.4, respectively). Compared with patients aged 40 years or older, industrial exposures were more common in younger patients (P = .05).

CONCLUSIONS: Agricultural and industrial exposures were associated with increased risk of colorectal carcinoma, whereas prolonged lactation and increased parity were inversely associated with colorectal carcinoma in women. Further research to elucidate the biological role of intense environmental and industrial exposures and reproductive factors including lactation may further clarify the etiology of colorectal cancer.

Maghraby, A. S., N. Shalaby, H. I. Abd-Alla, S. A. Ahmed, H. M. Khaled, and M. M. Bahgat, "Immunostimulatory effects of extract of Pulicaria crispa before and after Schistosoma mansoni infection.", Acta poloniae pharmaceutica, vol. 67, issue 1, pp. 75-9, 2010 Jan-Feb. Abstract

The immunostimulatory effects of methanolic extract from Pulicaria crispa were investigated in mice before and after infection with Schistosoma mansoni. Mice were subjected for daily intra-peritoneal injection by the extract (33 ng/mouse) for 10 successive days followed by infecting every mouse with 100 S. mansoni cercariae. Treatment with the extract induced significant increase (p < 0.05) in sera-IL-2 before and after infection. Upon using soluble worm antigen preparation or cancer bladder homogenates as antigens in ELISA, the detected levels of IgG were significantly (p < 0.05) higher in sera from treated-infected mice than untreated P. crispa infected mice. Using crude Escherichia coli lysate as an antigen in ELISA, it was detected a significant (p < 0.05) increase in IgG levels in sera from the extract-treated mice before and after infection.

Khaled, H. M., "Acknowledgment of Referees", Journal of Advanced Research, vol. 1, no. 4, pp. I-II, 2010. AbstractWebsite
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Wolpert, B. J. a, S. a Amr, S. b Ezzat, D. c Saleh, I. d Gouda, I. d Loay, T. h Hifnawy, N. N. e Mikhail, M. f Abdel-Hamid, M. a Zhan, et al., "Estrogen exposure and bladder cancer risk in Egyptian women", Maturitas, vol. 67, no. 4, pp. 353-357, 2010. AbstractWebsite

Objective: To examine associations between reproductive history and urinary bladder cancer in Egyptian women. Methods: We used questionnaire data from an ongoing, multicenter case-control study in Egypt. Controls were matched on age and residence area. This analysis focused on female cases with confirmed urothelial (UC) and squamous cell (SCC) carcinoma of the bladder. Results: We recruited 779 women (540 controls, 239 cases; >98.0% nonsmokers). Younger age at menopause (<45 y) and older age at first pregnancy (>18 y) were factors significantly associated with increased risk of bladder cancer, even after adjusting for schistosomiasis history and other covariates in the multivariable logistic model; adjusted odds ratio and 95% confidence intervals were 1.98 (1.41, 2.77) and 6.26 (3.46, 11.34), respectively. On the other hand, multiple pregnancies or use of oral contraceptives were associated with decreased odds of having bladder cancer. Similar associations were observed with UC and SCC when analyzed separately; however, the magnitude of association with SCC was lower than with UC. Conclusion: Our data suggest that early estrogen exposure, or the relative lack of it, plays a role in urinary bladder carcinoma development among Egyptian women. © 2010 Elsevier Ireland Ltd. All rights reserved.

b Maghraby, A. S. a, N. c Shalaby, H. I. c Abd-Alla, S. A. a Ahmed, H. M. d Khaled, and M. M. a b Bahgat, "Immunostimulatory effects of extract of Pulicaria crispa before and after Schistosoma mansoni infection", Acta Poloniae Pharmaceutica - Drug Research, vol. 67, no. 1, pp. 75-79, 2010. AbstractWebsite

The immunostimulatory effects of methanolic extract from Pulicaria crispa were investigated in mice before and after infection with Schistosoma mansoni. Mice were subjected for daily intra-peritoneal injection by the extract (33 ng/mouse) for 10 successive days followed by infecting every mouse with 100 S. mansoni cercariae. Treatment with the extract induced significant increase (p < 0.05) in sera-IL-2 before and after infection. Upon using soluble worm antigen preparation or cancer bladder homogenates as antigens in ELISA, the detected levels of IgG were significantly (p < 0.05) higher in sera from treated-infected mice than untreated P. crispa infected mice. Using crude Escherichia coli lysate as an antigen in ELISA, it was detected a significant (p < 0.05) increase in IgG levels in sera from the extract-treated mice before and after infection.

