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2004
el-Din, H. M., M. A. Attia, M. R. Hamza, H. M. Khaled, M. A. Thoraya, and S. A. Eisa, "Hepatitis C Virus and related changes in immunological parameters in non Hodgkin's lymphoma patients.", Egypt J Immunol, vol. 11, no. 1, pp. 55-64, 2004. AbstractWebsite

{Viral hepatitis is a common and important problem in immunocompromised cancer patients. The present study was conducted to investigate changes in some cellular and humoral immunological parameters as a consequence of HCV infection in non Hodgkin's lymphoma patients (NHL). The study included 40 NHL patients: 20 anti-HCV antibody positive (Gr. I ), and 20 anti-HCV antibody negative (Gr.II ). In addition, forty non-cancer controls (NCCs) were included: 20 of them were anti-HCV antibody positive (Gr. III) and 20 anti-HCV antibody negative (Gr. IV). The studied immunological parameters included serum levels of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), and soluble tumor necrosis factor receptors (s-TNFr) measured by ELISA, as well as assessment of T and B lymphocyte subsets by PAP immunostaining method. Mean IL-1 level (pg/ml) was significantly higher in Gr. 1 (14 +/- 6) and Gr. III (20 +/- 12) as compared to those in Gr. II (7 +/- 5) and Gr. IV (9 +/- 6). Mean IL-2 level (pg/ml) was also significantly higher in Gr. I (132 +/- 101) and Gr. III (135 +/- 59) compared to those in Gr. II (36 +/- 29) and Gr. IV (31 +/- 48). On the other hand, level of IL-6 showed no significant difference between groups. The mean level of sTNF-r, (ng/ml) was only significantly higher in Gr. I (2.9 +/- 1.7) when compared to that in Gr. IV (1.9 +/- 2.2). In group IV, the average percentage of CD3 (70 +/- 4%) and CD4 (44 +/- 5%) were significantly higher than in those of Gr. I (CD3 = 51 +/- 11%

Naresh, K. N. a, S. a Advani, M. a Adde, Z. a Aziz, S. a Banavali, K. a Bhatia, A. a Belgaumi, A. A. Ezzat, M.I. and Sleem, H. a Khaled, N. a Mokhtar, et al., "Report of an International Network of Cancer Treatment and Research workshop on non-Hodgkin's lymphoma in developing countries", Blood Cells, Molecules, and Diseases, vol. 33, no. 3, pp. 330-337, 2004. AbstractWebsite

The International Network of Cancer Treatment and Research (INCTR) recently organized a workshop on non-Hodgkin lymphomas (NHLs) in selected developing countries with the purpose of examining existing information relating to the pathology and management of these neoplasms, and identifying potential areas for research. This report provides a summary of the information presented and is focused primarily on the pathology of NHLs in children and adults. In most countries, the WHO classification of lymphomas was used and most participating centers included immunohistochemistry using a wide array of lymphoid antibodies as part of routine diagnosis. Some of the series had been reviewed by an external panel of experts. B-cell lymphomas accounted for 82-88% of all NHLs. The proportions of chronic lymphatic leukemia (4-6%), mantle cell lymphoma (MCL, 3-5%), and plasmacytoma (2-4%) were similar in the series presented. However, there was a significant variation in the proportion of follicular lymphoma (FL), which accounted for 15% and 11% in India and Kuwait, but less than 5% in Pakistan and Egypt. All of these frequencies are significantly lower than those reported in Western series. Diffuse large B-cell lymphoma accounted for about 35% of cases in India but for more 50% in other countries, but this difference was not accounted for by an increased incidence in a single lymphoma subtype in India, but rather an apparent paucity of several subtypes (such as mantle cell and marginal zone lymphomas (MZL)) in other series. There were relatively high frequencies of Burkitt lymphoma in Egypt (7%) and precursor T-cell lymphoblastic lymphoma in India (6-7%). Peripheral T-cell lymphomas (PTCLs) (not otherwise specified and angioimmunoblastic subtypes) accounted for 3-5% of NHLs, and extranodal lymphoma of T/NK cell type was rare (<1%). These differences in the relative proportions of NHL subtypes among developing countries and between developing countries and the rest of the world presumably arise from differences in environmental and genetic factors that influence lymphomagenesis and strongly suggest that more research in developing countries would provide valuable insights into the pathogenesis of lymphoid neoplasms.

Naresh, K. N. a, S. a Advani, M. a Adde, Z. a Aziz, S. a Banavali, K. a Bhatia, A. a Belgaumi, A. A. Ezzat, M.I. and Sleem, H. a Khaled, N. a Mokhtar, et al., "Report of an International Network of Cancer Treatment and Research workshop on non-Hodgkin's lymphoma in developing countries", Blood Cells, Molecules, and Diseases, vol. 33, no. 3, pp. 330-337, 2004. AbstractWebsite

