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Book
Khaled, H. M., "Breast cancer at diagnosis in women of Africa and the Middle East", Breast Cancer in Women of African Descent: Springer Netherlands, pp. 81-90, 2006. AbstractWebsite

The myth behind the aetiology and efforts towards treatment and prevention of breast cancer were always present since antiquity. Two Egyptian papyruses, written approximately 1600 B.C. are concerned with the disease, the Edwin Smith Papyrus and the Ebers Papyrus. The first includes a case (no. 45) of bulging tumour of the breast recorded in lines 9 to 20 of the reproduction: If thou examinest a man having bulging tumours on his breast, (and) thou findest that (swellings) have spread over the breast; if thou puttest thy hand upon his breast upon these tumours, (and) thou findest them very cool, there being no fever at all therein when thy hand touches him, they have no granulation, they form no fluid, and they are bulging to thy hand, thou should say concerning him one having bulging tumours. An ailment with which I will attend. There is no (treatment). © 2006 Springer.

Journal Article
Khaled, H. M., "Acknowledgment of Referees", Journal of Advanced Research, vol. 1, no. 4, pp. I-II, 2010. AbstractWebsite
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Richards, M. A., R. E. Coleman, R. Hamsa, H. Khaled, M. Gad El Mawla, I. Kadry, A. Hablas, M. Ramadan, D. Allen, D. Y. Wang, et al., "Advanced breast cancer in Egyptian women: Clinical features and response to endocrine therapy. The Anglo-Egyptian Health Agreement Collaborative Study", European Journal of Surgical Oncology, vol. 18, no. 3, pp. 219-223, 1992. AbstractWebsite

Response to endocrine therapy and its relationship to the clinical features of the disease were studied in 84 Egyptian patients with inoperable locally advanced or metastatic breast cancer. Twenty-four premenopausal patients were treated by oophorectomy with or without concurrent prednisolone. Only one of 20 evaluable patients achieved an objective response. Median time to progression for premenopausal patients was 3 months. Sixty postmenopausal patients received tamoxifen 10 mg twice daily either alone or with prednisolone. Fourteen of 57 (25%) evaluable patients achieved an objective response (four complete remission, 10 partial remission). Median duration of response was 13 months and median time to progression for all postmenopausal patients was 5 months (range 1-30 months). The outcome for postmenopausal patients was similar to that found in a parallel study at Guy's Hospital, London. The response rate for premenopausal Egyptian patients was, however, disappointing and lends support to the claim that breast cancer in Egyptian women is particularly aggressive.

Amr, S. a, R. a Dawson, D. A. c Saleh, L. S. a Magder, N. N. e Mikhail, D. M. S. a George, K. b Squibb, H. d Khaled, and C. A. f Loffredo, "Agricultural workers and urinary bladder cancer risk in egypt", Archives of Environmental and Occupational Health, vol. 69, no. 1: Taylor and Francis Inc., pp. 3-10, 2014. AbstractWebsite

The authors examined the associations between farming and the risk for squamous cell (SCC) or urothelial cell (UC) carcinoma of the urinary bladder among Egyptians. The authors used data from a multicenter case-control study (1,525 male and 315 female cases, and 2,069 male and 547 female age- and residence-matched, population-based controls) to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs). Men in farming and who never smoked had increased risk for either SCC or UC (AOR [95% CI]: 4.65 [2.59-8.36] and 6.22 [3.82-10.15], respectively). If they ever smoked, their risks were 2.27 (1.75-2.95) and 1.93 (1.58-2.35), respectively. Women in farmer households were at increased risk for SCC (1.40 [0.93-2.09] and UC [1.25 (0.82-1.89]), although not statistically significant. Occupational and environmental exposures to farming increased the risk for bladder cancer among Egyptians. © 2014 Taylor & Francis Group, LLC.