b Maghraby, A. S. a, N. c Shalaby, H. I. c Abd-Alla, S. A. a Ahmed, H. M. d Khaled, and M. M. a b Bahgat, "Immunostimulatory effects of extract of Pulicaria crispa before and after Schistosoma mansoni infection", Acta Poloniae Pharmaceutica - Drug Research, vol. 67, no. 1, pp. 75-79, 2010. AbstractWebsite

The immunostimulatory effects of methanolic extract from Pulicaria crispa were investigated in mice before and after infection with Schistosoma mansoni. Mice were subjected for daily intra-peritoneal injection by the extract (33 ng/mouse) for 10 successive days followed by infecting every mouse with 100 S. mansoni cercariae. Treatment with the extract induced significant increase (p < 0.05) in sera-IL-2 before and after infection. Upon using soluble worm antigen preparation or cancer bladder homogenates as antigens in ELISA, the detected levels of IgG were significantly (p < 0.05) higher in sera from treated-infected mice than untreated P. crispa infected mice. Using crude Escherichia coli lysate as an antigen in ELISA, it was detected a significant (p < 0.05) increase in IgG levels in sera from the extract-treated mice before and after infection.

Lo, A. - C. a, A. S. a Soliman, H. M. b Khaled, A. c Aboelyazid, and J. K. d Greenson, "Lifestyle, occupational, and reproductive factors and risk of colorectal cancer", Diseases of the Colon and Rectum, vol. 53, no. 5, pp. 830-837, 2010. AbstractWebsite

PURPOSE: Lifestyle factors and environmental exposures might help explain the risk of colorectal carcinoma in countries where the incidence is low, but unique patterns of young onset and a high proportion of rectal cancer exist. METHODS: We obtained detailed lifestyle information from 421 patients with colorectal cancer and 439 hospital-controls in Egypt. Logistic regression models were computed to evaluate the risk factors of colorectal carcinoma. RESULTS: A history of pesticide exposure and more frequently eating food directly from farms were significantly associated with a higher risk of colorectal carcinoma (odds ratio = 2.6; 95% CI = 1.1-5.9, and odds ratio = 4.6; 95% CI = 1.5-14.6, respectively). Parous women who reported 7 or more live births or breastfed for 19 months or longer per live birth had a significantly lower risk for colorectal carcinoma (odds ratio = 0.3; 95% CI = 0.2-0.7, and odds ratio = 0.2; 95% CI = 0.1-0.4, respectively). Compared with patients aged 40 years or older, industrial exposures were more common in younger patients (P =.05). CONCLUSIONS: Agricultural and industrial exposures were associated with increased risk of colorectal carcinoma, whereas prolonged lactation and increased parity were inversely associated with colorectal carcinoma in women. Further research to elucidate the biological role of intense environmental and industrial exposures and reproductive factors including lactation may further clarify the etiology of colorectal cancer.

Lo, A. - C. a, A. S. a Soliman, H. M. b Khaled, A. c Aboelyazid, and J. K. d Greenson, "Lifestyle, occupational, and reproductive factors and risk of colorectal cancer", Diseases of the Colon and Rectum, vol. 53, no. 5, pp. 830-837, 2010. AbstractWebsite

PURPOSE: Lifestyle factors and environmental exposures might help explain the risk of colorectal carcinoma in countries where the incidence is low, but unique patterns of young onset and a high proportion of rectal cancer exist. METHODS: We obtained detailed lifestyle information from 421 patients with colorectal cancer and 439 hospital-controls in Egypt. Logistic regression models were computed to evaluate the risk factors of colorectal carcinoma. RESULTS: A history of pesticide exposure and more frequently eating food directly from farms were significantly associated with a higher risk of colorectal carcinoma (odds ratio = 2.6; 95% CI = 1.1-5.9, and odds ratio = 4.6; 95% CI = 1.5-14.6, respectively). Parous women who reported 7 or more live births or breastfed for 19 months or longer per live birth had a significantly lower risk for colorectal carcinoma (odds ratio = 0.3; 95% CI = 0.2-0.7, and odds ratio = 0.2; 95% CI = 0.1-0.4, respectively). Compared with patients aged 40 years or older, industrial exposures were more common in younger patients (P =.05). CONCLUSIONS: Agricultural and industrial exposures were associated with increased risk of colorectal carcinoma, whereas prolonged lactation and increased parity were inversely associated with colorectal carcinoma in women. Further research to elucidate the biological role of intense environmental and industrial exposures and reproductive factors including lactation may further clarify the etiology of colorectal cancer.

