Mahmoud Mohamed El-Merzabani

HYPERTHERMIC POTENTIATION OF CISPLATIN CYTOTOXICITY ON SOLID EHRLICH CARCINOMA

Background Hyperthermia produces marked effects on many biochemical parameters of tumor cells and has been reported to potentiate the effect of many drugs. We therefore evaluated the possible synergistic effect between hyperthermia and cisplatin against solid Ehrlich carcinoma. The study was based on the measurement of some biologic characteristics in tumor tissues, namely: DNA, RNA, and protein content and their rate of synthesis as parameters for nuclear damage; total lipids and cholesterol as parameters for membrane damage; acid-phosphatase and acid-ribonuclease as parameters for lysosomal damage; and tumor volume as a direct parameter for tumor growth. Methods Treatment of solid Ehrlich carcinoma by hyperthermia at 43 °C for 30 min for 3 successive days produced a 41.5 % decrease in tumor volume, as well as a significant decrease in nucleic acids, protein contents and their rate of synthesis, in total lipids and cholesterol, and in acid-phosphatase and acid-ribonuclease. Chemotherapeutic management of the tumor by 5 mg/kg × 3 of cisplatin alone showed a continuous increase in tumor volume but at a lower rate than that of the untreated control. However, when cisplatin was given 1 h prior to hyperthermia, the tumor volume was significantly decreased by 82.6 %. Results The effects observed on all the investigated parameters were intensified when cisplatin was combined with hyperthermia. The results obtained suggest that hyperthermia may enhance the penetration of cisplatin to its target site inside the tumor cells due to a membrane-damaging effect. The enhanced lethality of cisplatin on tumor cells may also be due to the inhibition of DNA repair processes by hyperthermia.

A study on the aetiological factors of bilharzial bladder cancer in Egypt--1. Nitrosamines and their precursors in urine.

Abstract Endogenous nitrosamines and nitrosamines formed by deliberate chemical nitrosation of urine have been found to be much higher in urine of bilharzial infested and bladder cancer patients when compared with that of normal or cancer patients other than bladder cancer. Thiocyanate had been detected in all different types of urine samples. Nitrite was not found in normal urine but it had been detected in the urine of 3 out of 10 bilharzial patients. 7 out of 15 bladder cancer patients and 1 out of 14 non-bladder cancer patients.

Sensitization of TRAIL-induced apoptosis in human hepatocellular carcinoma HepG2 cells by phytochemicals.

AIMS The present study investigated and compared the potential chemosensitizing effect of indole-3-carbinol (I3C) and epigallocatechin-3-gallate (EGCG) on TRAIL-induced apoptosis in human hepatocellular carcinoma (HCC) HepG2 cells as well as the possible mechanisms underlying these modulatory effects, particularly their effects on TRAIL death receptors (DR), Bcl-2 and c-FLIP proteins expression. MAIN METHODS HepG2 cells were treated with different concentrations of TRAIL ranging from 3 to 400ng/ml for 24h. For studying the modulatory effects of the phytochemicals on TRAIL-induced apoptosis, I3C and EGCG were used at concentrations that inhibit only 5% of the cells which were found to be 110μM and 70μg/ml, respectively. KEY FINDINGS It was found that 24h pre-treatment of HepG2 cells with either 110μM I3C or 70μg/ml EGCG significantly enhanced TRAIL cytotoxicity. EGCG induced more reduction in IC50 of TRAIL compared to I3C. Nevertheless, I3C was more efficient than EGCG in enhancing TRAIL cytotoxicity at higher concentrations of TRAIL. Both I3C and EGCG significantly increased caspase-3 activity, DNA fragmentation percentage, DR4 and DR5 protein expression as well as decreased Bcl-2 protein expression when compared to control groups. SIGNIFICANCE Both I3C and EGCG chemosensitized HCC HepG2 cells to TRAIL-induced apoptosis. These modulatory effects were partially attributed to the up-regulation of caspase-3 activity and DR4 and DR5 expression, as well as down-regulation of Bcl-2 expression. Only EGCG was able to induce a significant decrease in c-FLIP expression level.

A study on the aetiological factors of bilharzial bladder cancer in Egypt. 3. Urinary β-glucuronidase

Human tissues and E. coli β-glucuronidase showed distinct differences in their properties with respect to substrate specificity, pH optima and effect of different agents. E. coli and pseudomonas sp. the most commonly occurring bacteria in the urine of bilharzial and bladder cancer patients showed markedly high levels of β-glucuronidase. Increased level of β-glucuronidase activity had been found in the urine of bilharzial and bladder cancer patients compared to that of normal urine. β-glucuronidase in urine showed two peaks of activity one was found to be of tissue origin and the other of bacterial origin, with optimal activity at pH 5.0 and 7.0 respectively. A positive correlation was clearly demonstrated between type and severity of bacterial infection and urinary β-glucuronidase level. The possible role of urinary β-glucuronidase in the aetiology of bilharzial bladder cancer had been discussed.