Zekri, A. R., A. A. Bahnassi, B. Bove, Y. Huang, I. H. Russo, A. Rogatko, S. Shaarawy, O. A. Shawki, M. R. Hamza, S. Omer, et al., "Allelic instability as a predictor of survival in Egyptian breast cancer patients.", International journal of oncology, vol. 15, issue 4, pp. 757-67, 1999 Oct. Abstract

This work was designed with the purpose of determining whether the presence of allelic imbalances (AI) such as microsatellite instability (MSI) and loss of heterozygosity (LOH) in chromosomes 2, 11, 13, and 17 in primary breast cancer could be used as prognostic indicators of patient survival. The DNA from breast cancers removed from 29 patients who were followed-up for up to five years was analyzed for MSI and LOH using a panel of 24 markers located at chromosome 2 (TPO, D2S131, D2S144, D2S171, D2S177, D2S119, D2S123, D2S147 and D2S136), chromosome 11 (C-RAS, Int-2, D11S940, D11S912), chromosome 13 (D13S289, D13S260, D13S267, D13S218, D13S263, D13S155, and D13S162), and chromosome 17 (D17S513, TP53, D17S855, and D17S785). The frequency of AI in the markers studied ranged from 30-55%, being highest for D11S912, D2S171, TP53 and D17S855. Univariate analysis showed association between overall survival rate and AI in 9 out of the 24 markers tested. Five of them were located at the area of the mismatch repair gene (MMR)-2 gene, two at 11p, one at 13q and one at 17p. Using multivariate analysis, it was observed that only pathological and clinical stage (defined as stage II or not) and AI at D2S171, D11S912, or D17STP53 generated significant predictive models for survival.

Zekri, A. R., A. A. Bahnassi, B. Bove, Y. Huang, I. H. Russo, A. Rogatko, S. Shaarawy, O. A. Shawki, M. R. Hamza, S. Omer, et al., "Allelic instability as a predictor of survival in Egyptian breast cancer patients.", International journal of oncology, vol. 15, no. 4, pp. 757-767, 1999. AbstractWebsite

This work was designed with the purpose of determining whether the presence of allelic imbalances (AI) such as microsatellite instability (MSI) and loss of heterozygosity (LOH) in chromosomes 2, 11, 13, and 17 in primary breast cancer could be used as prognostic indicators of patient survival. The DNA from breast cancers removed from 29 patients who were followed-up for up to five years was analyzed for MSI and LOH using a panel of 24 markers located at chromosome 2 (TPO, D2S131, D2S144, D2S171, D2S177, D2S119, D2S123, D2S147 and D2S136), chromosome 11 (C-RAS, Int-2, D11S940, D11S912), chromosome 13 (D13S289, D13S260, D13S267, D13S218, D13S263, D13S155, and D13S162), and chromosome 17 (D17S513, TP53, D17S855, and D17S785). The frequency of AI in the markers studied ranged from 30-55%, being highest for D11S912, D2S171, TP53 and D17S855. Univariate analysis showed association between overall survival rate and AI in 9 out of the 24 markers tested. Five of them were located at the area of the mismatch repair gene (MMR)-2 gene, two at 11p, one at 13q and one at 17p. Using multivariate analysis, it was observed that only pathological and clinical stage (defined as stage II or not) and AI at D2S171, D11S912, or D17STP53 generated significant predictive models for survival.

Osman, I. A., H. I. a Scher, Z. - F. a Zhang, I. a Pellicer, R. b Hamza, S. b Eissa, H. b Khaled, and C. a c Cordon-Cardo, "Alterations affecting the p53 control pathway in bilharzial-related bladder cancer", Clinical Cancer Research, vol. 3, no. 4, pp. 531-536, 1997. AbstractWebsite