Khaled, H., and H. Kamel, "Preface", Journal of Advanced Research, vol. 1, no. 1, pp. 1, 2010. AbstractWebsite
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Khaled, H., and H. Kamel, "Preface", Journal of Advanced Research, vol. 1, no. 1, pp. 1, 2010. AbstractWebsite
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Eissa, S. S. a, N. b Block, H. M. c Khaled, S. H. a Shoman, M. d Nassiri, and M. d Nadji, "Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases", Journal of Advanced Research, vol. 1, no. 2, pp. 151-156, 2010. AbstractWebsite

Primary enteric-type adenocarcinoma of the urinary bladder is relatively uncommon. We present our experience with 109 pure, non-urachal cases-the largest series to date. This work was undertaken with the aim of describing the immunohistochemical features of adenocarcinoma of the urinary bladder associated with schistosomiasis, illustrating their histologic and immunohistochemical similarities to colorectal carcinomas. Partial or total cystectomy specimens from a cohort of Egyptian and American patients with the diagnosis of primary adenocarcinoma of the urinary bladder (109 cases) were reviewed. Paraffin sections of each tumour were stained using the labelled streptavidin-biotin method using antibodies cytokeratin 20, cytokeratin 7, CDX2, MLH1, and villin. Clinical follow-up was available for at least 36 months. An enteric (colonic) morphology was seen in most tumours; some with signet ring cells or mucinous elements. Five tumours were composed predominantly of signet ring cells and two demonstrated a pure mucinous morphology. In cases where adjacent normal mucosa was present, 23% showed either colonic metaplasia or intestinal-type cystitis glandularis. Furthermore, 24% of enteric-type adenocarcinomas had associated villous or tubulovillous adenomas with or without dysplasia. Cytokeratin 20 was expressed by 90%, cytokeratin 7 by 17%, CDX2 by 100% and villin and MLH1 by 76% and 48% of tumours respectively. The majority of tumours presented with an advanced stage and followed an aggressive clinical course.In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar - if not identical - to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas. © 2010 Cairo University.

Eissa, S. S. a, N. b Block, H. M. c Khaled, S. H. a Shoman, M. d Nassiri, and M. d Nadji, "Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases", Journal of Advanced Research, vol. 1, no. 2, pp. 151-156, 2010. AbstractWebsite

Primary enteric-type adenocarcinoma of the urinary bladder is relatively uncommon. We present our experience with 109 pure, non-urachal cases-the largest series to date. This work was undertaken with the aim of describing the immunohistochemical features of adenocarcinoma of the urinary bladder associated with schistosomiasis, illustrating their histologic and immunohistochemical similarities to colorectal carcinomas. Partial or total cystectomy specimens from a cohort of Egyptian and American patients with the diagnosis of primary adenocarcinoma of the urinary bladder (109 cases) were reviewed. Paraffin sections of each tumour were stained using the labelled streptavidin-biotin method using antibodies cytokeratin 20, cytokeratin 7, CDX2, MLH1, and villin. Clinical follow-up was available for at least 36 months. An enteric (colonic) morphology was seen in most tumours; some with signet ring cells or mucinous elements. Five tumours were composed predominantly of signet ring cells and two demonstrated a pure mucinous morphology. In cases where adjacent normal mucosa was present, 23% showed either colonic metaplasia or intestinal-type cystitis glandularis. Furthermore, 24% of enteric-type adenocarcinomas had associated villous or tubulovillous adenomas with or without dysplasia. Cytokeratin 20 was expressed by 90%, cytokeratin 7 by 17%, CDX2 by 100% and villin and MLH1 by 76% and 48% of tumours respectively. The majority of tumours presented with an advanced stage and followed an aggressive clinical course.In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar - if not identical - to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas. © 2010 Cairo University.

2009
Khaled, H. M., A. A. Bahnassy, A. A. Raafat, A. - R. N. Zekri, M. S. Madboul, and N. M. Mokhtar, "Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer.", BMC cancer, vol. 9, pp. 32, 2009. Abstract

BACKGROUND: Clinical characterization of bladder carcinomas is still inadequate using the standard clinico-pathological prognostic markers. We assessed the correlation between nm23-H1, Rb, EGFR and p53 in relation to the clinical outcome of patients with muscle invasive bilharzial bladder cancer (MI-BBC).

METHODS: nm23-H1, Rb, EGFR and p53 expression was assessed in 59 MI-BBC patients using immunohistochemistry and reverse transcription (RT-PCR) and was correlated to the standard clinico-pathological prognostic factors, patient's outcome and the overall survival (OS) rate.

