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Biomedical subjects

V K Sangar

Publications and source records attributed to V K Sangar.

9 recordsLinked to original sources

Differential radiosensitisation by ZD1839 (Iressa), a highly selective epidermal growth factor receptor tyrosine kinase inhibitor in two related bladder cancer cell lines.

The epidermal growth factor receptor (EGFR) is expressed in a wide variety of epithelial tumours including carcinoma of the bladder. Stimulation of the EGFR pathway is blocked by ZD1839 (Iressa), a highly selective EGFR tyrosine kinase inhibitor. Radical radiotherapy is an established organ sparing treatment option for muscle invasive bladder cancer and this study has explored the possibility for the use of ZD1839 as a radiosensitiser in this scenario. The effect of combination treatment with ZD1839 (0.01 microM) and ionising radiation in the established bladder cancer cell lines MGH-U1 and its radiosensitive mutant clone S40b was measured by clonogenic assays. A highly significant radiosensitising effect was seen in both cell lines (P < 0.001 for MGH-U1 and S40b cell lines). This effect was independent of the concentration of the drug and the duration of exposure prior to treatment with ionising radiation. Cell cycle kinetics of both cell lines was not significantly altered with ZD1839 (0.01 microM) as a single agent. A modest induction of apoptosis was observed with ZD1839 (0.01 microM) as a single agent, but a marked induction was observed with the combination treatment of ZD1839 and ionising radiation. These results suggest a potentially important role for ZD1839 in combination with radiotherapy in the treatment of muscle invasive bladder cancer.

Antineoplastic Agents↗

An evaluation of gemcitabines differential radiosensitising effect in related bladder cancer cell lines.

The aim of this study was to establish the radiosensitising properties of gemcitabine in a pair of related bladder tumour cell lines with differential radiosensitivity. The radioresistant bladder tumour cell line MGH-U1 and its radiosensitive mutant clone, S40b (both p53 mutant), had SF(2) values (surviving fraction at 2 Gy) of 0.98 and 0.64, respectively (P<0.001). Colony-forming assays showed that at 0.01 microM gemcitabine radiosensitisation occurred only in the S40b cell line (dose-modifying factor (DMF)=1.4). At 0.3 microM (killing 50% of cells), both cell lines were radiosensitised; DMF=2.25 and 1.2 for MGH-U1 and S40b, respectively. These data suggest that gemcitabine is an effective radiosensitiser in bladder cancer cell lines, with greater sensitisation in the radioresistant parental line-a feature that should be useful in a clinical setting.

Antimetabolites, Antineoplastic↗

Development of a novel rapid assay to assess the fidelity of DNA double-strand-break repair in human tumour cells.

Cellular survival following ionising radiation-mediated damage is primarily a function of the ability to successfully detect and repair DNA double-strand breaks (DSBs). Previous studies have demonstrated that radiosensitivity, determined as a reduction in colony forming ability in vitro, may be related to the incorrect repair (misrepair) of DSBs. The novel rapid dual fluorescence (RDF) assay is a plasmid-based reporter system that rapidly assesses the correct rejoining of a restriction-enzyme produced DSBs within transfected cells. We have utilised this novel assay to determine the fidelity of DSB repair in the prostate tumour cell line LNCaP, the bladder tumour cell line MGH-U1 and a radiosensitive subclone S40b. The two bladder cell lines have been shown in previous studies to differ in their ability to correctly repair plasmids containing a single DSB. Using the RDF assay we found that a substantial portion of LNCaP cells [80.4 +/- 5.3(standard error)%] failed to reconstitute reporter gene expression; however, there was little difference in this measure of DSB repair fidelity between the two bladder cell lines (48.3 +/- 3.5% for MGH-U1; 39.9 +/- 8.2% for S40b). The RDF assay has potential to be developed to study the relationship between DSB repair fidelity and radiosensitivity as well as the mechanisms associated with this type of repair defect.

Cell Survival↗

Diagnosis of a liver abscess with Ga-67 and radiocolloid tomography.

A 46 year-old white male with fever of unknown origin demonstrated a multiloculated hepatic cyst on abdominal CT. Persistent fever and leukocytosis prompted Tc-99m Sulfur colloid liver-spleen and gallium-67 citrate imaging to identify a possible liver abscess. SPECT imaging provided pertinent clinical information that allowed the diagnosis of abscess to be made.

Citrates↗

Acid phosphatase production as an aid in rapid characterization of Candida species.

Yeast isolates were tested for phosphatase activity, using p-nitrophenyl phosphate substrate. Several Candida species displayed characteristic patterns. The enzyme activity was absent in all except one of the 78 isolates of Candida albicans tested. C. tropicalis, C. pseudotropicalis, and C. krusei were the most consistent and active enzyme producers. Enzyme production by these yeasts was not influenced by the amount of growth or a decrease in the pH of the culture media. The characteristic enzyme activity of these three yeasts was demonstrated in the presence of concentrations of inorganic phosphate which inhibited the enzyme activity of other Candida species. The activity of isolates of C. gullermondii, C. parapsilosis, and C. stellatoidea was variable, although none of these were strong enzyme producers. It seems feasible to use phosphatase activity as a simple and rapid additional method for the separation of C. albicans from closely related species of the genus.

Acid Phosphatase↗

Polysaccharide produced by Anacystis nidulans: its ecological implication.

An extracellular polysaccharide from Anacystis nidulans was extracted from cell-free medium. Analysis showed that the polysaccharide consisted of glucose, galactose, and mannose in the ratio of 60:14:20. The production of polysaccharide depends on the age of culture, the growth temperature, and the form of nitrogen available.

Cell-Free System↗