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Biomedical subjects

S Afzal

Publications and source records attributed to S Afzal.

11 recordsLinked to original sources

[Gallbladder polyps].

Polyps in the gall bladder are detected in 4-5% of the population and most of them are benign. However, they can be premalignant and the prognosis for gall bladder carcinoma is still poor. As with other cancers, treatment at an early stage is therefore, considered essential to improve the prognosis. Because of the very low morbidity after laparoscopic cholecystectomy we recommend laparoscopic cholecystectomy when a polyp in the gall bladder is detected by ultrasonography. A wait and see attitude with repeated ultrasonography twice a year may be chosen, if there are contra-indications to laparoscopic cholecystectomy. If the lesion increases in size, cholecystectomy should be performed.

Gallbladder Neoplasms↗

Study of water quality of Hudiara drain, India-Pakistan.

This paper examines the extent of pollution in Hudiara drain water due to untreated industrial and sewage waste of India and Pakistan. Ninety-nine surface water samples from the Pakistani side of the Hudiara drain were collected during September 1997, and April and June 1998. The analytical results of the Hudiara drain samples point out the industrial and sewage inputs from India and Pakistan. Higher values of biochemical oxygen demand (BOD), chemical oxygen demand(COD), total organic carbon(TOC), and trace metals in drain samples from the Indo-Pak border clearly indicate the Indian industrial and sewage pollution. Large variations in the levels of various measured parameters (COD, BOD, TOC, pH, total soluble substances, and trace metals) were observed along the Hudiara drain in the Pakistani vicinity. These variations were due to different types of industrial effluents and small village drains. The study showed that suspended solids(SS), COD, and fecal coliform (FC) were the major pollutants. Accordingly, the most feasible alternative is to convert the drainage network to a sedimentation and temporary storage reservoir. If disinfected, the runoff water can be used for restricted irrigation. Groundwater samples taken from the drain's surrounding area have also been analyzed. Thirty percent of the samples are not fit for drinking purposes due to NO3-N, Se and FC counts as prescribed by World Health Organization (WHO) guidelines. A trilinear diagram clearly indicates the influence of surface water of the Hudiara drain on ground water; moreover, higher values of nitrate and FC clearly indicate the seepage from the Hudiara drain.

Environmental Monitoring↗

MT1-MMP and MMP-2 mRNA expression in human ovarian tumors: possible implications for the role of desmoplastic fibroblasts.

Expression of activated MMP-2 (72 kDa type IV collagenase) is highly associated with the malignant phenotype in adenocarcinomas, but predominant expression of the mRNA appears to be in stromal cells. MT1-MMP (membrane type 1-matrix metalloproteinase) is implicated in tumor-epithelial cell surface activation of latent pro-MMP-2, indicating a mechanism for tumor-stromal interaction in invasion. We determined the relative mRNA distribution of these MMPs in human ovarian tumors with a view to analyzing potential variations in the epithelial-mesenchymal interactions dictating ovarian tumor cell spread. In situ hybridization using 35S-labeled riboprobes was used to analyze 33 human ovarian tumors and mouse xenografts of human ovarian (DOV 13, SKOV3) and breast (MCF 7) tumor cell lines known to express MT1-MMP and MMP-2. MMP-2 mRNA was expressed in 31 of 33 and MT1-MMP mRNA was expressed in 29 of 33 tumor cases. MMP-2 mRNA was predominantly expressed in desmoplastic fibroblasts and in the subepithelial stroma. MT1-MMP mRNA showed some colocalization with MMP-2 in stromal cells. Neoplastic epithelial cell labeling for MT1-MMP mRNA was present in borderline and malignant tumors but not in benign tumors, and was invariably less than stromal labeling. Xenografts of DOV 13, SKOV 3, and MCF 7 cells showed some stromal localization of MMP-2 mRNA and weak labeling of DOV 13 cells. There was variable labeling for MT1-MMP mRNA in the neoplastic cells only. The colocalization of MT1-MMP and MMP-2 mRNAs in ovarian carcinoma stroma supports the view that MT1-MMP is closely associated with MMP-2 expression and function. It suggests that either additional mechanisms are involved in regulating MMP-2 activation at the tumor cell surface, or more intriguingly, that desmoplastic fibroblasts may be the primary mediators of extracellular matrix remodeling with respect to this system.