RESULTS: Overexpression of EGFR and p53 proteins was detected in 66.1% and 35.6%; respectively. Loss of nm23-H1and Rb proteins was detected in 42.4% and 57.6%; respectively. Increased EGFR and loss of nm23-H1 RNA were detected in 61.5% and 36.5%; respectively. There was a statistically significant correlation between p53 and EGFR overexpression (p < 0.0001), nm23 loss (protein and RNA), lymph node status (p < 0.0001); between the incidence of local recurrence and EGFR RNA overexpression (p= 0.003) as well as between the incidence of metastasis and altered Rb expression (p = 0.026), p53 overexpression (p < 0.0001) and mutation (p = 0.04). Advanced disease stage correlated significantly with increased EGFR (protein and RNA) (p = 0.003 & 0.01), reduced nm23-H1 RNA (p = 0.02), altered Rb (p = 0.023), and p53 overexpression (p = 0.004). OS rates correlated significantly, in univariate analysis, with p53 overexpression (p = 0.011), increased EGFR (protein and RNA, p = 0.034&0.031), nm23-H1 RNA loss (p = 0.021) and aberrations of > or = 2 genes. However, multivariate analysis showed that only high EGFR overexpression, metastatic recurrence, high tumor grade and the combination of > or = 2 affected markers were independent prognostic factors.

CONCLUSION: nm23-H1, EGFR and p53 could be used as prognostic biomarkers in MI-BBC patients. In addition to the standard pathological prognostic factors, a combination of these markers (> or = 2) has synergistic effects in stratifying patients into variable risk groups. The higher is the number of altered biomarkers, the higher will be the risk of disease progression and death.

Ismail, M. F., M. S. Aly, H. M. Khaled, and H. M. Mohamed, "Detection of HER-2/neu, c-myc amplification and p53 inactivation by FISH in Egyptian patients with breast cancer.", German medical science : GMS e-journal, vol. 7, pp. Doc03, 2009. Abstract

Breast cancer is a leading cause of cancer-related deaths in women worldwide. The clinical course of this disease is highly variable and clinicians continuously search for prognostic parameters that can accurately predict prognosis, and indicate a suitable adjuvant therapy for each patient. Amplification of the two oncogenes HER-2/neu and c-myc and inactivation of the tumor suppressor gene p53 are frequently encountered in breast carcinomas. The purpose of this study was to use the fluorescence in situ hybridization (FISH) for the assessment of HER-2/neu and c-myc amplification and p53 inactivation and to relate these molecular markers with the commonly used clinical and pathological factors. The study was conducted on 34 tissue samples obtained from 33 females and 1 male with breast carcinomas and 17 samples obtained from 16 females and 1 male with benign breast lesions. Results revealed that the level of HER-2/neu, c-myc and p53 in the malignant group was significantly increased as compared to the benign group. On relating the level of the molecular markers to clinicopathological factors, p53 was significantly associated with increased patient's age. The sensitivity of the investigated markers significantly increased with larger tumor size. Concerning tumor grade, HER-2/neu and p53 showed a significant increase in low-grade tumors whereas c-myc showed a highly significant increase in high-grade tumors. With regard to disease staging, HER-2/neu and c-myc were the only markers that showed significant increase at late stages of disease. p53 and HER-2/neu were significantly associated with positive lymph nodal status. A significant correlation was obtained between the levels of the three biomarkers to each other. Conclusively, the combination of HER-2/neu, c-myc and p53 can stratify patients into different risk groups.

Lo, A. - C. a, A. a Georgopoulos, C. G. b Kleer, M. c Banerjee, S. d Omar, H. d Khaled, S. d Eissa, A. e Hablas, H. G. f Omar, J. A. g Douglas, et al., "Analysis of RhoC expression and lymphovascular emboli in inflammatory vs non-inflammatory breast cancers in Egyptian patients", Breast, vol. 18, no. 1, pp. 55-59, 2009. AbstractWebsite

Understanding the molecular factors that distinguish inflammatory breast cancer (IBC) from non-IBC is important for IBC diagnosis. We reviewed the records of 48 IBC patients and 64 non-IBC patients from Egypt. We determined RhoC expression and tumor emboli and their relationship to demographic and reproductive characteristics. Compared with non-IBC patients, IBC patients had significantly lower parity (P = 0.018) and fewer palpable tumors (P < 0.0001). IBC tumors showed RhoC overexpression more frequently than non-IBC tumors (87% vs. 17%, respectively) (P < 0.0001). Tumor emboli were significantly more frequent in IBC tumors than non-IBC tumors (Mean ± SD: 14.1 ± 14.0 vs. 7.0 ± 12.9, respectively) (P < 0.0001). This study illustrates that RhoC overexpression and tumor emboli are more frequent in tumors of IBC relative to non-IBC from Egypt. Future studies should focus on relating epidemiologic factors to molecular features of IBC in this population. © 2008 Elsevier Ltd. All rights reserved.