The International Network of Cancer Treatment and Research (INCTR) recently organized a workshop on non-Hodgkin lymphomas (NHLs) in selected developing countries with the purpose of examining existing information relating to the pathology and management of these neoplasms, and identifying potential areas for research. This report provides a summary of the information presented and is focused primarily on the pathology of NHLs in children and adults. In most countries, the WHO classification of lymphomas was used and most participating centers included immunohistochemistry using a wide array of lymphoid antibodies as part of routine diagnosis. Some of the series had been reviewed by an external panel of experts. B-cell lymphomas accounted for 82-88% of all NHLs. The proportions of chronic lymphatic leukemia (4-6%), mantle cell lymphoma (MCL, 3-5%), and plasmacytoma (2-4%) were similar in the series presented. However, there was a significant variation in the proportion of follicular lymphoma (FL), which accounted for 15% and 11% in India and Kuwait, but less than 5% in Pakistan and Egypt. All of these frequencies are significantly lower than those reported in Western series. Diffuse large B-cell lymphoma accounted for about 35% of cases in India but for more 50% in other countries, but this difference was not accounted for by an increased incidence in a single lymphoma subtype in India, but rather an apparent paucity of several subtypes (such as mantle cell and marginal zone lymphomas (MZL)) in other series. There were relatively high frequencies of Burkitt lymphoma in Egypt (7%) and precursor T-cell lymphoblastic lymphoma in India (6-7%). Peripheral T-cell lymphomas (PTCLs) (not otherwise specified and angioimmunoblastic subtypes) accounted for 3-5% of NHLs, and extranodal lymphoma of T/NK cell type was rare (<1%). These differences in the relative proportions of NHL subtypes among developing countries and between developing countries and the rest of the world presumably arise from differences in environmental and genetic factors that influence lymphomagenesis and strongly suggest that more research in developing countries would provide valuable insights into the pathogenesis of lymphoid neoplasms.

2003
Khaled, H. M., A. A. Bahnassi, A. - R. N. Zekri, H. A. Kassem, and N. Mokhtar, "Correlation between p53 mutations and HPV in bilharzial bladder cancer.", Urologic oncology, vol. 21, issue 5, pp. 334-41, 2003 Sep-Oct. Abstract

Alterations of the p53 tumor suppressor gene are the most common genetic changes detected in human cancers as well as in papillary and invasive bladder cancer. Several studies have demonstrated an association between HPV infection and urological malignancies. In the present work, the p53 gene status was studied together with the frequency of HPV in 99 cases of Bilharzial bladder cancer [BBC] in Egypt and both were correlated to the clinicopathological features of the patients. SSCP and sequencing were used to screen the p53 gene for mutations at exons 4-10 and IHC was performed to detect protein overexpression. PCR was used for detection and typing of HPV-DNA in tumor samples. p53 mutations were detected in 33.3% of the studied cases whereas protein overexpression was detected in 35.6% of the cases. The highest concordance rate was observed in cases harboring mutations at exon 4 [87.5%]. Bilharzial infestation was obvious in 72.2% of the cases that showed mutations. Exon 8 showed the highest rate of mutation [32%] followed by exons 4 and 5 [22% each]. The commonest mutational event was G:C transversion [15/50] especially at CpG dinucleotides. A mutational hot spot was detected at exon 4, codons 72-73. HPV-DNA was detected in 48.97% of the cases the majority of which [64.6%] were of type 16. Significant correlation was found between p53 mutation and the pathological stage as well as p53 overexpression and tumor grade. Our results demonstrate that the mutational spectrum in BBC is different from that of bladder cancer in Western countries in many aspects and suggest an etiological role of HPV in this type of neoplasm. However, both HPV infection and p53 gene abnormalities may contribute to Bilharzial bladder carcinogenesis in an independent way.

Khaled, H. M., A. A. Bahnassi, A. - R. N. Zekri, H. A. Kassem, and N. Mokhtar, "Correlation between p53 mutations and HPV in bilharzial bladder cancer.", Urologic oncology, vol. 21, issue 5, pp. 334-41, 2003 Sep-Oct. Abstract

Alterations of the p53 tumor suppressor gene are the most common genetic changes detected in human cancers as well as in papillary and invasive bladder cancer. Several studies have demonstrated an association between HPV infection and urological malignancies. In the present work, the p53 gene status was studied together with the frequency of HPV in 99 cases of Bilharzial bladder cancer [BBC] in Egypt and both were correlated to the clinicopathological features of the patients. SSCP and sequencing were used to screen the p53 gene for mutations at exons 4-10 and IHC was performed to detect protein overexpression. PCR was used for detection and typing of HPV-DNA in tumor samples. p53 mutations were detected in 33.3% of the studied cases whereas protein overexpression was detected in 35.6% of the cases. The highest concordance rate was observed in cases harboring mutations at exon 4 [87.5%]. Bilharzial infestation was obvious in 72.2% of the cases that showed mutations. Exon 8 showed the highest rate of mutation [32%] followed by exons 4 and 5 [22% each]. The commonest mutational event was G:C transversion [15/50] especially at CpG dinucleotides. A mutational hot spot was detected at exon 4, codons 72-73. HPV-DNA was detected in 48.97% of the cases the majority of which [64.6%] were of type 16. Significant correlation was found between p53 mutation and the pathological stage as well as p53 overexpression and tumor grade. Our results demonstrate that the mutational spectrum in BBC is different from that of bladder cancer in Western countries in many aspects and suggest an etiological role of HPV in this type of neoplasm. However, both HPV infection and p53 gene abnormalities may contribute to Bilharzial bladder carcinogenesis in an independent way.

Gee, J. R., R. G. Montoya, H. M. Khaled, A. L. Sabichi, and B. H. Grossman, "Cytokeratin 20, AN43, PGDH, and COX-2 expression in transitional and squamous cell carcinoma of the bladder.", Urologic oncology, vol. 21, issue 4, pp. 266-70, 2003 Jul-Aug. Abstract

Bladder tumors from Egyptian patients with a high prevalence of bilharziasis were immunohistochemically analyzed for the expression of cytokeratin 20 (CK20), AN43, prostaglandin dehydrogenase (PGDH), and cyclooxygenase-2 (COX-2). The tumors included 26 transitional cell carcinomas (TCC), 10 squamous cell carcinomas (SCC) and 2 tumors of mixed TCC/SCC histology. Of the 28 TCC tumors, 21 (75%) expressed CK20 and 25 (89%) expressed AN43. CK20 was not expressed in any of the 10 SCC tumors and AN43 was expressed in 2 of them. PGDH was expressed in 18 (64%) of the 28 tumors with TCC histology and 1 of the 10 SCC. A subset of 21 tumors (16 TCC and 5 SCC) was tested for COX-2 expression. COX-2 was detected in 69% of the 16 TCC tumors examined but was not seen in the SCC tumors. As tumors increased in stage, the expression of these proteins changed. CK20, AN43 and PGDH decreased but COX-2 expression increased in higher stage tumors. The histologic phenotype of these cancers is reflected in their expression of these proteins and is modified further as tumors progress in stage.

