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Biomedical subjects

G T Chen

Publications and source records attributed to G T Chen.

At least 109 records · Page 6Linked to original sources
PubMed1984

Postmortem examination of 22 pancreatic carcinoma patients treated with helium ion irradiation.

Postmortem findings are available in this report in 22 patients with pancreatic carcinoma treated with helium ions at Lawrence Berkeley Laboratory; California. This represents the largest group evaluated histologically in the literature and is the first report evaluating effects of particle radiation in pancreatic tissue. Patient survival after therapy averaged 9 months. Most died of infection and/or pulmonary emboli. Local control was achieved in 27%. The pancreatic tumors had histologically more severe radiation changes than nontumor bearing pancreas. Irradiated bone marrow was severely hypocellular, and irradiated skin was atrophic. Five patients had radiation injury in the gastrointestinal tract. The spinal cord, liver, and kidneys showed no damage. This study demonstrates the safety of helium particle irradiation with present therapeutic planning. Injury to tumor was seen without excessive damage to adjacent tissues.

Adult↗
PubMed1983

Helium charged-particle radiotherapy of locally advanced carcinoma of the esophagus, stomach, and biliary tract.

Sixty-five patients with squamous carcinoma of the esophagus (32 patients), carcinoma of the stomach (18 patients) and carcinoma of the biliary tract (15 patients) received from 6000 to 7000 equivalent rad (60-70 Gray-equivalents) of helium radiotherapy at 2.0 GyE per fraction, four fractions per day, using multiportal, spread-out Bragg peak therapy. All patients had locally advanced disease without evidence of distant metastases. Partial compensation for tissue inhomogeneities was accomplished. Although palliation of symptoms and regression of tumor was commonly seen, local failure occurred in most patients (77%). The median survival was 8 months. It does not appear that an increase in tumor dose relative to normal tissues can be achieved that would be high enough to increase locoregional control rates over historical control rates with low-LET irradiation. Further studies will be carried out with heavier particles such as neon or silicon in hopes of achieving greater biological effect on these difficult-to-control tumors.

Adenocarcinoma↗
PubMed1982

Hepatitis B vaccine in medical staff of hemodialysis units: efficacy and subtype cross-protection.

We evaluated the efficacy of hepatitis B vaccine (Heptavax-B) containing only the ad subtype in a randomized, placebo-controlled, double-blind trial among 865 staff members of 43 hemodialysis units in the United States. Surface antibody developed in 92.6 per cent of the subjects after two doses of vaccine and in 96 per cent after the six-month booster. The incidence of infections with hepatitis B virus (with or without hepatitis) was 9.9 per cent in placebo recipients and 2.2 per cent in vaccine recipients (P less than 0.01). The two cases of hepatitis B among vaccine recipients did not occur in subjects in whom antibody had developed. In 81 per cent of the hepatitis events, the virus was of the ay subtype. The indicence of ay virus was 8.2 per cent among placebo recipients and 1.2 per cent among vaccine recipients (P less than 0.005). We conclude that these data confirm the efficacy of the vaccine and demonstrate subtype cross-protection.

Adult↗
PubMed1982

Metabolism of androstenedione by guinea-pig peritoneal macrophages: synthesis of testosterone and 5 alpha-reduced metabolites.

Androstenedione metabolizing enzymes present in guinea-pig peritoneal macrophages were investigated using tritium-labeled androstenedione as the substrate. We found that the metabolites of [3H]-androstenedione produced by these macrophages were testosterone, 5 alpha-androstane-3,17-dione, isoandrosterone, androsterone, 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol. The rates of metabolite formation remained linear as a function of time of incubation for approximately 30 min and with macrophage number up to 2 x 10(7) cells per ml. The formation of these metabolites in indicative that the following androstenedione metabolizing enzymes are present in guinea-pig peritoneal macrophages: 5 alpha-reductase, 3 alpha-hydroxysteroid oxidoreductase, 3 beta-hydroxysteroid oxidoreductase and 17 beta-hydroxysteroid oxidoreductase. It is possible, therefore, that the macrophage, in vivo, may play a role in the metabolism of blood-borne androstenedione to potent androgens. These hormones are important in the regulation of many biological processes, possibly including the activity of the macrophage itself.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1982

Treatment of cancer with heavy charged particles.

