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Biomedical subjects

A Lipton

Publications and source records attributed to A Lipton.

At least 127 records · Page 7Linked to original sources

Acute inhibition of rat myometrial responses to oxytocin by tamoxifen stereoisomers and oestradiol.

The non-steroidal antioestrogen tamoxifen (trans-1-(4-beta-dimethylaminoethoxyphenyl)-1,2-diphenylbut- 1-ene), widely used in the treatment of breast cancer, and its oestrogenic cis-isomer rapidly inhibited contractile responses of isolated rat myometrium to supramaximal concentrations of oxytocin (1.28 X 10(-6) mol/l). Both compounds were effective at concentrations comparable with the plasma concentrations of tamoxifen reached in therapy (i.e. 5 X 10(-7) to 5 X 10(-6) mol/l). Inhibition was too rapid in onset (less than 3 min) to involve changes in RNA transcription and protein synthesis, and was not prevented or reversed by the addition of oestradiol to the bath. We conclude that the inhibition did not involve the classical oestrogen receptor pathway. Oestradiol-17 beta at concentrations above 10(-6) mol/l also inhibited the myometrium and potentiated the effects of the anti-oestrogens. Our experiments suggest that the anti-oestrogens and oestradiol act via a similar route with tamoxifen having an equilibrium affinity approximately tenfold greater than that of oestradiol.

Animals↗

The in vitro interaction of RA-233 and several interferons on human cell lines.

The antiproliferative effects of six different human interferons were examined in two human cell lines: HM7 (human melanoma cell line) and MDA-MB-231 (human breast carcinoma cell line). A dose-response curve was developed for each interferon in which the maximum dose applied gave at least 30% growth inhibition of control values after 96-128 hours of continuous exposure. An amount of RA-233 which caused 25% growth inhibition (0.05 mg for both HM7 and MDA-MB-231 cell lines) was added to the cultures with various doses of each interferon. The inhibitory effects of RA-233 and each interferon were additive at low concentrations. In no case was a synergistic effect observed. Unlike with human fibroblast interferon, we could not show a synergistic inhibitory effect between RA 233 and any of the six different interferons on these two human epithelial tumor cell lines.

Breast Neoplasms↗

Venous thrombosis as a side effect of tamoxifen treatment.

We report what we believe to be an infrequent but noteworthy complication of antiestrogen therapy with tamoxifen. Seven patients developed venous thrombosis or pulmonary embolism within 6 months of starting treatment. Guidelines similar to those employed in younger women treated with anovulatory drugs would appear indicated.

Antineoplastic Combined Chemotherapy Protocols↗

Radioimmunoassay of a cancer-related glycoprotein. Circulating levels.

Circulating levels of (a) tumor-related glycoprotein(s) were determined by radioimmunoassay for a variety of patients and controls, and correlated with sialic acid concentration. Levels were highest in patients with metastatic disease and progressively declined to those with localized disease receiving therapy. Values for normal, adjuvant, and cured patients were significantly lower. Sialic acid concentrations correlated best for the metastatic group but not for the normals.

Female↗

Corynebacterium parvum versus BCG adjuvant immunotherapy in human malignant melanoma.

One-hundred and sixteen patients with Stage I and Stage II malignant melanoma were randomized to treatment with either Bacillus Calmette-Guerin (BCG) (Tice) or subcutaneous Corynebacterium parvum (Burroughs-Wellcome). Life table analysis failed to reveal a difference between these two forms of treatment in 68 Stage I patients. The relapse rate was significantly reduced in Stage II patients treated with C. parvum.

BCG Vaccine↗

Clinical and biochemical effect of aminoglutethimide in the treatment of advanced prostatic carcinoma.

Treatment of male patients with advanced prostatic carcinoma and disease progression after initial endocrine therapy frequently is unsatisfactory. However, approximately 20 per cent of these patients respond to surgical adrenalectomy or hypophysectomy, indicating continued hormonal responsiveness. A total of 25 previously castrated men with stage D carcinoma received 1,000 mg. aminoglutethimide and 40 mg. hydrocortisone daily. The patients were evaluated using the criteria of the National Prostatic Cancer Project. One patient has had a complete response and is in remission after 275 weeks of therapy. A partial response was noted in 4 patients, while the disease was objectively stable in 6. Pre-treatment testosterone and dihydrotestosterone levels were measured in 9 of 25 patients and were significantly reduced statistically during aminoglutethimide therapy (p less than 0.01). Response and drug toxicity are discussed.

Adenocarcinoma↗

Inhibition of wound healing by topical steroids.

A new animal model was used to study the effect of topical agents on wound healing. A weak- (hydrocortisone cream 1%) and medium-strength (fluocinolone acetonide ointment 0.025%) steroid and their vehicles were applied to full-thickness skin wounds placed on the backs of female Syrian hamsters. Wound healing was significantly retarded by both steroids when compared to their vehicles. Fluocinolone had a greater inhibitory effect than hydrocortisone.

Administration, Topical↗

Cis-platinum ototoxicity: clinical experience and temporal bone histopathology.

