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Biomedical subjects

T C Hamilton

Publications and source records attributed to T C Hamilton.

184 records · Page 11Linked to original sources
PubMedDate not supplied

Genome scanning detects amplification of the cathepsin B gene (CtsB) in transformed rat ovarian surface epithelial cells.

OBJECTIVE: To isolate a portion of the amplicon inferred to be present in a malignant rat tumor cell line, NuTu 26, by the presence of a homogeneously staining chromosomal region (hsr) and identify genes embedded within it. METHODS: Genome scanning was used to identify an EcoRI fragment (8.6 kbp) within the amplified region of the NuTu 26 genome using a recently identified rat repetitive sequence, OST17 as a probe. The 8.6 kbp amplified fragment was sequenced and used as starting material to obtain additional sequence information by screening a P1 clone-derived DNA library to identify any genes likely embedded in the amplicon. Use of the microdissected hsr as a probe for fluorescence in situ hybridization (FISH) and application of Southern, Northern, and Western blot analysis confirmed the amplification of this region in the NuTu 26 genome. RESULTS: The cathepsin B gene was within the amplicon of the hsr-containing marker chromosome of NuTu 26. FISH analysis and chromosomal banding further revealed that the marker chromosome was a derivative of chromosomes 4 and 15, i.e., der(15)t(4;15). CONCLUSION: Cathepsin B gene amplification may contribute to some aspect of the biology of ovarian cancer. This concept is strengthened by the finding that the gene is overexpressed frequently in independently transformed rat ovarian surface epithelial cells.

Animals↗
PubMedDate not supplied

Stereoselective pharmacokinetics of L-buthionine SR-sulfoximine in patients with cancer.

Buthionine sulfoximine (BSO) is an inhibitor of glutathione synthesis that can deplete intracellular glutathione and reverse resistance to platinating and alkylating agents in vitro and in vivo. We are performing a phase I study of BSO in combination with melphalan. The BSO used in this study was provided by the National Cancer Institute and is a mixture of the R- and S-diastereomers of L-BSO. We developed a reversed-phase HPLC assay to quantitate levels of the R- and S-BSO isomers in plasma and urine. The pharmacokinetics of BSO was determined in 11 patients: 3 patients at 5 g/m2, 4 patients at 7.5 g/m2, and 4 patients at 10.5 g/m2. Plots of plasma area under the concentration-time curve vs. dose for both R-BSO (r2 = 0.798) and S-BSO (r2 = 0.752) are linear, indicating linear pharmacokinetics in this dose range. However, the individual BSO isomers exhibit stereoselective disposition and elimination. Values for steady-state volume of distribution and renal clearance were similar for both isomers, but total clearance, nonrenal clearance, and half-life were approximately 25% different, with the R-(inactive) isomer being eliminated faster (higher clearance and shorter half-life) than the S- (active) isomer. Using a paired t test, we found that the pharmacokinetic parameters, total clearance, nonrenal clearance, and half-life for R-BSO were significantly different (p < 0.05) from those for S-BSO. Renal clearance of both S- and R-isomers approximated glomerular filtration rate and accounted for 64% of S-BSO total clearance and 56% of R-BSO total clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMedDate not supplied

Early ovarian cancer: a review of its genetic and biologic factors, detection, and treatment.

Early-stage ovarian carcinoma requires comprehensive surgical staging; reexploration for patients who had suboptimal initial surgery would indicate an apparent early ovarian carcinoma. After proper surgery, patients can be subdivided into a high- or low-risk group, and treatment options then can be discussed with the patient. Patients in the low-risk category can be followed up expectantly without any form of adjuvant therapy. Patients in the high-risk category, however, should be encouraged to participate in randomized clinical trials, because it is unclear at the current time which combination of chemotherapy and how many treatments should be used. A platinum-based paclitaxel regimen probably should be used, although the relative merits of carboplatin and cisplatin and the appropriate schedule for taxol (1 hour vs. 3 hours vs. 24 hours vs. 96 hours) are yet unknown. It is hoped that clinicians will continue to encourage patients to participate in randomized clinical trials so that optimal therapy for early ovarian cancer can be established.

Biomarkers, Tumor↗