Gee, J. R., R. G. Montoya, H. M. Khaled, A. L. Sabichi, and B. H. Grossman, "Cytokeratin 20, AN43, PGDH, and COX-2 expression in transitional and squamous cell carcinoma of the bladder.", Urologic oncology, vol. 21, issue 4, pp. 266-70, 2003 Jul-Aug. Abstract

Bladder tumors from Egyptian patients with a high prevalence of bilharziasis were immunohistochemically analyzed for the expression of cytokeratin 20 (CK20), AN43, prostaglandin dehydrogenase (PGDH), and cyclooxygenase-2 (COX-2). The tumors included 26 transitional cell carcinomas (TCC), 10 squamous cell carcinomas (SCC) and 2 tumors of mixed TCC/SCC histology. Of the 28 TCC tumors, 21 (75%) expressed CK20 and 25 (89%) expressed AN43. CK20 was not expressed in any of the 10 SCC tumors and AN43 was expressed in 2 of them. PGDH was expressed in 18 (64%) of the 28 tumors with TCC histology and 1 of the 10 SCC. A subset of 21 tumors (16 TCC and 5 SCC) was tested for COX-2 expression. COX-2 was detected in 69% of the 16 TCC tumors examined but was not seen in the SCC tumors. As tumors increased in stage, the expression of these proteins changed. CK20, AN43 and PGDH decreased but COX-2 expression increased in higher stage tumors. The histologic phenotype of these cancers is reflected in their expression of these proteins and is modified further as tumors progress in stage.

Ismail, S. M., W. Wynendaele, J. L. E. Aerts, R. Paridaens, L. Van Mellaert, J. Anné, R. Gaafar, N. Shakankiry, H. M. Khaled, M. R. Christiaens, et al., "Real-time quantitative RT-PCR and detection of tumour cell dissemination in breast cancer patients: plasmid versus cell line dilutions.", Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, vol. 14, issue 8, pp. 1241-5, 2003 Aug. Abstract

BACKGROUND: We previously developed a real-time quantitative RT-PCR technique to detect breast carcinoma cells in peripheral blood (PB). The aim of the current study was to improve cytokeratin 19 (CK19) quantification using plasmid dilutions of cloned PCR fragments to obtain a more reliable and reproducible quantification of CK19 transcripts.

MATERIALS AND METHODS: PB samples of 14 stage IV breast cancer patients and 23 healthy controls were examined with RT-PCR using plasmid quantification.

RESULTS: Median CK19+ copy numbers of one and 11 were detected in the control group and stage IV breast cancer patients, respectively (Mann-Whitney, P

Ismail, S. M., W. Wynendaele, J. L. E. Aerts, R. Paridaens, L. Van Mellaert, J. Anné, R. Gaafar, N. Shakankiry, H. M. Khaled, M. R. Christiaens, et al., "Real-time quantitative RT-PCR and detection of tumour cell dissemination in breast cancer patients: plasmid versus cell line dilutions.", Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, vol. 14, issue 8, pp. 1241-5, 2003 Aug. Abstract

BACKGROUND: We previously developed a real-time quantitative RT-PCR technique to detect breast carcinoma cells in peripheral blood (PB). The aim of the current study was to improve cytokeratin 19 (CK19) quantification using plasmid dilutions of cloned PCR fragments to obtain a more reliable and reproducible quantification of CK19 transcripts.

MATERIALS AND METHODS: PB samples of 14 stage IV breast cancer patients and 23 healthy controls were examined with RT-PCR using plasmid quantification.

RESULTS: Median CK19+ copy numbers of one and 11 were detected in the control group and stage IV breast cancer patients, respectively (Mann-Whitney, P

Omar, S. a, H. a Khaled, R. a Gaafar, A. R. a Zekry, S. a Eissa, and O. b El-Khatib, "Breast cancer in Egypt: A review of disease presentation and detection strategies", Eastern Mediterranean Health Journal, vol. 9, no. 3, pp. 448-463, 2003. AbstractWebsite

Carcinoma of the breast is the most prevalent cancer among Egyptian women and constitutes 29% of National Cancer Institute cases. Median age at diagnosis is one decade younger than in countries of Europe and North America and most patients are premenopausal. Tumours are relatively advanced at presentation. The majority of tumours are invasive duct subtype and the profile of hormone receptors is positive for estrogen receptors and/or progesterone receptors in less than half of cases. This overview examines genetic changes, potential and established predictive and prognostic markers and end results of surgery, radiotherapy and systemic therapy for early, locally advanced and metastatic disease stages. Disease presentations common to the region and early detection strategies are presented.

