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Biomedical subjects

V Liengswangwong

Publications and source records attributed to V Liengswangwong.

8 recordsLinked to original sources

Point: the potential importance of elective nodal irradiation in the treatment of non-small cell lung cancer.

Patients who receive radiation therapy for non-small cell lung cancer (NSCLC) will require accurate targeting of the grossly involved primary and nodal disease. However, the treatment of grossly uninvolved elective nodal sites that may harbor microscopic occult disease is controversial. In simple terms, physicians are guided by 1 of 2 paradigms when they decide about the use of elective nodal irradiation in NSCLC. First, one may consider that high doses of radiation therapy for the primary and grossly involved lymph nodes represents the most important aspect of treatment and that elective irradiation of potential occult micrometastasis is not necessary because it may limit the doses that can be given to the gross disease. Additionally, this line of thought often includes the belief that most or all patients with occult micrometastasis are not curable. Alternatively, one may consider that the evidence for a dose response, for grossly involved NSCLC, beyond 60 Gy is very limited and that the omission of elective nodal irradiation obviates the chance for cure in many patients. These small deposits of tumor in regional nodes are common, are amenable to low doses of radiation (50 Gy), and treatment of these lesions does result in cures. This review focuses on this latter paradigm and the available evidence to support it.

Carcinoma, Non-Small-Cell Lung↗

Long term results of a phase I/II study of aggressive chemotherapy and sequential upper and lower hemibody radiation for patients with extensive stage small cell lung cancer.

BACKGROUND: A Phase I/II study of an aggressive six-drug chemotherapy regimen followed by the use of sequential hemibody radiation therapy as a possible non-cross-resistant systemic treatment was undertaken for patients with extensive stage small cell lung cancer. METHODS: The 20 enrolled patients received 7 cycles of cyclophosphamide-based chemotherapy. The first cycle consisted of cyclophosphamide, doxorubicin, etoposide, vincristine, and lomustine. Subsequent cycles used a regimen of doxorubicin alternating with cisplatin. Thoracic radiation was delivered in a split-course fashion during the first week of chemotherapy cycles 5 and 6 (2000 cGy in five fractions during each week). Prophylactic cranial radiation was delivered in a split-course fashion during the first week of chemotherapy cycles 2 and 3 (1700 cGy in 5 fractions during each week). After the 7 cycles, patients received 600 cGy upper hemibody radiation followed by 800 cGy lower hemibody radiation. RESULTS: Nineteen of 20 patients were evaluable for toxicity and response to treatment. Hematologic toxicity accounted for treatment delays or decreased doses in 16 of 19 patients. Thirteen patients completed the initial 7 cycles; progressive disease was the only reason for discontinuing treatment. Two patients had fatal hematologic complications after lower hemibody radiation. Three patients had severe or greater peripheral neurologic toxicity, two had severe central neurologic toxicity, and one had severe cardiac toxicity. Of 19 patients, 9 achieved a complete response; median survival was 11.5 months. Five-year progression free survival and 5-year overall survival were 27% and 16%, respectively. CONCLUSIONS: This aggressive regimen is feasible for patients with extensive stage small cell lung cancer; however, hematologic-related mortality after lower hemibody radiation suggests that future investigations should be initiated at lower initial doses of lower hemibody radiation. Long term survival of the patients suggests that sequential hemibody radiation treatment warrants further investigation.

Adult↗

Prophylactic cranial irradiation in limited-stage small cell lung cancer.

BACKGROUND: The role of prophylactic cranial irradiation (PCI) for patients with limited-stage small cell lung cancer (LSSCLC) remains a controversial issue. This study evaluated PCI in patients with LSSCLC who achieved a complete response to initial chemotherapy. METHODS: A retrospective case study of all nonprotocol patients with LSSCLC examined at our institution from 1982 to 1990 was performed. Of the 67 nonprotocol patients who were treated with combination chemotherapy (cyclophosphamide-based) and thoracic radiotherapy during those years, 43 achieved a complete response. Twenty-four patients received prophylactic cranial irradiation (PCI+) (25-36 Gy in 10-16 fractions), and 19 did not (PCI-) at the physician's or patient's discretion. RESULTS: The distribution of prognostic factors between the PCI+ and PCI- groups was well balanced. Of the PCI+ patients, the 2-year actuarial freedom from relapse in the central nervous system was 93% versus 47% for the PCI- patients (log rank analysis, P = 0.001). An initial central nervous system relapse developed in 2 of the 24 PCI+ patients as the only site of failure versus 7 of 19 PCI- patients (P = 0.003). The 2-year actuarial overall survival was 50% for the PCI+ patients versus 21% for the PCI- patients (P = 0.01). The addition of prophylactic cranial irradiation was the only significant factor contributing to an improvement in time to central nervous system relapse and survival for the PCI+ patients. There were five patients alive at the time of this report, and all received prophylactic cranial irradiation. None had cognitive or neurologic impairment. CONCLUSIONS: Prophylactic cranial irradiation may contribute to improved survival in patients with LSSCLC who achieve a complete response after chemotherapy and thoracic radiation therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Topoisomerase II-independent doxorubicin-induced cytotoxicity in an extremely doxorubicin-resistant cell line.

