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Biomedical subjects

S Phuphanich

Publications and source records attributed to S Phuphanich.

28 records · Page 2Linked to original sources

Response of recurrent brain metastases in malignant melanoma to 5-fluorouracil and interferon-alpha therapy.

A 36-year-old woman underwent removal of a stage II malignant melanoma from the left ankle in 1985. A single brain metastasis to the right frontal lobe was removed in July 1986. Postoperatively, she received 5-fluorouracil, cisplatin, and etoposide (VP-16) in conjunction with radiation therapy. She achieved remission until March 1988, when left hemiparesis occurred suddenly. Computed tomography and magnetic resonance scans revealed multiple brain metastases. She was treated with a combination of 5-fluorouracil, 1,000 mg/m2 in a 24-hour continuous IV infusion for 5 days; interferon-alpha, 10 million units in subcutaneous injection daily for 10 days; and oral cimetidine, 1,200 mg daily for 7 days. This regimen, repeated every 4 to 6 weeks for four cycles, was well tolerated, with complete remission of neurological deficits and resolution of the lesions seen on the brain scans until she died 11 months later of intracranial hemorrhage secondary to severe thrombocytopenia.

Adult↗

MRI: stability of three supervised segmentation techniques.

Supervised segmentation methods from three families of pattern recognition techniques were used to segment multispectral MRI data. Studied were the maximum likelihood method (MLM), k-nearest neighbors (k-NN), and a back-propagation artificial neural net (ANN). Performance was measured in terms of execution speed, and stability for the selection of training data, namely, region of interest (ROI) selection, and interslice and interpatient classifications. MLM proved to have the smallest execution times, but demonstrated the least stability. k-NN showed the best stability for training data selection. To evaluate the segmentation techniques, multispectral images were used of normal volunteers and patients with gliomas, the latter with and without MR contrast material. All measures applied indicated that k-NN provides the best results.

Adult↗

Long-term survival in malignant glioma. Prognostic factors.

Mean survival of patients with malignant glioma is six months. Only 7.5% of these patients survive two years. We identified 14 patients, nine with glioblastoma multiforme and five with anaplastic astrocytoma, who survived more than two years. All were treated initially with surgery, radiation and adjuvant chemotherapy. One patient who received three years of nitrosourea has lived longer than 7.3 years. Seven of the 14 patients have no sign of tumor recurrence four years after diagnosis. Nine surviving patients were younger than 45 years of age at the time of diagnosis. Five died of tumor recurrence with the median survival time of 3.5 years. This data suggests that onset at a younger age (< 45 years), multimodality therapy, high Karnofsky Performance Scale and frontal lobe tumors were the major prognostic factors that contributed to long-term survival.

Adolescent↗

Phase II study of combined carmustine, 5-fluorouracil, hydroxyurea, and 6-mercaptopurine (BFHM) for the treatment of malignant gliomas.

The Neuro-oncology Service of the University of California Brain Tumor Research Center conducted a nonrandomized phase II study to evaluate, in patients with recurrent malignant glioma, the benefit of a four-drug combination (BFHM) consisting of carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea), 5-fluorouracil, hydroxyurea, and 6-mercaptopurine. There were 29 evaluable glioblastoma multiforme patients and 45 nonglioblastoma anaplastic glioma patients available for analysis. Tumor progression was analyzed as the primary study endpoint. Of the glioblastoma patients, 16 of 29 (55%) responded or stabilized on therapy; of the other anaplastic gliomas, 32 of 45 (71%) responded or stabilized. For patients who stabilized or responded to treatment, BFHM achieved a median time to tumor progression of 46 weeks with a 25th percentile time to tumor progression of 68 weeks for anaplastic gliomas and a median time to tumor progression of 23 weeks with a 25th percentile time to tumor progression of 36 weeks for glioblastoma multiforme patients. A Cox multivariate analysis demonstrated that age and Karnofsky score were important prognostic variables for these patients.

Adolescent↗

Phase I study of intravenous bromodeoxyuridine used concomitantly with radiation therapy in patients with primary malignant brain tumors.

We report here the results of a Phase I study conducted to determine the toxicity and serum levels that could be tolerated by patients receiving i.v. bromodeoxyuridine (BUdR) concomitantly with radiation therapy. Because of severe thrombocytopenia and leukopenia that was produced in three patients treated by a 96 hour infusion of BUdR at a dose of 1.5 g/m2/24 hours, the dose was reduced to 0.8 g/m2/24 hours in these patients and the remaining 9 patients in the study group. Even at this dosage, myelotoxicity was observed. BUdR levels were measured by an isocratic high performance liquid chromatographic (HPLC) method developed for this study. Results of in vitro studies conducted by others suggest that serum levels produced in our patients by administration of doses of 0.6 to 0.8 g/m2/24 hours should be adequate to achieve a therapeutic effect.

Adult↗

Supratentorial malignant gliomas of childhood. Results of treatment with radiation therapy and chemotherapy.