Khaled, H. M. a, A. A. b Bahnassi, A. - R. N. c Zekri, H. A. d Kassem, and N. b Mokhtar, "Correlation between p53 mutations and HPV in bilharzial bladder cancer", Urologic Oncology: Seminars and Original Investigations, vol. 21, no. 5, pp. 334-341, 2003. AbstractWebsite

Alterations of the p53 tumor suppressor gene are the most common genetic changes detected in human cancers as well as in papillary and invasive bladder cancer. Several studies have demonstrated an association between HPV infection and urological malignancies. In the present work, the p53 gene status was studied together with the frequency of HPV in 99 cases of Bilharzial bladder cancer [BBC] in Egypt and both were correlated to the clinicopathological features of the patients. SSCP and sequencing were used to screen the p53 gene for mutations at exons 4-10 and IHC was performed to detect protein overexpression. PCR was used for detection and typing of HPV-DNA in tumor samples. p53 mutations were detected in 33.3% of the studied cases whereas protein overexpression was detected in 35.6% of the cases. The highest concordance rate was observed in cases harboring mutations at exon 4 [87.5%]. Bilharzial infestation was obvious in 72.2% of the cases that showed mutations. Exon 8 showed the highest rate of mutation [32%] followed by exons 4 and 5 [22% each]. The commonest mutational event was G:C transversion [15/50] especially at CpG dinucleotides. A mutational hot spot was detected at exon 4, codons 72-73. HPV-DNA was detected in 48.97% of the cases the majority of which [64.6%] were of type 16. Significant correlation was found between p53 mutation and the pathological stage as well as p53 overexpression and tumor grade. Our results demonstrate that the mutational spectrum in BBC is different from that of bladder cancer in Western countries in many aspects and suggest an etiological role of HPV in this type of neoplasm. However, both HPV infection and p53 gene abnormalities may contribute to Bilharzial bladder carcinogenesis in an independent way. © 2003 Elsevier Inc. All rights reserved.

Khaled, H. M. a, A. A. b Bahnassi, A. - R. N. c Zekri, H. A. d Kassem, and N. b Mokhtar, "Correlation between p53 mutations and HPV in bilharzial bladder cancer", Urologic Oncology: Seminars and Original Investigations, vol. 21, no. 5, pp. 334-341, 2003. AbstractWebsite

Alterations of the p53 tumor suppressor gene are the most common genetic changes detected in human cancers as well as in papillary and invasive bladder cancer. Several studies have demonstrated an association between HPV infection and urological malignancies. In the present work, the p53 gene status was studied together with the frequency of HPV in 99 cases of Bilharzial bladder cancer [BBC] in Egypt and both were correlated to the clinicopathological features of the patients. SSCP and sequencing were used to screen the p53 gene for mutations at exons 4-10 and IHC was performed to detect protein overexpression. PCR was used for detection and typing of HPV-DNA in tumor samples. p53 mutations were detected in 33.3% of the studied cases whereas protein overexpression was detected in 35.6% of the cases. The highest concordance rate was observed in cases harboring mutations at exon 4 [87.5%]. Bilharzial infestation was obvious in 72.2% of the cases that showed mutations. Exon 8 showed the highest rate of mutation [32%] followed by exons 4 and 5 [22% each]. The commonest mutational event was G:C transversion [15/50] especially at CpG dinucleotides. A mutational hot spot was detected at exon 4, codons 72-73. HPV-DNA was detected in 48.97% of the cases the majority of which [64.6%] were of type 16. Significant correlation was found between p53 mutation and the pathological stage as well as p53 overexpression and tumor grade. Our results demonstrate that the mutational spectrum in BBC is different from that of bladder cancer in Western countries in many aspects and suggest an etiological role of HPV in this type of neoplasm. However, both HPV infection and p53 gene abnormalities may contribute to Bilharzial bladder carcinogenesis in an independent way. © 2003 Elsevier Inc. All rights reserved.

Gee, J. R. a, R. G. a Montoya, H. M. b Khaled, A. L. c Sabichi, and H. B. a Grossman, "Cytokeratin 20, AN43, PGDH, and COX-2 expression in transitional and squamous cell carcinoma of the bladder", Urologic Oncology: Seminars and Original Investigations, vol. 21, no. 4, pp. 266-270, 2003. AbstractWebsite

Bladder tumors from Egyptian patients with a high prevalence of bilharziasis were immunohistochemically analyzed for the expression of cytokeratin 20 (CK20), AN43, prostaglandin dehydrogenase (PGDH), and cyclooxygenase-2 (COX-2). The tumors included 26 transitional cell carcinomas (TCC), 10 squamous cell carcinomas (SCC) and 2 tumors of mixed TCC/SCC histology. Of the 28 TCC tumors, 21 (75%) expressed CK20 and 25 (89%) expressed AN43. CK20 was not expressed in any of the 10 SCC tumors and AN43 was expressed in 2 of them. PGDH was expressed in 18 (64%) of the 28 tumors with TCC histology and 1 of the 10 SCC. A subset of 21 tumors (16 TCC and 5 SCC) was tested for COX-2 expression. COX-2 was detected in 69% of the 16 TCC tumors examined but was not seen in the SCC tumors. As tumors increased in stage, the expression of these proteins changed. CK20, AN43 and PGDH decreased but COX-2 expression increased in higher stage tumors. The histologic phenotype of these cancers is reflected in their expression of these proteins and is modified further as tumors progress in stage. © 2003 Elsevier Inc. All rights reserved.

b Saad Ismail, M. a, W. a Wynendaele, J. L. E. c Aerts, R. a Paridaens, L. d Van Mellaert, J. d Anné, R. b Gaafar, N. b Shakankiry, H. M. b Khaled, M. R. a Christiaens, et al., "Real-time quantitative RT-PCR and detection of tumour cell dissemination in breast cancer patients: Plasmid versus cell line dilutions", Annals of Oncology, vol. 14, no. 8, pp. 1241-1245, 2003. AbstractWebsite