Bilharzial-related bladder carcinoma (BBC) is the most common malignant neoplasm in Egypt, also occurring with a high incidence in other regions of the Middle East and East Africa. The clinical and pathological features of BBC are different than those described for the conventional transitional cell carcinoma of the bladder, including the high incidence of squamous cell carcinoma reported in BBC and the fact that over 90% of BBC cases at presentation are advanced-stage tumors (P3 and P4). This study was conducted to better define the phenotypic alterations associated with BBC affecting the p53 cell cycle control pathway, including altered patterns of expression of downstream effect or proteins such as mdm2 and p21/WAF1. A well-characterized cohort of 125 patients affected with bilharzial-related bladder tumors was studied. Tumors were classified as squamous carcinomas (n = 68), transitional cell carcinomas (n = 55), or adenocarcinomas (n = 2). The products encoded by TP53, mdm2, and p21/WAF1 genes were analyzed by immunohistochemistry. Furthermore, the patterns of expression of these molecules were correlated with the Ki67 proliferative index. In addition, the microanatomical distribution of programmed cell death was assessed in a subset of tumors, using the so-called terminal deoxynucleotidyl transferase-mediated nick end labeling method. p53 nuclear overexpression was identified in 25 (20%) of 125 cases. Nuclear overexpression of mdm2 was detected in 74 (59.2%) of 125 cases. There was a statistically significant association between coexpression of both p53 and mdm2 and detection of lymph node metastases (P = 0.04). p21/WAF1 expression was detected in 87 (72%) of 121 evaluable cases. A high Ki67 proliferative index was observed in 99 (86%) of 115 evaluable cases. There was a statistically significant association between high Ki67 proliferative index and mdm2-positive phenotype (P = 0.005) and deep muscle invasion (P3b; P = 0.026) as well as lymph node metastases (P = 0.039). Apoptosis was observed in terminally differentiated tumor cells identified in the superficial layers of well-differentiated squamous carcinoma or exfoliating cells in transitional lesions. However, only rare apoptotic tumor cells were found in basal or suprabasal layers as well as in the invasive elements of the neoplasms studied. These results suggest that the frequency of p53 nuclear overexpression in BBC is lower than that reported for conventional transitional cell carcinoma. Nevertheless, tumors with p53 alterations have a greater propensity to progress. The prominent number of cases displaying an mdm2-positive phenotype suggests that this may be an early incident in BBC and should be regarded as a potential oncogenic phenomenon. This is supported by the significant correlation between high Ki67 proliferative index and mdm2 overexpression. The association of an aggressive clinical course with the coexpression of both p53 and mdm2 products might be viewed as a cooperative effect that develops in tumor progression.

g Zekri, A. - R. N. a, A. A. c Bahnassy, M. A. Hafez, A. M. R. f El-Shehaby, G. M. d Sherif, H. M. e Khaled, and N. b Zakhary, "Alterations of the fragile histidine triad gene in hepatitis C virus-associated hepatocellular carcinoma", Journal of Gastroenterology and Hepatology (Australia), vol. 20, no. 1, pp. 87-94, 2005. AbstractWebsite

Background and Aim: The present study was conducted to address whether homozygous deletion (HZD) or transcriptional alterations of the fragile histidine triad (FHIT) gene play a role in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCC). Methods: Homozygous deletion of the FHIT gene at exons 3-9 was assessed as well as mRNA FHIT expression using reverse transcription polymerase chain reaction. The study included 23 samples of HCC, 11 on top of cirrhosis and 12 non-cirrhotic, in addition to five cases with chronic active hepatitis (CAH), as well as seven morphologically normal tissues distant to the tumor (NDT) and 10 normal liver samples from liver transplantation donors. Results: Homozygous deletion was found in 18 of 23 HCC cases. The highest incidence of deletion was detected in exon 9 (52.0%) and the lowest in exon 7 (4.3%). Ten of the 18 cases (55.5%) showed deletion in more than one exon, eight in two exons, one in three exons and one in five exons. There was a significant association between HZD of exons 5 and 9 and HCC arising on top of cirrhosis (P = 0.041 and 0.006, respectively) as well as between exons 8 and 9 and the presence of CAH (P = 0.029 and 0.034, respectively). Aberrant FHIT transcripts were detected in 15 HCC cases (65.2%), 13 of them showed complete reduction of the mRNA transcripts and two showed abnormal bands. Sequence analysis of abnormal-sized transcripts revealed that they were generated by the fusion of exons 5 and 7 as well as exons 7 and 9. In contrast, six of the seven NDT samples tested (85.6%) showed HZD in one or more exons. None of the normal liver samples from liver transplantation donors showed any changes. The highest incidence of HZD was detected in exon 9 (five of six cases representing 83.3%) and the lowest was in exon 4 (one of six cases representing 16.7%). Four cases showed the same aberrant FHIT HZD in both NDT and matched HCC. Conclusions: The results of the present study indicate that the FHIT gene is a frequent target in hepatitis C virus-associated HCC and that alterations affecting this gene could be an early event in this type of neoplasm as they were detected in cirrhotic and CAH patients. However, this should be confirmed by a larger, extended study including more cases of cirrhotic and CAH patients as well as matched tumor and normal samples. © 2005 Blackwell Publishing Asia Pty Ltd.