Lepidopteran insect cells (TN-368) were found to be extremely resistant to the anthracycline, doxorubicin. They were approximately 400 fold more resistant to the cytotoxic effects of doxorubicin compared to a mammalian counterpart; V79 hamster lung fibroblast cells. Doxorubicin accumulated into TN-368 cells and bound to DNA in a similar fashion as the interaction of doxorubicin in V79 cells. However, no doxorubicin-induced stabilized DNA-topoisomerase II complexes could be demonstrated in TN-368 cells (even at the high concentrations of doxorubicin that resulted in cytotoxicity). Therefore, the lack of formation of this critical lesion may be the cause of the marked doxorubicin resistance noted in the TN-368 cells.

Animals↗

Limited-stage small-cell lung cancer: patterns of intrathoracic recurrence and the implications for thoracic radiotherapy.

PURPOSE: This analysis was performed to determine the most appropriate volume that should be encompassed by thoracic radiation treatments (TRTs) for patients with limited-stage small-cell lung cancer (LSSCLC) who have responded to initial chemotherapy. PATIENTS AND METHODS: A retrospective review of all patients (N = 67) with LSSCLC who were not entered onto a research protocol and were treated at our institution between the years of 1982 and 1990 was performed. Fifty-nine of 67 patients had adequate information regarding the size of the tumor before the start of chemotherapy (computed tomographic [CT] scan of chest or chest x-ray), the size of the tumor before TRT, and the TRT field size based on a simulation radiography. All 59 patients were treated with cyclophosphamide-based chemotherapy, and TRT was generally delivered concomitantly with chemotherapy following two to three cycles of chemotherapy alone. RESULTS: Of 59 patients, 28 were treated with TRT field sizes that encompassed postchemotherapy tumor volumes, and 31 patients were treated with TRT field sizes that encompassed prechemotherapy tumor volumes (defined as a volume that included at least a 1.5-cm margin on the prechemotherapy tumor volume). Nineteen patients had an intrathoracic recurrence of disease as the first site of recurrent small-cell carcinoma: 10 of 31 patients treated with TRT fields that encompassed prechemotherapy tumor volumes and nine of 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes. For the 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes, the greatest distance that the prechemotherapy tumor volume (without margins) extended beyond the edge of the TRT field was 0.5 to 5.0 cm, with a median of 2.5 cm. All 19 of the intrathoracic recurrences were in-field failures, although two patients (one prechemotherapy volume and one postchemotherapy volume) did have concurrent pleural effusions. CONCLUSION: These results indicate that the use of TRT fields that encompass postchemotherapy tumor volumes does not increase the risk of marginal failures or intrathoracic failures outside the TRT field.

Actuarial Analysis↗

Etoposide-resistance in the multidrug-resistant LZ-8 cells.

The multidrug-resistant LZ-8 cells were found to exhibit marked resistance to etoposide compared to wild-type, parental V79 cells. The multidrug resistant phenotype did not significantly contribute to this etoposide-resistance. Following exposure of LZ-8 cells and V79 cells to equivalent concentrations of etoposide, there was a dramatic reduction in the number of etoposide-induced stabilized DNA-topoisomerase II complexes in the LZ-8 cells compared to V79 cells, however, this reduction was not found when nuclei isolated from LZ-8 and V79 cells were exposed to equivalent concentrations of etoposide. These results suggest that cytoplasmic factors are involved in the etoposide-resistance of LZ-8 cells.

Animals↗

Characterization of allergens from spores of the oyster mushroom, Pleurotus ostreatus.

Crude extracts of Pleurotus ostreatus spores obtained from a single local source were fractionated by gel filtration to resolve the allergenic components. The fraction pool corresponding to 10.5 to 25 kd molecular weight contained allergenic activity as demonstrated by both RAST and skin testing. Similar results were obtained with extracts from spores that originated in four other areas and with extracts prepared from P. sajor-caju spores obtained from commercially produced caps. The RAST-active fraction was further separated by hydrophobic interaction chromatography (HIC). HIC fraction pools were assayed for allergen(s) by RAST inhibition and immunoblotting of isoelectric focused polyacrylamide gels. RAST-inhibition data indicated that the allergen(s) was reversibly bound to the HIC column, eluting with 2, 1, and 0.15 mol/L of buffered salt solutions. After electrofocusing, these fractions yielded 15, 12, and 11 Coomassie brilliant blue-staining bands, respectively. IgE binding occurred with 7, 8, and 6 of these bands, as revealed by radiostaining of the immunoblots. These procedures help identify P. ostreatus spore allergens and allow a greater degree of standardization in the preparation of allergen extracts from basidiospores for use in diagnosis and therapy of fungal allergy.

Allergens↗

Basidiospore allergens: determination of optimal extraction methods.

Five methods were tested by RAST for allergen extraction from seven basidiospore species Armillaria tabescens, Chlorophyllum molybdites, Coprinus quadrifidus, Pleurotus ostreatus, Calvatia cyathiformis, Pisolithus tinctorius, and Scleroderma sp. With each basidiospore type, extracted allergen activity varied according to the method employed. In general, defatting of spores with ethyl ether, followed by homogenization in 0.125 M NH4HCO3 buffer, resulted in greatest allergen yield. In order to compare extracts from different isolates, batches of Pleurotus ostreatus spores obtained from different locations and over different time periods were analysed. Spores harvested from the same basidiomycete species in different areas varied in allergen (RAST) and protein (HPLC profile) content. The spores obtained from the same location over a 1-2 year period did not differ significantly. These results indicate that basidiospores can be stored for several years and that spore extracts from different locations can vary. These studies will help in the future to provide better characterized extracts for clinical studies.

Allergens↗