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Biomedical subjects

G Fisher

Publications and source records attributed to G Fisher.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas.

Only 10% to 20% of patients with pancreatic cancer are considered candidates for curative resection at the time of diagnosis. We postulated that preoperative chemoradiation therapy might promote tumor regression, eradicate nodal metastases, and allow for definitive surgical resection in marginally resectable patients. The objective of this study was to evaluate the effect of a preoperative chemoradiation therapy regimen on tumor response, resectability, and local control among patients with marginally resectable adenocarcinoma of the pancreas and to report potential treatment-related toxicity. Patients with marginally resectable adenocarcinoma of the pancreas (defined as portal vein, superior mesenteric vein, or artery involvement) were eligible for this protocol. Patients received 50.4 to 56 Gy in 1.8 to 2.0 Gy/day fractions with concurrent protracted venous infusion of 5-fluorouracil (250 mg/m2/day). Reevaluation for surgical resection occurred 4 to 6 weeks after therapy. Fifteen patients (9 men and 6 women) completed preoperative chemoradiation without interruption. One patient required a reduction in the dosage of 5-fluorouracil because of stomatitis. Acute toxicity from chemoradiation consisted of grade 1 or 2 nausea, vomiting, diarrhea, stomatitis, palmar and plantar erythrodysesthesia, and hematologic suppression. CA 19-9 levels declined in all nine of the patients with elevated pretreatment levels. Nine of the 15 patients underwent a pancreaticoduodenectomy, and all had uninvolved surgical margins. Two of these patients had a complete pathologic response, and two had microscopic involvement of a single lymph node. With a median follow-up of 30 months, the median survival for resected patients was 30 months, whereas in the unresected group median survival was 8 months. Six of the nine patients who underwent resection remain alive and disease free with follow-up of 12, 30, 30, 34, 39, and 72 months, respectively. Preoperative chemoradiation therapy is well tolerated. It may downstage tumors, sterilize regional lymph nodes, and improve resectability in patients with marginally resectable pancreatic cancer. Greater patient accrual and longer follow-up are needed to more accurately assess its future role in therapy.

Adenocarcinoma↗
PubMedDate not supplied

Use of N-sigma-dansyl-L-lysine and flow cytometry to identify heat-killed mammalian cells.

We have employed the nontoxic fluorescent membrane probe, N-sigma-dansyl-L-lysine (DL) to study the effect of mild (45.5 degrees C) heat shock on a variety of mammalian cell lines. It has been previously proposed by Humphries and Lovejoy (1983) that DL selectively partitions into (and diffuses through) membranes whose component molecules have undergone lateral phase separation resulting in the formation of phospholipid domains. Excellent flow cytometric resolution of the DL staining cells from several cell lines was obtained by using bivariate (forward angle light scatter versus DL-fluorescence) analysis. Dye uptake and release data as well as measurement of the octanol: water partition coefficient (7.2) all indicated that the stain was likely associated with the plasma membrane. After heating, all cell lines exhibited a time-dependent increase in the fraction of cells stained by DL. Nearly all of the DL-staining cells were propidium iodide and trypan blue excluding. Exclusion of erythrosin B or inclusion of fluorescein showed a better correlation with colony formation, although neither was found to be as effective as DL in estimating cell killing. A comparison of cell survival curves as measured either by colony formation or by the fraction of cells not stained by DL 24 h after heating indicated a good, though not absolute correlation. These results indicate first that DL may have general usefulness as a stain indicating cell death following heat shock, and second, that DL may have utility as a probe of specific membrane damage induced by heat. Our results are consistent with the hypothesis that membrane lateral phospholipid domain partitioning is associated with hyperthermia-induced cell death in mammalian cells.

Animals↗
PubMedDate not supplied

Mammalian cell survival studies characterizing multiport negative pi-meson irradiation with the Stanford Medical Pion Generator (SMPG).

Radiobiological measurements have been made under various conditions of muliport pion irradiation using the Stanford Medical Pion Generator (SMPG). Chinese hamster cells (HA-1) were suspended in a tissue-equivalent 25% gelatin/medium solution. Hypoxic and aerobic HA-1 cells were irradiated simultaneously in a cylindrical water tank at either 4 or 16 degrees C. Irradiation at the focus of 60 converging pion beams, at a peak dose rate of 6 rads/min, gave relative biological effectiveness (RBEs) of 2.8, 1.8 and 1.4 at 50, 20 and 5% survival, respectively, and an oxygen enhancement ratio (OER) of 1.7. Plateau irradiation with crossing pion beams, at a peak dose-rate of 3 rads/min, resulted in survival values very close to those obtained with similar doses of 85 kV X-rays. Preliminary studies with large irradiation volumes in broadened pion stopping regions indicate RBEs significantly > 1 for survival > 50%. Supporting microdosimetric data with the SMPG are consistent with the radiobiological results.

Animals↗