g Zekri, A. - R. N. a, A. A. c Bahnassy, M. A. Hafez, A. M. R. f El-Shehaby, G. M. d Sherif, H. M. e Khaled, and N. b Zakhary, "Alterations of the fragile histidine triad gene in hepatitis C virus-associated hepatocellular carcinoma", Journal of Gastroenterology and Hepatology (Australia), vol. 20, no. 1, pp. 87-94, 2005. AbstractWebsite

Background and Aim: The present study was conducted to address whether homozygous deletion (HZD) or transcriptional alterations of the fragile histidine triad (FHIT) gene play a role in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCC). Methods: Homozygous deletion of the FHIT gene at exons 3-9 was assessed as well as mRNA FHIT expression using reverse transcription polymerase chain reaction. The study included 23 samples of HCC, 11 on top of cirrhosis and 12 non-cirrhotic, in addition to five cases with chronic active hepatitis (CAH), as well as seven morphologically normal tissues distant to the tumor (NDT) and 10 normal liver samples from liver transplantation donors. Results: Homozygous deletion was found in 18 of 23 HCC cases. The highest incidence of deletion was detected in exon 9 (52.0%) and the lowest in exon 7 (4.3%). Ten of the 18 cases (55.5%) showed deletion in more than one exon, eight in two exons, one in three exons and one in five exons. There was a significant association between HZD of exons 5 and 9 and HCC arising on top of cirrhosis (P = 0.041 and 0.006, respectively) as well as between exons 8 and 9 and the presence of CAH (P = 0.029 and 0.034, respectively). Aberrant FHIT transcripts were detected in 15 HCC cases (65.2%), 13 of them showed complete reduction of the mRNA transcripts and two showed abnormal bands. Sequence analysis of abnormal-sized transcripts revealed that they were generated by the fusion of exons 5 and 7 as well as exons 7 and 9. In contrast, six of the seven NDT samples tested (85.6%) showed HZD in one or more exons. None of the normal liver samples from liver transplantation donors showed any changes. The highest incidence of HZD was detected in exon 9 (five of six cases representing 83.3%) and the lowest was in exon 4 (one of six cases representing 16.7%). Four cases showed the same aberrant FHIT HZD in both NDT and matched HCC. Conclusions: The results of the present study indicate that the FHIT gene is a frequent target in hepatitis C virus-associated HCC and that alterations affecting this gene could be an early event in this type of neoplasm as they were detected in cirrhotic and CAH patients. However, this should be confirmed by a larger, extended study including more cases of cirrhotic and CAH patients as well as matched tumor and normal samples. © 2005 Blackwell Publishing Asia Pty Ltd.

Zekri, A. - R. N., A. A. Bahnassy, M. Hafez, A. M. El-Shehaby, G. M. Sherif, H. M. Khaled, and N. Zakhary, "Alterations of the fragile histidine triad gene in hepatitis C virus-associated hepatocellular carcinoma.", Journal of gastroenterology and hepatology, vol. 20, issue 1, pp. 87-94, 2005 Jan. Abstract

BACKGROUND AND AIM: The present study was conducted to address whether homozygous deletion (HZD) or transcriptional alterations of the fragile histidine triad (FHIT) gene play a role in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCC).

