Biomedical subjects

Hak Choy

Publications and source records attributed to Hak Choy.

40 records · Page 3Linked to original sources

PubMed2002

Radiation enhancement by the combined use of topoisomerase I inhibitors, RFS-2000 or CPT-11, and topoisomerase II inhibitor etoposide in human lung cancer cells.

BACKGROUND AND PURPOSE: We have tested the camptothecin analogs, RFS-2000 or CPT-11, in combination with both etoposide and ionizing radiation in vitro to examine the radiation enhancing potential of topoisomerase I plus topoisomerase II (Topo I+Topo II) inhibition in human cancer cells. MATERIALS AND METHODS: H460 human lung carcinoma cells were plated and treated with 10nM RFS-2000 or 4.5microM CPT-11 for 4h. Cells were then irradiated with various doses and treated with 1microM etoposide for 1.5h. Cell survival and sublethal damage recovery (SLDR) were determined by clonogenic assay. 7-aminoactinomycin D (7-AAD) staining and flow cytometry were used to analyze cell viability/apoptosis after combined treatment of drugs with radiation. RESULTS: Survival experiments showed radiation dose enhancement ratios (DER) of 1.26, 1.34, and 1.63 for RFS-2000, etoposide, and RFS-2000 plus etoposide, respectively; the corresponding DER values were 1.30, 1.39, and 1.65 for CPT-11, etoposide, and CPT-11 plus etoposide. The analysis of cell viability/apoptosis using 7-AAD staining and flow cytometry showed an additive effect. Greater inhibition of SLDR was observed with RFS-2000 plus etoposide than with either agent separately, but CPT-11 plus etoposide showed a more modest effect upon SLDR. CONCLUSIONS: These data show that the combination of Topo I inhibitors, RFS-2000 or CPT-11 plus Topo II inhibitor etoposide, is a more effective radiation enhancer than either agent alone in human lung cancer cells. The mechanism of radiation enhancement may involve inhibition of SLDR with RFS-2000 plus etoposide, but other mechanisms may be involved in the combined treatment including CPT-11.

Antineoplastic Agents↗

PubMed2002

Declining hemoglobin during chemoradiotherapy for locally advanced non-small cell lung cancer is significant.

BACKGROUND AND PURPOSE: Tumor hypoxia and anemia have been linked to poor overall survival and local control in carcinomas of both the uterine cervix and the head and neck for patients undergoing radiotherapy. Little is known about the effect of these factors on the outcome of NSCLC patients with locally advanced disease undergoing chemoradiation therapy. MATERIALS AND METHODS: To examine the impact of anemia in stage III NSCLC patients undergoing combined modality therapy, we reviewed our database from three sequential trials of concurrent weekly paclitaxel +/- carboplatin and radiation therapy. 115 pts from 17 institutions were enrolled from 4/94 to 5/97. In this series, hemoglobin values were collected before treatment and weekly during radiotherapy. We correlated baseline Hb and Hb changes during chemoradiation treatment with overall survival. RESULTS: Although pretreatment anemia was common (30% Hb = 110-130 g/l, 16% Hb <110 g/l), log-rank analyses of presenting Hb, average Hb and minimum Hb during treatment were not statistically significantly predictive of survival. However in a Cox model, declining hemoglobin during chemoradiation had a statistically significant impact on survival. CONCLUSIONS: These analyses reveal that a decline in hemoglobin during chemoradiation for stage III NSCLC has a statistically significant correlation with overall survival. Strategies maximizing hemoglobin during combined modality therapy need further exploration in well-planned randomized trials.

Adult↗

PubMed2002

Adjuvant and neoadjuvant treatments for NSCLC.

In stage III non-small cell lung cancer (NSCLC), the use of induction chemotherapy prior to radiotherapy produces a significant increase in median survival of three to four months (from 11 to 14 months), a benefit which appears to be achieved through improved systemic control of the disease. Hyperfractionated radiotherapy, although it enhances local control, seems not to improve survival. Concurrent chemoradiotherapy has emerged as the most successful strategy. It led to increased locoregional control and to a 3-4 month improvement of median survival when compared with induction chemotherapy prior to radiotherapy. Docetaxel is a radiosensitizing agent and has been extensively investigated in phase I/II settings of concurrent chemoradiotherapy. Use of the other cytotoxics such as paclitaxel, or irinotecan in concurrent chemoradiotherapy strategies is also feasible. Of particular interest are the results of SWOG 9504, a phase II study in which cisplatin/etoposide concurrent chemoradiotherapy was followed by three cycles of docetaxel consolidation. Median survival is 26 months, 1-year survival 76% and 3-year survival 40%. These survival data, achieved in pathologically staged IIIB patients, are highly encouraging and support further evaluation of this approach. Among stage III patients eligible for radical treatment with surgery or radiotherapy, the addition of neoadjuvant docetaxel at 100 mg/m(2) for three cycles is tolerable and appears to be associated with a trend towards increased survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Irinotecan in combination with radiation therapy for small-cell and non-small-cell lung cancer.

Lung cancer is the leading cause of cancer-related death in the United States. There was rapidprogress in the treatment of lung cancer duringpast decades, but local control and survival rates are still poor. Radiation therapy has been an indispensable part of the management of lung cancer, and a recent paradigm is concurrent chemoradiation therapy. Many novel chemotherapeutic agents were recently developed to improve both local and systemic control of cancer, including camptothecin derivatives, which are topoisomerase I inhibitors. Irinotecan (CPT-11, Camptosar) is a semisynthetic water-soluble derivative of camptothecin. Irinotecan is active as a single agent against lung cancer, and is also a potent radiosensitizing agent in human lung cancer cell lines and xenografts. There have been many phase I and II clinical trials demonstrating promising results of single-agent irinotecan and combination with concurrent therapy. This article reviews irinotecan's mechanism of action of cytotoxicity and of radiation-sensitizing effects, as well as recent clinical data regarding combining radiation therapy and irinotecan for both non-small-cell and small-cell lung cancer.

Antineoplastic Agents, Phytogenic↗