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Biomedical subjects

S L Gibson

Publications and source records attributed to S L Gibson.

At least 73 records · Page 4Linked to original sources
PubMed1984

Hematoporphyrin derivative-induced photosensitivity of mitochondrial succinate dehydrogenase and selected cytosolic enzymes of R3230AC mammary adenocarcinomas of rats.

The photosensitizing activity of hematoporphyrin derivative (HPD) was investigated by studying selected enzymes localized to mitochondria and cytosol of R3230AC mammary adenocarcinomas. Experiments in vitro demonstrated that mitochondrial succinate dehydrogenase was inhibited in a drug dose- and light exposure time-related manner; at 7.0 micrograms of HPD per ml or higher, enzyme activity was inhibited greater than 50% after 15 min of photoradiation. The three cytosol enzymes studied under the same conditions in vitro demonstrated different photosensitivities. Pyruvate kinase activity was significantly inhibited in a dose- and time-related fashion, whereas lactate dehydrogenase was inhibited to a lesser extent, and glucose phosphate isomerase activity was inhibited only at the highest dose (70 micrograms of HPD per ml) used. The time-course of these responses was examined with an in vivo-in vitro protocol, consisting of photoradiation of mitochondria and cytosol prepared from tumors obtained at various times (up to 1 week) after a single injection of HPD (80 mg/kg). Pyruvate kinase activity was markedly inhibited at early times returning to initial levels by 48 hr; neither lactate dehydrogenase nor glucose phosphate isomerase was inhibited by this treatment. Mitochondrial succinate dehydrogenase and cytochrome c oxidase activities displayed significant photoradiation-induced inhibitions, with greatest inhibition occurring between 24 and 96 hr after injection of HPD; at 1 week, succinate dehydrogenase activity had returned to its initial level, but cytochrome c oxidase activity remained significantly inhibited. These data suggest that HPD-induced photosensitization of mitochondria may be an important site of action contributing to tumor cell cytotoxicity and regression as a result of photoradiation therapy.

Adenocarcinoma↗
PubMed1983

Photosensitization of mitochondrial cytochrome c oxidase by hematoporphyrin derivative and related porphyrins in vitro and in vivo.

Mitochondrial cytochrome c oxidase activity was inhibited by exposure to hematoporphyrin derivative followed by photoirradiation. Inhibition of enzyme activity in vitro was a dose- and time-related event, the log of percentage inhibition being linear with time. Exposure of mitochondria to hematoporphyrin or hydroxyethylvinyldeuteroporphyrin sensitized mitochondria to photoirradiation, whereas protoporphyrin IX was only weakly active as a photosensitizer for inhibition of cytochrome c oxidase. Mitochondria from mammary glands of pregnant rats showed hematoporphyrin-induced photosensitivity similar to those from R3230AC mammary adenocarcinomas. Mitochondria prepared from tumors of animals given injections of hematoporphyrin derivative in vivo and then photoirradiated in vitro demonstrated considerable sensitivity to light as reflected by significant inhibition of cytochrome c oxidase activity. A side by side comparison of hematoporphyrin derivative with hematoporphyrin, using this in vivo-in vitro experimental protocol, indicated that photosensitivity was retained for a longer time after treatment with hematoporphyrin derivative. Taken together, these data provide a potential mechanism of action, i.e., inhibition of respiration, for porphyrin-induced photosensitivity, and they offer a useful assay to investigate this family of therapeutic agents.

Animals↗
PubMed1982

A logistic model based on enzyme activities for the prediction of response of breast cancer patients to chemotherapy.

A logistic regression model, utilizing the activities of certain selected glycolytic enzymes and ER status measured on primary or recurrent lesions, has been applied to predict for response to combination chemotherapy regimens administered to women with advanced breast cancer. The clinical outcome of response or no response was evaluated retrospectively using criteria employed by cooperative group protocols. In 93 cases, 58/61 patients classified as nonresponders and 22/32 patients demonstrating objective responses would have been correctly designated, based on the 50% estimated probability as the level for separation of responders from nonresponders. The overall predictive accuracy of this model was 86%, with apparently greater accuracy for prediction of lack of response. Addition of estrogen receptor status to the model imparted no gain in accuracy of prediction. Application of this model to a prospective study is warranted.

Adult↗
PubMed1981

Seatone in arthritis.

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Anti-Inflammatory Agents↗
PubMed1981

Seatone in arthritis.

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Anti-Inflammatory Agents↗
PubMed1981

Low tissue enzyme activity seen in breast cancers of patients who fail adjuvant chemotherapy.

Primary breast cancers from 54 patients undergoing postsurgical adjuvant chemotherapy were analyzed for several enzymes and estrogen receptors to determine if biochemical parameters might offer a prognostic index for determining outcome of therapy. Recurrence of disease during therapy or within 12 months after cessation of therapy was the criterion for classifying the patient as a treatment failure. Recurrence rates were similar in ER-positive vs. ER-negative patients, indicating that estrogen receptor status offered no predictive value in this series. However, patients who failed therapy had tumors that displayed significantly lower activities of lactate dehydrogenase, glucosephosphate isomerase, and glucose 6-phosphate dehydrogenase vs. patients who showed no evidence of recurrence for this observation period. When either premenopausal or ER-negative patients were compared, a similar observation was made; low enzyme activities occurred in patients failing to benefit from adjuvant chemotherapy. Based on this series of patients, it is suggested that a selected enzyme activity profile may offer a predictive index for recurrence in the adjuvant chemotherapy setting.

Breast Neoplasms↗
PubMed1980

The lack of relationship between estrogen receptor status and response to chemotherapy.

