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Side effects of chemotherapy are a major impediment in the treatment of cancer. Cyclotherapy is an emerging therapeutic strategy for protecting normal cells from the side effects of chemotherapy. Low, non-genotoxic doses of known p53 activators can be used to induce p53-dependent cell cycle arrest in normal cells bearing wild-type p53. This cytostatic(More)
Samples of gall bladder bile from patients with and without carcinoma of the gallbladder were examined for lipid peroxidation (free radical oxidation) products. 4-hydroxynonenal (HNE) was found in higher concentration in the bile of patients with carcinoma of the gall bladder. There was also a highly significant difference in the concentration of HNE among(More)
Gallbladder cancer is a common malignancy among women in India. The aetiology of gallbladder carcinoma is still obscure and although numerous factors have been implicated, none has stood the test of time. This study was carried out to evaluate the role of lipid peroxidation product 4-hydroxynonenal (HNE) in gallbladder carcinogenesis. High-performance(More)
Although the influence of thyroid dysfunction on the effectiveness and disposition of drugs has been extensively studied, the pharmacokinetic/pharmacodynamic interactions between cardiac glycosides and antithyroid drugs have not been investigated. This possibility arose following the clinical observation of relatively lower digoxin plasma levels in 1(More)
Pharmacological activation of wild-type p53 has been found to protect normal cells in culture from cytotoxicity and nuclear aberrations caused by conventional cancer therapeutics. Hence, small-molecule p53 activators could have clinical benefits as chemoprotectants for cancer patients bearing p53-mutant tumors. We have evaluated 16 p53-based cyclotherapy(More)
Detection in blood of the genetic and epigenetic changes present in metastatic cancers is opening up new possibilities in molecular diagnostics. A number of methodological and clinical issues await resolution before serum epigenetic biomarkers can be considered a routine part of the management of melanoma patients following primary excision. However, there(More)
p53-Based cyclotherapy is proving to be a promising approach to palliate undesired effects of chemotherapy in patients with tumours carrying p53 mutations. For example, pre-treatment of cell cultures with Nutlin-3, a highly-selective inhibitor of the p53-mdm2 interaction, has been successfully used as a cytostatic agent to protect normal cells, but not(More)
The enzyme N-myristoyltransferase (NMT) from Trypanosoma brucei has been validated both chemically and biologically as a potential drug target for human African trypanosomiasis. We previously reported the development of some very potent compounds based around a pyrazole sulfonamide series, derived from a high-throughput screen. Herein we describe work(More)
her illness. Case 2.?P., aged 32 years, a Hindu female, illness of five days; she was taken ill on 17th February, 1932, and I saw the patient on the 22nd February. Temperature? 102.5?F., pulse 130, and soft, semi-comatose, breathing laboured, lying in her bed with the right thigh semiflexed. The eyes were much congested; she could be raised only after much(More)
A screen of a focused kinase inhibitor library against Trypanosoma brucei rhodesiense led to the identification of seven series, totaling 121 compounds, which showed >50 % inhibition at 5 μm. Screening of these hits in a T. b. brucei proliferation assay highlighted three compounds with a 1H-imidazo[4,5-b]pyrazin-2(3H)-one scaffold that showed sub-micromolar(More)