Twenty-seven patients aged 1 to 18 years harboring supratentorial (20 in the cerebrum and seven in the thalamus) malignant gliomas were treated between 1975 and 1982. There were four glioblastomas multiforme, 14 anaplastic astrocytomas, and nine malignant gliomas. All patients had a subtotal resection or biopsy as the initial procedure and received postoperative radiation therapy (RT). Fifteen of 27 patients were treated by RT alone; 14 had tumor progression with a median time to tumor progression (MTP) of 65 weeks. Twelve patients were treated with chemotherapy as an adjuvant to RT; only seven had tumor recurrence, with an MTP of 130 weeks. Of the 21 patients with recurrent tumors in both groups, 18 were treated with chemotherapy alone, or chemotherapy with a second surgical procedure or second course of RT. For all histological grades of tumor, the MTP for first recurrence was 75 weeks and the median survival time was 180 weeks. Age at initial diagnosis was found to be a statistically significant prognostic factor, with patients younger than 10 years of age surviving longer than patients aged over 10 years (p = 0.02).

Adolescent↗

Unsupervised measurement of brain tumor volume on MR images.

We examined unsupervised methods of segmentation of MR images of the brain for measuring tumor volume in response to treatment. Two clustering methods were used: fuzzy c-means and a nonfuzzy clustering algorithm. Results were compared with volume segmentations by two supervised methods, k-nearest neighbors and region growing, and all results were compared with manual labelings. Results of individual segmentations are presented as well as comparisons on the application of the different methods with 10 data sets of patients with brain tumors. Unsupervised segmentation is preferred for measuring tumor volumes in response to treatment, as it eliminates operator dependency and may be adequate for delineation of the target volume in radiation therapy. Some obstacles need to be overcome, in particular regarding the detection of anatomically relevant tissue classes. This study shows that these improvements are possible.

Adult↗

Neurotransmitter control of growth hormone secretion in children after cranial radiation therapy.

Cranial radiation for childhood cancer can cause growth hormone deficiency (GHD), usually due to hypothalamic rather than pituitary dysfunction. To investigate whether this hypothalamic dysfunction is secondary to altered neurotransmitter input from other brain centers, we used neurotransmitter-excitatory substances to study the GH secretory response in 17 children who had received 12 to 60 Grey (Gy) to the cranium and 40 short children with normal endocrine function. As expected, the irradiated children had decreased mean GH secretion in response to insulin-induced hypoglycemia and arginine infusion, and decreased mean 24 hour GH concentrations, compared to the control group. In contrast, the two groups had similar GH secretory responses to GHRH stimulation and somatostatin suppression. Assessment of neurotransmitter pathways in the irradiated children revealed significantly lower mean peak GH concentrations in response to 5 of the 6 substances tested compared to control children: alpha-adrenergic stimulation (clonidine), beta-adrenergic blockade (propranolol), cholinergic stimulation, dopaminergic stimulation (L-dopa), and GABA-ergic stimulation (valproic acid). Results of serotonergic stimulation (L-tryptophan) were not statistically significant. Eleven patients who had abnormal GH secretion underwent 4 or more tests with neurotransmitter-stimulatory agents; 3 patients had peak GH concentrations of < 2.5 micrograms/l to all tests, whereas 4 patients had a peak GH concentration of > or = 7 micrograms/l to one or more tests but < 5 micrograms/l to one or more other tests. These observations suggest that radiation damage may sometimes spare growth hormone-releasing hormone (GHRH) and somatostatin secretion while affecting neurotransmitter pathways. We postulate that the hierarchy of sensitivity to radiation damage may be hypothalamic and extra-hypothalamic neurotransmitters > hypothalamic GHRH and/or somatostatin secretion > pituitary GH secretion.

Adolescent↗

Modulation of glioma cell growth and 5-lipoxygenase expression by interferon.

The effect of mouse interferon-alpha/beta (MuIFN-alpha/beta on growth/viability, cell cycle regulation, 5-lipoxygenase (5-LO) protein expression, leukotriene B4 (LTB4) biosynthesis and glial fibrillary acidic protein (GFAP) expression of mouse glioma (G-26) cells in vitro was studied. The G-26 cells were treated with 800 IU/ml of MuIFN-alpha/beta for 1, 2, 3 and 4 days. The growth and viability of glioma cells was evaluated by [3H]-thymidine incorporation and MTT (3(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazoliumbromi de) assay, resulted in a time dependent decrease in [3H]-thymidine incorporation into DNA and MTT formazan formation, respectively. The cell cycle regulation measured by flow cytometry with propidium iodide staining revealed that the cell multiplication cycle was slowed down due to accumulation of cell in S-phase of the cell cycle, leading to inhibition in G0/G1 phase of the cell cycle. The 5-LO protein expression (measured by Western immunoblot analysis) and LTB4 biosynthesis (measured by enzyme immunoassay) were found to be increased by 2 to 2.4 fold and several fold respectively on days 3 and 4 of MuIFN-alpha/beta treatment. The GFAP protein expression was also found to be increased at least by 3 fold on day 4 of the MuIFN-alpha/beta treatment. These results suggest that inhibition in growth and thereby slowing of the cell multiplication cycle of glioma cells has resulted in upregulation of GFAP expression and 5-LO pathway.

Animals↗