Background: We previously developed a real-time quantitative RT-PCR technique to detect breast carcinoma cells in peripheral blood (PB). The aim of the current study was to improve cytokeratin 19 (CK19) quantification using plasmid dilutions of cloned PCR fragments to obtain a more reliable and reproducible quantification of CK19 transcripts. Materials and methods: PB samples of 14 stage IV breast cancer patients and 23 healthy controls were examined with RT-PCR using plasmid quantification. Results: Median CK19+ copy numbers of one and 11 were detected in the control group and stage IV breast cancer patients, respectively (Mann-Whitney, P≤0.0001). When comparing the results obtained using cell line dilutions with those obtained using plasmid dilutions, a good correlation was observed (r2=0.98). Conclusions: Plasmid dilutions are more reliable than cell line dilutions for quantification of gene expression, and more objective criteria for positivity could be defined based on the characteristics of the standard curve (slope and intercept). A more universally accepted agreement on the definition of the cut-off value for positivity is needed.

2002
Aly, M. S., and H. M. Khaled, "Chromosomal aberrations in early-stage bilharzial bladder cancer.", Cancer genetics and cytogenetics, vol. 132, issue 1, pp. 41-5, 2002 Jan 1. Abstract

Bilharzial bladder cancer is one of the most common types of malignancy in both men and women in several developing countries including Egypt. It has several unique clinical, epidemiological, and histological characteristics, suggesting that it is an entity distinct from bladder cancer seen in Western countries. Genetic alterations in bilharzial-related bladder cancer have been studied infrequently, especially in the advanced stages of disease, that is, T3 and T4 classifications. The objective of this study was to extend establishing the baseline cytogenetic profile of this type of malignancy to early T1 and T2 classifications. For this purpose, fluorescence in situ hybridization was applied to interphase nuclei of frozen-stored samples with biotinylated repetitive DNA probes specific for all chromosomes to detect numerical chromosome changes in 35 patients presenting with relatively early-stage pT1 and pT2 disease. Eleven cases had squamous cell carcinoma (SCC) and 24 had transitional cell carcinoma. Six of 24 transitional cell carcinomas had diploid chromosome counts with all the probes. Numerical chromosome aberrations were detected in 18 cases (75%). In 12 cases, a loss of chromosome 9 was observed. In three cases, an additional loss of chromosome 17 was detected. One case demonstrated a loss of chromosome 10, whereas another two cases showed a gain of chromosome 7, next to a loss of chromosome 9. Loss of chromosome Y was observed in nine of the 27 male cases studied (33.3%), in which only one case showed an abnormality whereas four cases were detected next to loss of chromosome 9, and one case showed gain of chromosome 7. Five cases showed loss of chromosome 19 whereas gain of chromosome 4 was detected in two cases. Two of 11 samples of SCC had normal diploid chromosome counts with all the probes used. In four of 11 cases (36.4%) underrepresentation of chromosome 9, compared with the other chromosomes, was detected. An additional loss of chromosome 17 and gain of chromosome 7, next to loss of chromosome 9, was detected in three cases. One case showed loss of chromosome 17 as the only numerical aberration. Loss of the Y chromosome was detected in three cases of which one case had gain of chromosome 7 and one case had loss of chromosome 19. No correlation was found between any of the clinicopathologic parameters examined in this study and the presence or absence of any numerical chromosomal aberrations except for the significant association between schistosomal history and loss of Y chromosome (P=0.007).

Aly, M. S., and H. M. Khaled, "Chromosomal aberrations in early-stage bilharzial bladder cancer.", Cancer genetics and cytogenetics, vol. 132, issue 1, pp. 41-5, 2002 Jan 1. Abstract

Bilharzial bladder cancer is one of the most common types of malignancy in both men and women in several developing countries including Egypt. It has several unique clinical, epidemiological, and histological characteristics, suggesting that it is an entity distinct from bladder cancer seen in Western countries. Genetic alterations in bilharzial-related bladder cancer have been studied infrequently, especially in the advanced stages of disease, that is, T3 and T4 classifications. The objective of this study was to extend establishing the baseline cytogenetic profile of this type of malignancy to early T1 and T2 classifications. For this purpose, fluorescence in situ hybridization was applied to interphase nuclei of frozen-stored samples with biotinylated repetitive DNA probes specific for all chromosomes to detect numerical chromosome changes in 35 patients presenting with relatively early-stage pT1 and pT2 disease. Eleven cases had squamous cell carcinoma (SCC) and 24 had transitional cell carcinoma. Six of 24 transitional cell carcinomas had diploid chromosome counts with all the probes. Numerical chromosome aberrations were detected in 18 cases (75%). In 12 cases, a loss of chromosome 9 was observed. In three cases, an additional loss of chromosome 17 was detected. One case demonstrated a loss of chromosome 10, whereas another two cases showed a gain of chromosome 7, next to a loss of chromosome 9. Loss of chromosome Y was observed in nine of the 27 male cases studied (33.3%), in which only one case showed an abnormality whereas four cases were detected next to loss of chromosome 9, and one case showed gain of chromosome 7. Five cases showed loss of chromosome 19 whereas gain of chromosome 4 was detected in two cases. Two of 11 samples of SCC had normal diploid chromosome counts with all the probes used. In four of 11 cases (36.4%) underrepresentation of chromosome 9, compared with the other chromosomes, was detected. An additional loss of chromosome 17 and gain of chromosome 7, next to loss of chromosome 9, was detected in three cases. One case showed loss of chromosome 17 as the only numerical aberration. Loss of the Y chromosome was detected in three cases of which one case had gain of chromosome 7 and one case had loss of chromosome 19. No correlation was found between any of the clinicopathologic parameters examined in this study and the presence or absence of any numerical chromosomal aberrations except for the significant association between schistosomal history and loss of Y chromosome (P=0.007).