METHODS: Homozygous deletion of the FHIT gene at exons 3-9 was assessed as well as mRNA FHIT expression using reverse transcription polymerase chain reaction. The study included 23 samples of HCC, 11 on top of cirrhosis and 12 non-cirrhotic, in addition to five cases with chronic active hepatitis (CAH), as well as seven morphologically normal tissues distant to the tumor (NDT) and 10 normal liver samples from liver transplantation donors.

RESULTS: Homozygous deletion was found in 18 of 23 HCC cases. The highest incidence of deletion was detected in exon 9 (52.0%) and the lowest in exon 7 (4.3%). Ten of the 18 cases (55.5%) showed deletion in more than one exon, eight in two exons, one in three exons and one in five exons. There was a significant association between HZD of exons 5 and 9 and HCC arising on top of cirrhosis (P = 0.041 and 0.006, respectively) as well as between exons 8 and 9 and the presence of CAH (P = 0.029 and 0.034, respectively). Aberrant FHIT transcripts were detected in 15 HCC cases (65.2%), 13 of them showed complete reduction of the mRNA transcripts and two showed abnormal bands. Sequence analysis of abnormal-sized transcripts revealed that they were generated by the fusion of exons 5 and 7 as well as exons 7 and 9. In contrast, six of the seven NDT samples tested (85.6%) showed HZD in one or more exons. None of the normal liver samples from liver transplantation donors showed any changes. The highest incidence of HZD was detected in exon 9 (five of six cases representing 83.3%) and the lowest was in exon 4 (one of six cases representing 16.7%). Four cases showed the same aberrant FHIT HZD in both NDT and matched HCC.

CONCLUSIONS: The results of the present study indicate that the FHIT gene is a frequent target in hepatitis C virus-associated HCC and that alterations affecting this gene could be an early event in this type of neoplasm as they were detected in cirrhotic and CAH patients. However, this should be confirmed by a larger, extended study including more cases of cirrhotic and CAH patients as well as matched tumor and normal samples.

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.

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.

El Sharkawi, F. Z. a, H. A. b El Shemy, and H. c Khaled, "Anticancer activity of some commercial antihypertensive drugs by Neutral Red assay", Life Science Journal, vol. 10, no. 1, pp. 609-613, 2013. AbstractWebsite

Lisinopril, propranolol and nifedipine are three commercial drugs used clinically for the management of hypertension, angina pectoris, and cardiac arrhythmias. It has been reported that these drugs have inhibitory effects on some cancer cells. In the current study the cytotoxicity of these drugs was evaluated against HeLa, HepG2, MCF- 7 and EACC transformed cell lines using Neutral Red and Trypan Blue assay methods. The three drugs showed a cytotoxicity against HeLa, HepG2 and MCF-7 cells with different potentiality. Lisinopril was the most potent cytotoxic drug against HepG2 cells with IC50 = 33.8±88.4 μg/ml at the concentration of 300ug/ml; while Nifedipine was the most active one against HeLa cells with IC50 =130±58.4ug/ml at a concentration of 300ug/ml. Propranolol was the most active against MCF7 cells IC50 of 78.0± 121.4 μg/ml at a concentration of 3000ug/ml. The three used drugs inhibited the growth of EACC cells and propranolol showed highest inhibitory activity; it inhibited 97.7% of cell growth at a concentration of 300 ug/ml and 100% inhibition at a concentration of 3000 ug/ml. Lisinopril and nifedipine showed a lower rate of growth inhibition of 18.28% and 11.40% respectively at a concentration of 3000ug/ml. In conclusion: At these high concentrations, the three tested drugs are lethal in vitro to cancer cells of endometrial, cervical, hepatic, and breast origin. Further animal studies are required to confirm this conclusion.