Actins↗

Matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression and synthetic matrix metalloproteinase-2 inhibitor binding in ovarian carcinomas and tumor cell lines.

Enhanced matrix metalloproteinase-2 (MMP-2/72-kd type IV collagenase) action correlates with invasion in neoplasia. MMP-2 is inhibited in vivo by tissue inhibitors of metalloproteinases (TIMPs)-TIMP-1 and, especially, TIMP-2. A synthetic, biotinylated inhibitor specific for activated MMP-2 in solution phase, and immunohistochemistry were used to detect MMP-2 and TIMP-2 expression in cell lines and ovarian tumors and to analyze the surface-binding capacity of the inhibitors, which are potential therapeutic agents. Characterization of novel monoclonal antibodies to MMP-2 and TIMP-2 is described together with immunocytochemical staining of 83 paraffin-embedded ovarian tumors (67 malignant, 7 borderline, 9 benign) and 9 cell lines. Synthetic MMP-2 inhibitor binding under controlled conditions was visualized by immunofluorescence and avidin-biotin complex immunoperoxidase methods in cell lines and cryostat sections of ovarian tumors. MMP-2 and TIMP-2 showed heterogenous immunoreactivity, with enhanced staining on high-grade tumors, specifically at the invasive front and in vascular invasion. TIMP-2 immunoreactivity was maximal in malignant cell cytoplasm and less intense in desmoplastic fibroblasts. One monoclonal antibody to MMP-2 showed membrane immunoreactivity, apically polarized in benign and low-grade tumors but depolarized and strong in 37 of 44 cases of high-grade invasive tumors. Eleven of eighteen ovarian carcinomas and six of nine cell lines showed membrane localization of the synthetic inhibitor. Maximal binding occurred in the ovarian cell line OVCA 432 and the breast cell lines MCF 7 and MDA MB 435, all of which were immunoreactive for MMP-2. Cell lines propagated on type I collagen showed no enhancement in inhibitor binding. This study demonstrates cell surface binding of a synthetic MMP-2 inhibitor and provides new evidence of MMP-2 and TIMP-2 immunoreactivity in ovarian carcinomas and cell lines.

Amides↗

MDM2 overexpression is rare in ovarian carcinoma irrespective of TP53 mutation status.

Somatic mutations in TP53 are seen in many human cancers. In addition, the protein product of the wild-type TP53 can be sequestered by the protein MDM2 (murine double minute 2). This protein is commonly overexpressed in human sarcomas and gliomas, usually as a result of gene amplification. In this study, 43 ovarian carcinomas (OCs) were analysed for aberrations in the TP53 gene by immunohistochemistry (IHC), loss of heterozygosity (LOH) or mutation analysis. The MDM2 gene and its product was studied by Southern blotting and IHC. Over 50% of the OCs studied showed mutations in TP53 by either direct sequencing (19/36, 53%), positive IHC (23,43, 53%) or both, whereas 0/32 had amplification of MDM2 and only 1/37 tumours had positive IHC using the anti-MDM2 antibody IF-2. The solitary example of positive IHC in this series was seen in a mixed müllerian tumour with sarcomatous differentiation and was not accompanied by MDM2 DNA amplification. These results support previous data showing that around 50% of OCs have mutations in TP53 and in addition, suggest that MDM2 is not amplified in OC, but the presence of sarcomatous features in mixed müllerian tumours may result in positive immunohistochemistry with IF-2.

Chromosome Deletion↗