Aly, M. S. a, and H. M. b Khaled, "Chromosomal aberrations in early-stage bilharzial bladder cancer", Cancer Genetics and Cytogenetics, vol. 132, no. 1, pp. 41-45, 2002. AbstractWebsite

Bilharzial bladder cancer is one of the most common types of malignancy in both men and women in several developing countries including Egypt. It has several unique clinical, epidemiological, and histological characteristics, suggesting that it is an entity distinct from bladder cancer seen in Western countries. Genetic alterations in bilharzial-related bladder cancer have been studied infrequently, especially in the advanced stages of disease, that is, T3 and T4 classifications. The objective of this study was to extend establishing the baseline cytogenetic profile of this type of malignancy to early T1 and T2 classifications. For this purpose, fluorescence in situ hybridization was applied to interphase nuclei of frozen-stored samples with biotinylated repetitive DNA probes specific for all chromosomes to detect numerical chromosome changes in 35 patients presenting with relatively early-stage pT1 and pT2 disease. Eleven cases had squamous cell carcinoma (SCC) and 24 had transitional cell carcinoma. Six of 24 transitional cell carcinomas had diploid chromosome counts with all the probes. Numerical chromosome aberrations were detected in 18 cases (75%). In 12 cases, a loss of chromosome 9 was observed. In three cases, an additional loss of chromosome 17 was detected. One case demonstrated a loss of chromosome 10, whereas another two cases showed a gain of chromosome 7, next to a loss of chromosome 9. Loss of chromosome Y was observed in nine of the 27 male cases studied (33.3%), in which only one case showed an abnormality whereas four cases were detected next to loss of chromosome 9, and one case showed gain of chromosome 7. Five cases showed loss of chromosome 19 whereas gain of chromosome 4 was detected in two cases. Two of 11 samples of SCC had normal diploid chromosome counts with all the probes used. In four of 11 cases (36.4%) underrepresentation of chromosome 9, compared with the other chromosomes, was detected. An additional loss of chromosome 17 and gain of chromosome 7, next to loss of chromosome 9, was detected in three cases. One case showed loss of chromosome 17 as the only numerical aberration. Loss of the Y chromosome was detected in three cases of which one case had gain of chromosome 7 and one case had loss of chromosome 19. No correlation was found between any of the clinicopathologic parameters examined in this study and the presence or absence of any numerical chromosomal aberrations except for the significant association between schistosomal history and loss of Y chromosome (P=0.007). © 2002 Elsevier Science Inc. All rights reserved.

2001
Khaled, H. M., A. Raafat, N. Mokhtar, A. R. Zekri, and H. Gaballah, "Human papilloma virus infection and overexpression of p53 protein in bilharzial bladder cancer.", Tumori, vol. 87, issue 4, pp. 256-61, 2001 Jul-Aug. Abstract

AIMS AND BACKGROUND: An association between human papilloma virus (HPV) and bladder cancer has been reported. However, the role of HPV in bilharzial bladder cancer and its prevalence have not yet been clarified.

STUDY DESIGN: We investigated 50 cases for HPV types 16/18 by in situ hybridization. Also, p53 protein expression by immunohistochemistry was evaluated in 41 of the 50 cases, with correlation of these factors to clinicopathologic parameters and tumor relapse after primary treatment.

RESULTS: HPV was detected in 46% of Egyptian bladder carcinomas (23/50 cases). Positivity was 47.8% for squamous cell carcinoma and 36.4% for transitional cell carcinoma. There was a possible viral-bilharzial association as 52.8% of Bilharzial cases, whereas only 12.5% of non-Bilharzial cases were HPV positive (P <0.05). P53 protein was found in 19/41 (46.3%) cases. There was a concordance between HPV and p53 in 58.5% of cases. Neither factor was related to tumor recurrence after primary treatment.

CONCLUSIONS: HPV may thus be implicated in the etiology of bilharzial bladder cancer, but a definite causal relationship remains to be demonstrated. HPV together with p53 alterations work in synergy to accelerate the carcinogenic process, as there was concordance in the results of both parameters in 24/41 (58.5%) cases.

Khaled, H. M., A. Raafat, N. Mokhtar, A. R. Zekri, and H. Gaballah, "Human papilloma virus infection and overexpression of p53 protein in bilharzial bladder cancer.", Tumori, vol. 87, issue 4, pp. 256-61, 2001 Jul-Aug. Abstract

AIMS AND BACKGROUND: An association between human papilloma virus (HPV) and bladder cancer has been reported. However, the role of HPV in bilharzial bladder cancer and its prevalence have not yet been clarified.

STUDY DESIGN: We investigated 50 cases for HPV types 16/18 by in situ hybridization. Also, p53 protein expression by immunohistochemistry was evaluated in 41 of the 50 cases, with correlation of these factors to clinicopathologic parameters and tumor relapse after primary treatment.

RESULTS: HPV was detected in 46% of Egyptian bladder carcinomas (23/50 cases). Positivity was 47.8% for squamous cell carcinoma and 36.4% for transitional cell carcinoma. There was a possible viral-bilharzial association as 52.8% of Bilharzial cases, whereas only 12.5% of non-Bilharzial cases were HPV positive (P <0.05). P53 protein was found in 19/41 (46.3%) cases. There was a concordance between HPV and p53 in 58.5% of cases. Neither factor was related to tumor recurrence after primary treatment.

CONCLUSIONS: HPV may thus be implicated in the etiology of bilharzial bladder cancer, but a definite causal relationship remains to be demonstrated. HPV together with p53 alterations work in synergy to accelerate the carcinogenic process, as there was concordance in the results of both parameters in 24/41 (58.5%) cases.