Wolpert, B. J. a, S. a Amr, D. A. b Saleh, S. c Ezzat, I. d Gouda, I. d Loay, T. e Hifnawy, M. f Abdel-Hamid, N. N. g Mikhail, M. a Zhan, et al., "Associations differ by sex for catechol-O-methyltransferase genotypes and bladder cancer risk in South Egypt", Urologic Oncology: Seminars and Original Investigations, vol. 30, no. 6, pp. 841-847, 2012. AbstractWebsite

Objectives:To examine associations between urinary bladder cancer risk and polymorphisms of the gene encoding the catechol estrogen-metabolizing enzyme, catechol-O-methyltransferase (COMT), among Egyptian women and men. Materials and methods:We used questionnaire and genotype data from a case-control study in Egypt. This analysis focused on South Egypt cases with confirmed urothelial (UC) or squamous cell (SCC) carcinoma of the bladder, and controls frequency-matched on sex, 5-year age-group, and residence governorate. Real-time PCR on blood specimen DNA was used to determine COMT genotypes encoding for Val/Val, Val/Met, and Met/Met, the enzyme forms associated with high, intermediate, or low activity, respectively. ResultsThe study sample, which included 255 women and 666 men, consisted of 394 cases with histologically confirmed UC (225) or SCC (n = 169), and 527 controls. The odds of having either type of bladder cancer were lower among men with genotypes encoding Val/Met or Met/Met than among those with the genotype encoding Val/Val, even after adjustment for other factors, such as smoking and schistosomiasis history [adjusted odds ratio (AOR): 0.64; 95% confidence interval (CI): 0.43, 0.96]; however, the association was statistically significant for SCC (AOR 0.57; 95% CI: 0.34, 0.96) but marginal for UC (AOR: 0.64; 95% CI: 0.39, 1.02). No significant associations were detected between bladder cancer risk and COMT genotypes among postmenopausal women.: Conclusions:These findings suggest that even after controlling for established risk factors, the involvement of COMT genotypes in bladder cancer risk differs among men compared with women in South Egypt. © 2012.

El-Sharkawi, F. a, M. b El Sabah, Z. A. Hassan, and H. c Khaled, "The biochemical value of urinary metalloproteinases 3 and 9 in diagnosis and prognosis of bladder cancer in Egypt", Journal of Biomedical Science, vol. 21, no. 1: BioMed Central Ltd., 2014. AbstractWebsite

Background: Matrix metalloproteinases (MMPs) have long been associated with cancer-cell invasion and metastasis. Few studies are available that describe this association with bladder cancer either related or unrelated to schistosoma infection. Evaluating the urinary levels of MMP3 and MMP9 as diagnostic and prognostic biomarkers in different stages of schistosomal and non schistosomal bladder cancer was the aim of the present study. Urine samples were collected from 70 patients with schistosomal and non schistosomal bladder cancer at early and advanced stages and also from12 healthy volunteers as controls. Urinary levels of MMP-3 and MMP-9 was measured by ELISA technique. Sensitivity and specificity of both markers were determined. Results: Urinary levels of both MMP-3 and MMP-9 were significantly elevated in all bladder cancer patients compared with controls. MMP-3 started to elevate in early stages of schistosomal bladder cancer (0.173 ng/ml) and non-schistosomal bladder cancer patients (0.308 ng/ml) compared to control (0.016 ng/ml) and remained elevated in advanced stages (0.166, 0.235 ng/ml) of both types of bladder cancer patients. In contrast, MMP-9 showed a significant elevation in advanced stages only of both schistosomal and non schistosomal bladder cancer patients (10.33, 21.22 ng/ml) compared to control (0.409 ng/ml) and this elevation of both markers was much higher in non schistosomal bladder cancer. Both Metalloproteinases were specific for the diagnosis of the disease but MMP-3 was more sensitive and this sensitivity was evident in the early stage (84.85% for MMP3, 27.28% for MMP9). Conclusions: MMP3 may be the recommended urinary metalloproteinases as early diagnostic biomarker in the early stages of both types of bladder cancer although both MMP9 and MMP3 can be used in the diagnosis of advanced stages. Further studies are required on large number of urine samples to confirm these results.

