DNA copy number changes were investigated in 69 samples of schistosoma-associated (SA) and non-schistosoma-associated (NSA. squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC) of the ...bladder by comparative genomic hybridization (CGH). DNA copy number changes were detected in 47 tumors. SA tumors had more changes than NSA tumors (mean, 7
vs. 4), whereas the number of changes in SCC and TCC tumors was similar. SA tumors displayed more gains than losses (1.7:1), whereas NSA tumors showed an equal number of gains and losses. Changes that were observed at similar frequencies in SCC and TCC, irrespective of the schistosomal status, included gains and high-level amplifications at 1q, 8q, and 20q and losses in 9p and 13q. These changes may be involved in a common pathway for bladder tumor development and progression independent of schistosomal status or histological subtype. Losses in 3p and gains at 5p were seen only in SCC (
P < 0.01) and losses in 5q were more frequent in SA-SCC than in other tumors (
P < 0.05). However, changes that were more frequent in TCC than those in SCC included gains at 17q (
P < 0.01) and losses in 4q (
P < 0.05) and 6q (
P < 0.01). Gains and high-level amplifications at 5p were seen only in SA-SCC (
P < 0.01), whereas gains and high-level amplifications with minimal common overlapping regions at 11q13 were more frequently seen both in SA-SCC and SA-TCC tumors (
P < 0.01). In addition to the above mentioned alterations, several other changes were also seen at lower frequencies. The variations in the DNA copy number changes observed in TCC, SCC, SA, and NSA bladder carcinomas suggest that these tumors have different genetic pathways.
Egypt shows a parallel increase in premenopausal breast cancer and environmental pollution. The purpose of this study is to explore a possible relationship between oxidative DNA damage, urinary ...estrogen metabolites and breast cancer in Egyptian premenopausal women. We conducted a pilot study of Egyptian breast cancer involving 29 cases and 32 controls and analysed lymphocyte DNA levels of 7,8-dihydro-8-oxo-2′-deoxyguanine (8-oxo-dG), a measure of oxidative DNA damage using high performance liquid chromatography with electro-chemical detection (HPLC-ECD) method. We analysed levels of urinary estrogen metabolites, 2-hydroxyestrone (2-OHE) and 16α-hydroxyestrone (16α-OHE) by an enzyme immuno assay. We also collected residential, occupational, and reproductive histories of all study subjects. We detected, in all subjects, exceptionally high levels of 8-oxo-dG and thus oxidative DNA damage, the levels (mean 8-oxo-dG/10
5
dG ± SD) were significantly (P < 0.01) higher in breast cancer cases (139.4 ± 78.4) than in controls (60.9 ± 51.5). Urinary 2-OHE and 16α-OHE or their ratio was not significantly different between cases and controls. However, 8-oxo-dG levels were positively correlated (P < 0.05) with 2-OHE and 16α-OHE from cases while controls showed a negative correlation (P < 0.05). Urban residence (Odds Ratio OR 3.1; Confidence interval CI, 1.1 - 9.3), infertility (OR 9.8; CI 1.1 - 89.7), age (OR 2.6; CI 1.4 - 4.6) and 8-oxo-dG (OR 5.8; CI 1.9 - 17.5) levels were found to be significant predictors of breast cancer. Our finding of exceptionally high levels of 8-oxo-dG, a common result of oxidative DNA damage, warrant future studies on a larger population of premenopausal women in Egypt with consideration of other susceptibility markers and dietary characteristics.
The aim of this project was to study the kinetics of both Tl and Tc-99m MIBI in PBM by evaluating tumor to normal tissue ratio in early (E) images acquired within 1/2 hour and delayed (D) images ...acquired three hours following the i.v. injection of 3 mCi (111 MBq) of Tl and 20 mCi (740 MBq) of MIBI on 2 separate days in 49 patients. The washout index was calculated from E ratio minus D ratio divided by E ratio. A negative ratio indicating build up of activity in D images and a positive ratio indicated washout of activity from the E images. In addition, the findings were correlated with the following immunohistochemical parameters: pathological grading, number of cells in mitotic division (PCNA- Ki-67), angiogenesis (well formed and ill formed blood vessels) and presence or absence of Bcl 2 Oncogene (release antiapoptotic signals). Results showed that in all benign and malignant lesions, MIBI showed consistent washout varying from 19-27% while with Tl, there was persistent washout in all benign lesions and mixed washout or buildup varying from +16% to minus 17% in malignant lesions, (E) ratios showed a reasonable correlation between Tl and MIBI (r = 0.5). There was more significant correlation between the D ratios (r = 0.8). Due to high (E) MIBI uptake ratios and their higher percentage of washout than Tl, delayed ratios came close to each other. Immunohistochemical analysis revealed benign lesions presented with low mitotic rate: Ki-67 (71.4%), PCNA (14.2%), low amount of ill formed blood vessels (42.8%) and high amount well formed blood vessels (100%). While malignant lesions presented with high mitotic rate Ki-67 was (96.7%), PCNA (100%), high amount of ill formed blood vessels (73.3% in GII and 100% in Grade III) and less amount of well formed blood vessels of 90% and 83.4% in Grade II and III respectively. Bcl-2 was variable in both benign and malignant lesions with 71.4% in benign, 73.4% in GII and 16.7 in GIII malignancy. In conclusion, early uptake ratio in both benign and malignant tumors is related to the degree of angiogenesis, percentage of ill formed blood vessels, high mitotic activity reflected by high grade of tumor and high percentage of PCNA and Ki-67.