The possible relationship between estrogen receptors and response of breast cancer patients to chemotherapy was examined in two situations: patients with advanced disease and patients receiving post-surgical adjuvant treatment. In 73 patients with disseminated disease, no relationship between ER status and response to cytotoxic chemotherapy was observed. At this time, 44 of these cases have undergone extramural review; in these 44 cases, we observed no significant relationship between ER status and response to chemotherapy. In a series of 52 patients receiving adjuvant therapy, 27 patients were classified as failures due to recurrence. ER status did not offer prognostic value for failure of patients treated with postsurgical adjuvant therapy. We conclude that the prognostic value of ER data in nonhormonal therapy settings remains to be proven

Antineoplastic Agents↗
PubMed1980

The relative importance of estrogen receptor analysis as a prognostic factor for recurrence or response to chemotherapy in women with breast cancer.

The value of estrogen receptor (ER) analysis in primary breast cancer samples as a potential prognostic factor was examined in three clinical situations: time to recurrence in patients with no therapy after mastectomy, failure of patients receiving adjuvant therapy, and response of advanced disease patients to cytotoxic chemotherapy. Other prognostic factors analyzed were menopausal and nodal status. In none of these clinical settings were we able to demonstrate the usefulness of ER status as a prognosticator of the disease course or its response to therapy.

Antineoplastic Agents↗
PubMed1980

Homoeopathic therapy in rheumatoid arthritis: evaluation by double-blind clinical therapeutic trial.

Twenty-three patients with rheumatoid arthritis on orthodox first-line anti-inflammatory treatment plus homeopathy were compared wtih a similar group of twenty-three patients on orthodox first-line treatment plus an inert preparation. There was a significant improvement in subjective pain, articular index, stiffness and grip strength in those patients receiving homoeopathic remedies whereas there was no significant change in the patients who received placebo. Two physicians were involved in prescribing for the patients and there were no significant differences in the results which they obtained. No side effects were observed with the homoeopathic remedies.

Adult↗
PubMed1980

The use of genetic linkage in counselling families with dystrophia myotonica.

The linkage between the secretor locus (Se) and the locus for the dystrophia myotonica gene (Dm) has been studied in eight families. It was hoped that this linkage would be of use for detecting carriers of the Dm gene prior to the onset of clinical signs. It proved to be of help in four out of the eight families, though for only a proportion of the individuals at risk. In one family prenatal diagnosis would have been possible for the mother of the proband, but she elected to be sterilised. In a ninth family in which the diagnosis is not yet established, prenatal diagnosis would be feasible should the proband prove to have myotonic dystrophy. Cases of infantile DM occurred in four of the eight families. In all instances, the gene was inherited from the mother. The incidence of miscarriage and neonatal death was six times as high in the families of DM sufferers as in the families of their normal siblings.

Adolescent↗
PubMed1980

The secretor status of the foetus.

One hundred amniotic fluids were tested for the presence of ABH blood group substances. Gestation at amniocentesis ranged from 12 to 28 weeks, with a mean of 16.6 weeks. The secretor status of the fluid was correlated with the secretor status of the baby after birth as determined from a sample of saliva. Fluid and saliva correlated in 98% of cases. It is felt that contamination with blood is likely to be the main source of error in typing amniotic fluids. However, because of the weaker activity of the anti-H serum, the detection of the presence or absence of H-substance can be doubtful if duplicate tests are not carried out. It is recommended that all fluids be checked for contamination with blood and that duplicate assays be done on two successive occasions. If these precautions are taken, the secretor typing of the amniotic fluid accurately reflects the secretor status of the individual foetus. Though probably not of wide application, the test could be of value in prenatal detection of dystrophia myotonica in individual cases.

ABO Blood-Group System↗
PubMed1980

Regulation of estrogen-binding capacity by insulin in 7,12-dimethylbenz(a)anthracene-induced mammary tumors in rats.

The role of insulin as a regulator of estrogen receptors (ER's) was investigated in 7,12-dimethylbenz(a)anthracene-induced mammary tumors in diabetic and insulin-treated rats. Induction of diabetes with streptozotocin produced regression of lesions classified as insulin dependent; lesions that continued to grow in diabetic rats were classified as insulin independent. Compared to tumors in intact hosts [ER, 39 +/- 4 (S.E.) fmol/mg cytosol protein], regressing insulin-dependent lesions had ER levels of 8.5 +/- 0.7 fmol, and insulin-independent tumors had ER levels of 24 +/- 3 fmol. Treatment of diabetic rats with insulin 8 IU/day, caused insulin-dependent regressing tumors to resume growth; these lesions had ER levels of 53 +/- 10 fmol. Insulin-independent lesions in diabetic rats demonstrated two patterns after treatment with insulin; continued growth resulted in tumors having ER levels of 28 +/- 11 fmol, whereas insulin-induced tumor regression resulted in tumors that demonstrated ER levels of 40 +/- 6 fmol/mg cytosol protein, a value equal to the level of ER in tumors growing in intact rats. Scatchard analysis of the saturation-binding data gave linear representations, and the estimated Kd for the ER was comparable for all groups, ranging from 0.44 to 1.90 x 10(-9) M. Several additional tumors were classified as demonstrating static growth. When this behavior represented a response due to insulin treatment, ER levels were elevated. Static tumors remaining static after insulin treatment demonstrated low ER levels. We conclude that (a) cessation of tumor growth after induction of diabetes resulted in reduction of ER levels, (b) treatment with insulin that resulted in an altered tumor growth was accompanied by elevated ER levels, and (c) insulin may play a role in regulation of ER independent of tumor growth.

9,10-Dimethyl-1,2-benzanthracene↗