Khaled, H. M., "Bladder cancer and bilharziasis today", Cancer Journal, vol. 6, no. 2, pp. 65-71, 1993. AbstractWebsite
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b El Mawla, N. G. a, M. N. a El Bolkainy, and H. M. a Khaled, "Bladder cancer in Africa: Update", Seminars in Oncology, vol. 28, no. 2, pp. 174-178, 2001. AbstractWebsite

Carcinoma of the bladder is the most prevalent cancer in Egypt and in most African countries. At the National Cancer Institute (NCl), 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. Copyright © 2001 by W.B. Saunders Company.

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.

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.

Yip, C. - H. a, E. b Cazap, B. O. c d Anderson, K. L. e Bright, M. f Caleffi, F. g h Cardoso, A. M. i Elzawawy, J. B. j Harford, G. D. k l Krygier, S. m Masood, et al., "Breast cancer management in middle-resource countries (MRCs): Consensus statement from the Breast Health Global Initiative", Breast, vol. 20, no. SUPPL. 2, pp. S12-S19, 2011. AbstractWebsite

In middle resource countries (MRCs), cancer control programs are becoming a priority as the pattern of disease shifts from infectious diseases to non-communicable diseases such as breast cancer, the most common cancer among women in MRCs. The Middle Resource Scenarios Working Group of the BHGI 2010 Global Summit met to identify common issues and obstacles to breast cancer detection, diagnosis and treatment in MRCs. They concluded that breast cancer early detection programs continue to be important, should include clinical breast examination (CBE) with or without mammography, and should be coupled with active awareness programs. Mammographic screening is usually opportunistic and early detection programs are often hampered by logistical and financial problems, as well as socio-cultural barriers, despite improved public educational efforts. Although multidisciplinary services for treatment are available, geographical and economic limitations to these services can lead to an inequity in health care access. Without adequate health insurance coverage, limited personal finances can be a significant barrier to care for many patients. Despite the improved availability of services (surgery, pathology, radiology and radiotherapy), quality assurance programs remain a challenge. Better access to anticancer drugs is needed to improve outcomes, as are rehabilitation programs for survivors. Focused and sustained government health care financing in MRCs is needed to improve early detection and treatment of breast cancer. © 2011 Elsevier Ltd.

Moneer, M. a, M. b El-Didi, and H. c Khaled, "Breast conservative surgery: Is it appropriate for locally advanced breast cancer following downstaging by neoadjuvant chemotherapy? A pathological assessment", Breast, vol. 8, no. 6, pp. 315-319, 1999. AbstractWebsite

The application of breast conserving surgery to down-staged cases with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NACT) is still a controversial issue with a variable incidence of locoregional failures. In this study, the response of LABC to NACT was assessed pathologically and the elegible candidates for breast conserving surgery were identified retrospectively. The efficacy of preoperative clinical examination and mammography in detecting these pathological changes were also evaluated. The study included 41 LABC cases. They received NACT (FAC) and were then subjected to a mastectomy. The cases were examined clinically and by mammography before starting treatment and immediately before surgery. Residual tumours in the mastectomy specimens were correlated with the pretreatment and preoperative clinical and mammographic findings inorder to assess the efficacy of these tools for detection of NACT-induced changes. After 3 cycles of NACT, 78% of women showed an objective response. However, only 25% of them would have been eligible for breast conserving surgery. The remaining responders had an increased incidence of either multifocality and or peritumoural in situ carcinoma. Both clinical examination and mammography were inadequate for detection of these chemotherapy-induced changes and hence for selecting suitable candidates for breast conservation. This study has shown that tumour regression by NACT is probably induced by a process of tumour segmentation and is associated with an increased incidence of ductal in situ lesions in the original tumour bearing area. (C) 1999 Harcourt Publishers Ltd.