Bladder carcinogenesis using bilharzia-infested Swiss albino mice

Abstract Experimental studies were carried out on female Swiss albino mice to evaluate the possible role of: liver injury, urine inborn carcinogens and local irritation of bladder mucosa in the development of bilharzial bladder cancer. In mice, the liver and intestine are only involved by parasite, but the urinary bladder is spared. Mice with induced liver injury due to either: bilharzial infestation alone, hepatocarcinogens alone (2-naphthylamine (2-NA) or 2-acetylaminofluorene (2-AAF)), or both together, did not develop bladder tumors. Also, mice receiving 1% indole (a tryptophan precursor) either alone, or after bilharzial infestation, did not show any change in bladder mucosa. Conversely, the insertion of glass beads in the bladder induced carcinomas in 26.6% of mice after 70 weeks. The induction of bladder tumors by glass beads was enhanced by 2-AAF treatment (40%), but not by bilharzia infestation (25%), 2-NA (27%) or indole (27%). The urinary bladders with glass beads were invariably the seat of bacterial infection ( E-coli and gram + ve cocci ) and showed epithelial hyperplasia and metaplasia.

Prognostic value of membrane type 1 and 2 matrix metalloproteinase expression and gelatinase A activity in bladder cancer

PURPOSE To analyze the behavior of matrix metalloproteinases (MMPs) in their active state in patients with bladder cancer. METHOD A retrospective study of 50 patients with localized bladder cancer who underwent tumor resection between June 2006 and June 2007 at the National Cancer Institute in Cairo, Egypt was carried out. Tissue samples were collected and the expression of membrane type 1 (MT1) and type 2 (MT2) MMPs was determined by Western blotting. Gelatinase A (MMP-2) activity was estimated by zymographic analysis in tissue samples of each patient and the values were correlated with clinical tumor stage and lymph node status. RESULT The behavior of MMP-2 showed statistical significance in 90% of tumor tissues compared with 22% of adjacent normal tissues (p<0.001). MT1-MMP was expressed in 88% of tumor tissues compared with 24% of normal tissues (p<0.001); MT2-MMP was expressed in 74% of tumor tissues compared with 12% of normal tissues (p<0.001). While there was a highly significant association between MMP-2 activity and MT1-MMP expression in tumor tissues (p<0.001), there was a moderately significant association between MMP-2 activity and MT2-MMP expression (p=0.018). The results also revealed an association between MT1-MMP and MT2-MMP expression in tumor tissues (p<0.001). MMP-2 activity and MT2-MMP expression in tumor tissues were statistically associated with high tumor stage (p=0.039 and p=0.014, respectively), while the expression of MT1-MMP showed no association with tumor stage (p=0.139). CONCLUSION MMP-2 activity is associated with an increase in MT2-MMP expression and with lymph node metastasis. No association was found between MT1-MMP expression and lymph node metastasis.

Cytotoxic Effects of 2-Methoxyestradiol in the Hepatocellular Carcinoma Cell Line HepG2

Aim: The study was designed to examine the potential cytotoxicity of 2-methoxyestradiol (2ME2), a natural 17β-estradiol metabolite, in hepatocellular carcinoma and the possible underlying mechanisms for this cytotoxicity. Methods: The cell line HepG2 was treated with different concentrations of 2ME2 for 48 and 72 h. Results: Using the sulforhodamine B assay, HepG2 was sensitive to the cytotoxic effect of 2ME2. 2ME2 induced cell arrest at the G2/M phase and a significant high percentage of apoptotic cells compared to the control group. Also, 2ME2 induced a significant increase in caspase 9 enzymatic activity after 48 and 72 h of treatment compared with control values. The DNA laddering was observed only in cells treated for 72 h. Furthermore, 2ME2 induced a significant decrease in the expression levels of vascular endothelial growth factor (VEGF) gene compared to the control values. Conclusion: 2ME2 exerts cytotoxic activity in the HepG2 cell line by preferential cell blocking at the G2/M phase as well as induction of apoptosis as evidenced by increased caspase 9 enzymatic activity and observed DNA laddering in 2ME2-treated HepG2 cells. In addition, a reduction in hypervascularity is an important postulated mechanism as indicated by the significant reduction in the expression of VGEF, one of the most important angiogenic factors.

A study on the etiological factors of bilharzial bladder cancer in Egypt. 6. The possible role of urinary bacteria.

A correlation was obtained between a positive nitrite test in urine and the severity of urinary bacterial infection. Bacteria isolated from the urine of bilharzial or bladder cancer patients were found to be rich in nitrate reductase activity. « Escherichia coli » was the most common microorganism isolated from these specimens. Urine and several urinary constituents activate bacterial nitrate reductase. β-Glucuronidase activity in the urine of patients with chronic « Schistosoma haematobium » infection and bladder cancer was measured and shown to be significantly greater than that of urine of normal control subjects. Urinary bacterial infection was shown to be the source of the increased urinary level of enzyme activity at pH 7.0.

A New Method for Determination of Inorganic Phosphorits in Serum without Deproteinization

A simple method was developed for the determination of inorganic phosphorus in serum without deproteinization. The method is based on the use of formic acid as protein solubilizer and glycerol as stabilizer for the assay system. The optimal conditions for colour development were determined. The results obtained with the new method correlate well with those obtained after deproteinization of serum with trichloroacetic acid. The present method could be fully mechanized, and its application to the determination of serum phosphatases is discussed.

A study on the etiological factors of bilharzial bladder cancer in Egypt: 4. beta-carotene and vitamin A level in serum.

The possible role of vitamin A in the pathogenesis of bilharzial bladder cancer among Egyptians, particularly as it relates to the histopathologic tumor type, was investigated. Bilharzial patients and bladder cancer patients with squamous cell carcinoma, the most prevalent type in Egypt, showed significantly lower levels of vitamin A than normal male subjects. In contrast, bladder cancer patients with transitional cell carcinoma had levels that were not significantly different from normal male subjects. The possible role of vitamin A in the etiology of bilharzial bladder cancer is discussed.