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 effector 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.
The present study was conducted to analyze the alterations affecting cyclins D1, E, and A in bilharzial bladder cancer and to assess their potential clinical significance. A total of 125 cases were ...examined. Histopathological subtypes included 68 squamous cell carcinomas, 55 transitional cell carcinomas, and 2 adenocarcinomas. Immunohistochemical analyses were performed using a panel of well-characterized antibodies. The results were correlated with proliferative index, as assessed by Ki67 antigen expression. The cyclin D1-positive phenotype, defined as the identification of positive immunoreactivity in the nuclei of >/=20% of tumor cells, was found in 33 of 107 (31%) evaluable cases. A significant association was observed between the cyclin D1-positive phenotype and deep muscle invasion (P = 0.02), high tumor grade (P = 0.02), and Ki67 high proliferative index (P = 0.03). The cyclin E-positive phenotype, defined as per cyclin D1, was found in 79 of 106 (75%) evaluable cases. The cyclin A-positive phenotype, defined using the above criteria, was identified in 60 of 108 (56%) evaluable cases. No statistically significant association was found between cyclins E or A and clinicopathological parameters or proliferative index. However, there was a strong association between the expression of cyclin D1 and the coexpression of cyclins A and/or E (P = 0.05). Ki67 proliferative index was considered high when >/=20% of tumor cells displayed positive nuclear staining, a phenotype that was observed in 99 of 115 (86%) cases. These data support the hypothesis that cyclin D1 activation determines the evolution of a particular subset of aggressive bladder tumors. In addition, cyclins E and A seem to follow an unscheduled pattern of expression, based on the high frequency of identifying a positive phenotype for these cyclins and the lack of correlation between their expression and Ki67 high proliferative index. It may be postulated that the expression of G1 cyclin genes is deregulated in bilharzial bladder cancer, and that cyclin D1 acts as an oncogenic event in these neoplasms. Moreover, the moderate number of tumors displaying the cyclin D1-positive phenotype (31%) versus the high frequency observed for both cyclins E (75%) and A (56%), suggests a short G1 disbalanced by a long S phase and a rapid transversal of the cell cycle, as evidenced by a high Ki67 index observed in 86% of these cases. This imbalance in the cell cycle, together with alterations reported on the p53 pathway, might underline the accumulation of DNA damage and the aggressive clinical course of bilharzial bladder cancer.
The purpose of this study was to examine the psychometric properties of Cognitive Emotion Regulation Questionnaire (Garnefski, Kraaij et al., 2002), using a sample of adolescents from Egypt, aged 13, ...14 and 15 years. The results indicate that the nine-factor model was successful, obtaining adequate fit indexes: χ2, df=381.3, χ2/df=5.5, CFI=.92, TLI=.92, RMSEA=.05 and GFI=.93. Model fit indices showed acceptable goodness of fit values for nine factors structure of 36 items of the scale. Standardized factor loadings for one factor structure of Cognitive Emotion Regulation Questionnaire have values between .39 and .75 and all t values are significant for all of the items. According to Spearman correlation analyses, there were significant positive correlations between the adaptive cognitive emotion regulation strategies and all factors of Wong and Law Emotional Intelligence Scale. However, negative correlations were noticed between the maladaptive cognitive emotion regulation strategies and all factors of Wong and Law Emotional Intelligence Scale. The test-retest reliability was acceptable. The test-retest coefficient for the total scale score was .92.
Colorectal cancers remain to be a common cause of cancer-related death. Early-onset cases as well as those of various ethnic origins have aggressive clinical features, the basis of which requires ...further exploration. The aim of this work was to examine the expression patterns of p15INK4b and SMAD4 in colorectal carcinoma of different ethnic origins. Fifty-five sporadic colorectal carcinoma of Egyptian origin, 25 of which were early onset, and 54 cancers of Finnish origin were immunohistochemically stained with antibodies against p15INK4b and SMAD4 proteins. Data were compared to the methylation status of the p15INK4b gene promotor. p15INK4b was totally lost or deficient (lost in ≥ 50% of tumor cell) in 47/55 (85%) tumors of Egyptian origin as compared to 6/50 (12%) tumors of Finnish origin (p=7e-15). In the Egyptian cases with p15INK4b loss and available p15INK4b promotor methylation status, 89% of cases which lost p15INK4b expression were associated with p15INK4b gene promotor hypermethylation. SMAD4 was lost or deficient in 25/54 (46%) tumors of Egyptian origin and 28/48 (58%) tumors of Finnish origin. 22/54 (41%) Egyptian tumors showed combined loss/deficiency of both p15INK4b and SMAD4, while p15INK4b was selectively lost/deficient with positive SMAD4 expression in 24/54 (44%) tumors. Loss of p15INK4b was associated with older age at presentation (>50 years) in the Egyptian tumors (p=0.04). These data show for the first time that p15INK4b loss of expression marks a subset of colorectal cancers and ethnic origin may play a role in this selection. In a substantial number of cases, the loss was independent of SMAD4 but rather associated with p15INK4b gene promotor hypermethylation and old age which could be related to different environmental exposures.
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