A clinical radiotherapeutic trial using heavy charged particles in the treatment of human cancers has accrued over 400 patients since 1975, 378 of whom were treated with particles and 28 with low LET photons as control patients. Heavy charged particle radiotherapy offers the potential advantages of improved dose localization and/or enhanced biologic effect, depending on particle selected for treatment. Target sites have included selected head and neck tumors, ocular melanomata, malignant gliomata of the brain, carcinoma of the esophagus, carcinoma of the stomach, carcinoma of the pancreas, selected juxtaspinal tumors and other locally advanced, unresectable tumors. A Phase III prospective clinical trial has been started in carcinoma of the pancreas using helium ions. Phase I-II studies are underway with heavier particles such as carbon, neon and argon ions in order to prepare for prospective Phase III trials. Silicon ions are also under consideration for clinical trial. These studies are supported by the United States Department of Energy and National Institutes of Health.

Adult↗
PubMed1982

Syntheses and adrenergic agonist properties of ring-fluorinated isoproterenols.

2-Fluoro-, 5-fluoro-, and 6-fluoroisoproterenol were synthesized by reduction of the Schiff base formed between the corresponding ring-fluorinated 3,4-bis(benzyloxy)phenethanolamine and acetone, followed by reductive debenzylation in the presence of oxalic acid to yield crystalline neutral oxalates. The apparent beta-adrenergic potencies were determined in the isolated guinea pig atria. 2-Fluoro- and 5-fluoroisoproterenol were equipotent with (+/-)-isoproterenol, while 6-fluoroisoprotenol was virtually inactive. No alpha-adrenergic agonist activity (guinea pig aorta) was shown by any of the fluoroisoproterenols. Displacement of alpha- and beta-specific radioligands from isolated membrane preparations from rat brain by the fluoroisoproterenols were in agreement with the responses of the organ preparations. Thus, the apparent fluorine-induced specificity is due to specificity at the receptor binding site. The effects of fluorine substitution are discussed with regard to the apparent negative influence of the 6-fluoro substituent on the beta-agonist properties of isoproterenol, the lack of any increase in potency due to the 2-fluoro substituent, and the possibility of fluorine-induced changes in the electron density of the aromatic ring as a possible rational for the fluorine-induced specificity of both the fluoroisoproterenols and the fluoronoirepinephrines.

Adrenergic alpha-Agonists↗
PubMed1982

Clinical problems in radiotherapy of carcinoma of the pancreas.

Since 1975, 94 patients with localized unresectable carcinoma of the pancreas have been irradiated using helium and heavier particles at the University of California Lawrence Berkeley Laboratory. Despite surgical exploration and an extensive diagnostic workup including radiological, nuclear medicine, and computer-assisted tomographic studies, many patients proved to have occult liver metastases manifested within 9 months post treatment. In addition, local and regional control of the primary neoplasm (approximately 20%) has been difficult to obtain even with doses of 6000 equivalent rad in 7 1/2 weeks. Gastric and biliary obstruction have required surgical bypass procedures since irradiation has not been successful in relieving obstructive symptoms. Evidence of gastrointestinal injury has been present in postradiation therapy in approximately 10% of patients, a figure which might be higher if more patients had a longer survival (average 10 months). Some patients require pancreatic enzyme supplementation because of pancreatic deficiency either secondary to tumor or treatment. Further improvement in local control and survival requires better diagnostic methods for evaluation of local and metastatic spread, improved therapy for local and regional disease, as well as therapy directed at occult liver metastases that are frequently present.

Adenocarcinoma↗
PubMed1980

Current status of clinical particle radiotherapy at Lawrence Berkeley Laboratory.

Clinical experience with charged particle irradiation of human cancers has been underway at the University of California Lawrence Berkeley Laboratory. Over 150 patients have been irradiated with heavy charged particle beams including helium, carbon, neon, and argon ions. Pilot studies have included such tumor sites as glioma of the brain, carcinoma of the esophagus, carcinoma of the pancreas, carcinoma of the stomach, ocular melanoma, and carcinoma of the uterine cervix. Prospective studies are planned to investigate the improved dose localization potential (helium) and the enhanced biologic and physical dose potential (carbon, neon) in a controlled trial against the best available megavoltage irradiation techniques.