Abdel-Salam, I. M., H. M. Khaled, H. E. Gaballah, O. M. Mansour, H. A. A. Kassem, and A. M. Metwaly, "Telomerase activity in bilharzial bladder cancer. Prognostic implications.", Urologic oncology, vol. 6, issue 4, pp. 149-153, 2001 Jul. Abstract

Background: Bladder cancer is a common malignancy in Egypt and other developing countries in which infection with Schistosoma haematobium is prevalent. Bladder cancer caused by bilharziasis has different clinical and biological characters than that observed in the western world. In this study, we used the TRAP technique to estimate telomerase activity in bilharzial bladder cancer specimens and we correlated the findings with other clinical and pathological findings. Patients and methods: Bladder cancer specimens were obtained from 57 patients who underwent radical cystectomy and pathological diagnosis was obtained in all patients. Tissue samples were frozen in liquid nitrogen and stored at -80 degrees C. Telomerase activity by PCR-ELISA technique was measured using TRAP technique. Results: Our patient group included 45 males and 12 females with a median age of 49 years. The majority of our patients (35/57) have squamous histology and they have proven bilharzial history shown in the pathology specimens. Stage P3b was encountered in 29/57 patients whereas thirty-five patients have grade II tumors. The majority of our patients (41/57) were negative for pelvic nodes metastases. Telomerase activity was detected in 27/57 patients (47.4%). The mean level of telomerase was 0.85+/-0.77 in positive patients and 0.029+/-0.025 in negative patients. The expression of telomerase and its mean level in patients above age of 60, in males and in those with squamous pathology, higher grade of tumors or positive node was higher than those without but the difference did not reach statistical significance (P>0.05). Alternatively, expression was significantly higher in those with stages (P1-P3a) compared with P3b-P4a disease stages (66.6% vs. 37.1, P=0.03). Conclusion: Telomerase activity is increased in bilharzial bladder cancer although to a lesser degree than that reported for TCC in the western world, which could be explained, by different biological behavior or different assay methods. Further larger studies with more number of patients are still needed to determine its potential value for early detection and possible use as a therapeutic target.

Abdel-Salam, I. M., H. M. Khaled, H. E. Gaballah, O. M. Mansour, H. A. A. Kassem, and A. M. Metwaly, "Telomerase activity in bilharzial bladder cancer. Prognostic implications.", Urologic oncology, vol. 6, issue 4, pp. 149-153, 2001 Jul. Abstract

Background: Bladder cancer is a common malignancy in Egypt and other developing countries in which infection with Schistosoma haematobium is prevalent. Bladder cancer caused by bilharziasis has different clinical and biological characters than that observed in the western world. In this study, we used the TRAP technique to estimate telomerase activity in bilharzial bladder cancer specimens and we correlated the findings with other clinical and pathological findings. Patients and methods: Bladder cancer specimens were obtained from 57 patients who underwent radical cystectomy and pathological diagnosis was obtained in all patients. Tissue samples were frozen in liquid nitrogen and stored at -80 degrees C. Telomerase activity by PCR-ELISA technique was measured using TRAP technique. Results: Our patient group included 45 males and 12 females with a median age of 49 years. The majority of our patients (35/57) have squamous histology and they have proven bilharzial history shown in the pathology specimens. Stage P3b was encountered in 29/57 patients whereas thirty-five patients have grade II tumors. The majority of our patients (41/57) were negative for pelvic nodes metastases. Telomerase activity was detected in 27/57 patients (47.4%). The mean level of telomerase was 0.85+/-0.77 in positive patients and 0.029+/-0.025 in negative patients. The expression of telomerase and its mean level in patients above age of 60, in males and in those with squamous pathology, higher grade of tumors or positive node was higher than those without but the difference did not reach statistical significance (P>0.05). Alternatively, expression was significantly higher in those with stages (P1-P3a) compared with P3b-P4a disease stages (66.6% vs. 37.1, P=0.03). Conclusion: Telomerase activity is increased in bilharzial bladder cancer although to a lesser degree than that reported for TCC in the western world, which could be explained, by different biological behavior or different assay methods. Further larger studies with more number of patients are still needed to determine its potential value for early detection and possible use as a therapeutic target.

Khaled, H. M., I. Abdel-Salam, M. Abdel-Gawad, A. Metwally, S. El-Demerdash, M. El-Didi, A. Morsi, and L. Ishak, "Evaluation of the BTA tests for the detection of bilharzial related bladder cancer: the Cairo experience.", European urology, vol. 39, issue 1, pp. 91-4, 2001 Jan. Abstract

OBJECTIVE: To evaluate the clinical performance of the BTA stat test and the BTA TRAK assay in the diagnosis of bilharzia-related bladder cancer and to calculate a new 'Egyptian' cut-off value for the BTA TRAK (quantitative) assay.

METHODS: Urine samples of 149 individuals were tested for the presence of the human complement factor H-related protein, the antigen detected by the BTA stat and BTA TRAK tests. The group consisted of 53 healthy volunteers, 20 patients with active bilharziasis, 11 patients with other urologic disorders including prostate cancer, and 65 patients with histologically proven bladder cancer. All samples were obtained prior to surgery or therapy.

RESULTS: The BTA stat test was positive in 64 of 65 samples from patients with bladder cancer, for an overall sensitivity of 99%. With a BTA TRAK assay cut-off of 60 U/ml (set at 97% specificity in the healthy population), the sensitivity of the TRAK assay was 94%. There was no statistically significant difference between the sensitivities of the two BTA tests in patients diagnosed with squamous cell carcinoma and those with transitional cell carcinoma. The overall specificity of the BTA stat test was 67% ranging from 15% in patients with bilharziasis to 94% in healthy volunteers. The overall specificity of the TRAK assay was 66%, again with negative results in 15% of the patients with bilharziasis.