Moneer, M. a, M. b El-Didi, and H. c Khaled, "Breast conservative surgery: Is it appropriate for locally advanced breast cancer following downstaging by neoadjuvant chemotherapy? A pathological assessment", Breast, vol. 8, no. 6, pp. 315-319, 1999. AbstractWebsite

The application of breast conserving surgery to down-staged cases with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NACT) is still a controversial issue with a variable incidence of locoregional failures. In this study, the response of LABC to NACT was assessed pathologically and the elegible candidates for breast conserving surgery were identified retrospectively. The efficacy of preoperative clinical examination and mammography in detecting these pathological changes were also evaluated. The study included 41 LABC cases. They received NACT (FAC) and were then subjected to a mastectomy. The cases were examined clinically and by mammography before starting treatment and immediately before surgery. Residual tumours in the mastectomy specimens were correlated with the pretreatment and preoperative clinical and mammographic findings inorder to assess the efficacy of these tools for detection of NACT-induced changes. After 3 cycles of NACT, 78% of women showed an objective response. However, only 25% of them would have been eligible for breast conserving surgery. The remaining responders had an increased incidence of either multifocality and or peritumoural in situ carcinoma. Both clinical examination and mammography were inadequate for detection of these chemotherapy-induced changes and hence for selecting suitable candidates for breast conservation. This study has shown that tumour regression by NACT is probably induced by a process of tumour segmentation and is associated with an increased incidence of ductal in situ lesions in the original tumour bearing area. (C) 1999 Harcourt Publishers Ltd.

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.

Anwar, W. A. a, H. M. b Khaled, H. A. c Amra, H. d El-Nezami, and C. A. e Loffredo, "Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: Possibilities for prevention", Mutation Research - Reviews in Mutation Research, vol. 659, no. 1-2, pp. 176-184, 2008. AbstractWebsite

The burden of hepatocellular carcinoma (HCC) has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. This has been attributed to several biological (e.g. hepatitis B and C virus infection) and environmental factors (e.g. aflatoxin, AF). Other factors such as cigarette smoking, occupational exposure to chemicals such as pesticides, and endemic infections in the community, such as schistosomiasis, may have additional roles in the etiology or progression of the disease. Estimates of the burden of cancer caused by these factors provide an opportunity for prevention. Previously, there was strong evidence that hepatitis B virus (HBV) was the major cause of HCC in Egypt, but more recently HCV has become the predominant factor associated with the more recent epidemic of HCC. It has been well documented that Egypt has one of the highest prevalence rates of HCV infection in the world. The natural history of HCV infection and disease progression, however, are influenced by additional factors such as duration of infection, age at infection, sex, co-infection with HBV, the level of HCV viraemia and its genotype. The role of exposure to aflatoxins and development of HCC in Egypt was historically less clear. Nevertheless, recent food sampling surveys and population-based studies indicated that exposure to aflatoxins in Egypt may have been underestimated in the past. Recent results indicated that both local and imported samples were positive for aflatoxin B1 (AFB1, 17.5% and 20%, respectively), with concentrations ranging from 3 to 25 μg/kg. The level of AFB1 was dependent on the area of collection as well as the season of the year. In a population-based study, the level and frequency of aflatoxin M1 (AFM1, a major metabolite of aflatoxin B1 excreted in breast milk) was assessed as a biomarker of maternal exposure. The samples were collected from a selected group of 388 Egyptian lactating mothers during May-September 2003. Non-working status, obesity, high corn oil consumption, and the number of offspring contributed to the variability in occurrence of AFM1 in breast milk. Prevention and intervention approaches directed to risk factors of HCC can play a critical role in its prevention. In the case of HCV infection a prevention programme can be achieved by changing personal behaviors and/or cultural habits which are risk factors for HCV transmission, such as injection with contaminated syringes, blood transfusion, surgical operations, venous catheterization, use of common syringes, dental treatment and circumcision at home. Prevention of exposure to aflatoxins can be achieved either at community (via good agriculture practices) or individual levels (treatment or dietary interventions). In conclusion, due to the alarming increase in the incidence of HCC in Egypt, there is a need to further investigate the contribution of these emerging risk factors to the development of HCC in Egypt. This may enable us to determine the susceptibility to HCC among high-risk groups and to provide these individuals with effective measures for early prevention or intervention. © 2008 Elsevier B.V. All rights reserved.

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