Argon↗
PubMed1980

Helium ion charged particle therapy for choroidal melanoma.

Nine patients with choroidal melanomas were treated with helium ion charged particle irradiation. No patient demonstrated tumor enlargement, and most lesions followed for more than five months have demonstrated tumor shrinkage. The most effective method of choroidal melanoma management is unclear. Heavy charged particle irradiation may be more applicable and have less ocular morbidity associated with it in either radioactive plaques or photocoagulation.

Adult↗
PubMed1980

Radiotherapy with heavy charged particles at Lawrence Berkeley Laboratory.

Since July 1975, 157 patients have been irradiated with heavy charged particles at the Lawrence Berkeley Laboratory in a Phase I-II clinical trial to study the usefulness of these particles in the irradiation of human cancers. The particles utilized have included helium, primarily of interest because of improved dose distributions with reduction of dose to adjacent normal tissues, and heavier particles such as carbon, neon and argon ions which have the additional potential of increased biologic effectiveness against the tumor, especially hypoxic tumor cells. Initial results with helium particles have been sufficiently good to warrant a Phase III randomized trial in carcinoma of the pancreas; in other tumor sites, and with other particles, Phase I -- Phase II studies are in progress. Although follow-up is short, control within the irradiated area in this heterogeneous group of patients appears at least as good as with current megavoltage irradiation and complications to date are acceptably low, warranting further studies with heavy charged particles.

Argon↗
PubMed1980

Computerized tomography in the quantitative assessment of tumour response.

While Computerized Tomographic (CT) scans have been a valuable asset to radiotherapy treatment planning, their role in the critical assessment of tumour response has been less well defined. Recent refinements in radiotherapy treatment techniques have intensified the need for non-invasive methods to evaluate the local control of inaccessible neoplasms. In this study, 20 cases in which both pre- and post-treatment CT scans were available up to 27 months post-therapy were reviewed. The majority of the patients had pancreatic carcinoma. In both pre- and post-therapy scans, the tumour volume was calculated from contours outlined on sequential CT slices. These interpretations were compared with surgical findings, clinical course and patient survival. The rate of the primary tumour regression had little bearing on the clinical outcome. However, there was CT scan evidence of initial local tumour stabilization or regression in > 80% of the cases. In addition, CT scan evidence of tumour progression was correlated with clinical progression in > 90% of the patients. This suggests that a growth delay analysis might be possible with the use of CT scans, at least for the evaluation of pancreatic carcinoma.

Humans↗
PubMed1979

5 alpha-Reductase activity in human placenta.

The concentration of 5 alpha-pregnane-3,20-dione in peripheral blood of pregnant women is higher than that found in blood obtained from nonpregnant women throughout the luteal phase of the ovulatory cycle. The in vitro synthesis of 5 alpha-reduced pregnanes from [3H]progesterone by placental tissue was investigated using tissue minces and homogenates in the presence of added nicotinamide-adenine dinucleotide phosphate. The metabolites, [3H]5 alpha-pregnane-3,20-dione and [3H]3 beta-hydroxy-5 alpha-pregnan-20-one, were isolated and characterized employing a combination of chromatographic techniques, derivative formation, and crystallization with authentic [14C]5 alpha-pregnane-3,20-dione and [14C]3 beta-hydroxy-5 alpha-pregnan-20-one to constant 3H:14C ratios. In short-term incubations with placenta homogenates, the apparent pH optimum for the synthesis of 5 alpha-pregnane-3,20-dione was 8.8. There was no evidence for the formation of 5 beta-reduced pregnanes from [3H]progesterone by placental tissue. The in vitro metabolism of [3H]progesterone by minces of five term placentas, during 1 hour incubations at pH 7.4, was studied. The rate of formation of 5 alpha-pregnane-3,20-dione varied from 109 to 197 pmoles/gm placental tissue/hr.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