CONCLUSIONS: The BTA stat test and TRAK tests are extremely sensitive in the detection of bladder cancer in the Egyptian population. Positive results (85%) are also observed in patients with active bilharziasis, which often leads to bladder cancer. Longitudinal follow-up of these positive cases is needed to determine whether these positive results are false or predictive of bladder cancer.

Khaled, H. M., I. Abdel-Salam, M. Abdel-Gawad, A. Metwally, S. El-Demerdash, M. El-Didi, A. Morsi, and L. Ishak, "Evaluation of the BTA tests for the detection of bilharzial related bladder cancer: the Cairo experience.", European urology, vol. 39, issue 1, pp. 91-4, 2001 Jan. Abstract

OBJECTIVE: To evaluate the clinical performance of the BTA stat test and the BTA TRAK assay in the diagnosis of bilharzia-related bladder cancer and to calculate a new 'Egyptian' cut-off value for the BTA TRAK (quantitative) assay.

METHODS: Urine samples of 149 individuals were tested for the presence of the human complement factor H-related protein, the antigen detected by the BTA stat and BTA TRAK tests. The group consisted of 53 healthy volunteers, 20 patients with active bilharziasis, 11 patients with other urologic disorders including prostate cancer, and 65 patients with histologically proven bladder cancer. All samples were obtained prior to surgery or therapy.

RESULTS: The BTA stat test was positive in 64 of 65 samples from patients with bladder cancer, for an overall sensitivity of 99%. With a BTA TRAK assay cut-off of 60 U/ml (set at 97% specificity in the healthy population), the sensitivity of the TRAK assay was 94%. There was no statistically significant difference between the sensitivities of the two BTA tests in patients diagnosed with squamous cell carcinoma and those with transitional cell carcinoma. The overall specificity of the BTA stat test was 67% ranging from 15% in patients with bilharziasis to 94% in healthy volunteers. The overall specificity of the TRAK assay was 66%, again with negative results in 15% of the patients with bilharziasis.

CONCLUSIONS: The BTA stat test and TRAK tests are extremely sensitive in the detection of bladder cancer in the Egyptian population. Positive results (85%) are also observed in patients with active bilharziasis, which often leads to bladder cancer. Longitudinal follow-up of these positive cases is needed to determine whether these positive results are false or predictive of bladder cancer.

el-Mawla, N. G., M. N. el-Bolkainy, and H. M. Khaled, "Bladder cancer in Africa: update.", Seminars in oncology, vol. 28, issue 2, pp. 174-8, 2001 Apr. Abstract

Carcinoma of the bladder is the most prevalent cancer in Egypt and in most African countries. At the National Cancer Institute (NCI), Cairo, it constitutes 30.3% of all cancers. The median age at diagnosis is 46 years, with a male preponderance of 5:1. Whether in Egypt or other African countries such as Sudan, Kenya, Uganda, Gold Coast, and Senegal, it is mostly of the squamous cell type, and arises in a background of schistosomiasis or bilharziasis. Tumors are usually advanced at the time of presentation. Bladder carcinogenesis is probably related to bacterial and human papilloma virus (HPV) infections, usually associated with bilharzial infestation. Management is mainly surgery, with 5-year survival rates after radical cystectomy increasing from 35% in the 1970s to 48% in the 1990s. The addition of adjuvant and neoadjuvant radiotherapy and chemotherapy to surgery since 1976 significantly improved both disease-free and overall survival rates. Molecular genetic studies concerning potential prognostic markers, tumorigenesis, and tumor progression in bilharzial bladder cancer are limited. However, a comprehensive detailed analysis of these factors is underway. Bilharzial bladder cancer is a preventable malignant disease. Primary prevention could be possible if the parasite is eliminated nationwide. Chemoprevention using retinoids or cyclooxygenase 2 (COX-2) inhibitors is a possible alternative. Semin Oncol 28:174-178.

el-Mawla, N. G., M. N. el-Bolkainy, and H. M. Khaled, "Bladder cancer in Africa: update.", Seminars in oncology, vol. 28, issue 2, pp. 174-8, 2001 Apr. Abstract

Carcinoma of the bladder is the most prevalent cancer in Egypt and in most African countries. At the National Cancer Institute (NCI), Cairo, it constitutes 30.3% of all cancers. The median age at diagnosis is 46 years, with a male preponderance of 5:1. Whether in Egypt or other African countries such as Sudan, Kenya, Uganda, Gold Coast, and Senegal, it is mostly of the squamous cell type, and arises in a background of schistosomiasis or bilharziasis. Tumors are usually advanced at the time of presentation. Bladder carcinogenesis is probably related to bacterial and human papilloma virus (HPV) infections, usually associated with bilharzial infestation. Management is mainly surgery, with 5-year survival rates after radical cystectomy increasing from 35% in the 1970s to 48% in the 1990s. The addition of adjuvant and neoadjuvant radiotherapy and chemotherapy to surgery since 1976 significantly improved both disease-free and overall survival rates. Molecular genetic studies concerning potential prognostic markers, tumorigenesis, and tumor progression in bilharzial bladder cancer are limited. However, a comprehensive detailed analysis of these factors is underway. Bilharzial bladder cancer is a preventable malignant disease. Primary prevention could be possible if the parasite is eliminated nationwide. Chemoprevention using retinoids or cyclooxygenase 2 (COX-2) inhibitors is a possible alternative. Semin Oncol 28:174-178.

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