A clinical and pathologic study of cis-platinum ototoxicity was performed. Twenty-four patients treated with cis-platinum for head and neck cancer were studied prospectively. Post cis-platinum hearing losses were subclinical, detected in 25% of patients, isolated to 4 and 8 kHz, and did not exceed 25 dB at any frequency. Temporal bones from a 9-year-old with frontal lobe astrocytoma and with cis-platinum ototoxicity were studied with routine and special techniques to elucidate oto and neurotoxicity. Degenerative changes in the outer hair cells in the lower turns of the cochlea, in the spiral ganglion, and cochlear nerve were the most striking findings.

Adult↗

A method for collecting detailed data on direct and indirect medical expenses of cancer patients.

A complex data collection system involving seven community based practices and a university affiliated hospital has been developed. Four types of data are being collected: 1) medical status, 2) billings for a six month period, 3) patient reports of direct and indirect costs for a six month period and how they affected family finances and 4) diaries of direct and indirect costs for a week in which treatment was received and a week in which treatment was not received. Three groups are involved in collecting these data: physicians, their office staff and a central project telephone interviewer. Office staff are paid overtime rates for their work which is in addition to their regular responsibilities. Telephone follow-up interviews have contributed to compliance and have helped insure consistency in the data. Two hundred and fifteen patients have provided complete information to date. Refusal rate has been approximately 26% and drop out rate among persons enrolled in the study has been 21%. Patients most difficult to recruit and hold in the study have been very sick, elderly or on welfare. Total direct costs of data collection are estimated to be $48.00 per patient.

Data Collection↗

A study of prostaglandin E2, parathormone, and response to indomethacin in patients with hypercalcemia of malignancy.

In order to evaluate the relationship of PGE2 to hypercalcemia in cancer patients, 101 patients were screened with a radioimmunoassay for plasma prostaglandin E2 (PGE2) (NL less than 100 pg/ml). Of the 101 patients, 31 were hypercalcemia. Mean PGE2 (+/- SEM) of the 31 patients was 199 +/- 36 pg/ml. Among the 70 normocalcemic patients, mean +/- SEM PGE2 was 85 +/- 12 pg/ml (range = less than 25--225 pg/ml) (P less than 0.001). Seventeen hypercalcemic patients were initially treated with saline and furosemide, then were prospectively screened for serum parathormone (iPTH) and PGE2. Fourteen of 17 patients were then treated empirically with indomethacin (25 mg b.i.d.) for 72 hours and the PGE2 assay was repeated. Prior to therapy with indomethacin (mean +/- SEM), Ca++ = 12.2 +/- 1.5 mg/dl (NL 8.4--10.6 mg/dl), PGE2 = 87.1 +/- 36.8 pg/ml, (range = less than 25--209 pg/ml), and iPTH = 406 +/- 266 pg/ml (NL less than 400 pg/ml) (range = less than 100--825 pg/ml). PGE2 was elevated before treatment in 6/14 patients (breast, colon, renal, lung, neck tumors, and myeloma). Following treatment with indomethacin, PGE2 and calcium fell to normal levels in three patients (breast, colon, renal carcinomas). These results suggest: (1) A bimodal distribution of PGEs exists in hypercalcemic cancer patients. (2). There was some evidence of lack of whole molecule iPTH suppression in these patients. (3) Multiple stimuli of calcium mobilization may play an important etiologic role in a few hyercalcemic cancer patients and may explain the failure of indomethacin to control serum Ca++ in some patients with elevated PGE2.

Humans↗

Estrogen receptor status in inflammatory breast carcinoma.

Sixteen women with a clinical diagnosis of inflammatory breast carcinoma had estrogen receptor analysis performed. Eleven of 16 were premenopausal. Median age of all patients was 46 years. All patients had estrogen receptor (ER) assay by either dextran charcoal method or by sucrose gradient method. Five patients were ER + ( greater than or equal to 10 fmol/mg cytosol protein) and 11 were ER -, with almost no binding at all. Response to therapy for metastatic disease using either hormones or chemotherapy was disappointing.

Antineoplastic Agents↗

Aminoglutethimide as treatment of postmenopausal women with advanced breast carcinoma.

Hormone-dependent breast carcinomas respond to deprivation of biologically active estrogens with objectively quantifiable tumor regression. Aminoglutethimide, a known inhibitor of steroid synthesis, is also a potent blocker of the aromatase enzyme and, thus, of estrogen production. We developed an effective regimen to inhibit estrogen production in postmenopausal women using aminoglutethimide and replacement glucocorticoid. One hundred forty-seven women initially received aminoglutethimide and replacement glucocorticoid as treatment of metastatic breast carcinoma. One hundred twenty-nine women are currently evaluable for assessment of clinical and hormonal responses. Thirty-seven percent of unselected women and 49% of estrogen receptor-positive patients experienced objective tumor regression. Responses occurred predominantly in soft tissue (47%) and bone (35%) and lasted 30 +/- 9.1 months for complete and 14 +/- 1.5 months for partial regressions. Plasma and urinary estrogen levels fell equally in responder versus nonresponder groups whereas androgen levels declined less in patients with progressive disease.

Aminoglutethimide↗

Cross-over comparison of tamoxifen and aminoglutethimide in advanced breast cancer.

Thirty-four postmenopausal patients with advanced breast cancer had an overall objective response rate of 47% when treated with aminoglutethimide and hydrocortisone initially and a response rate of 24% when crossed over to therapy with tamoxifen after progression on aminoglutethimide. A similar group of 32 patients experienced a response rate of 28% when treated with tamoxifen first and a 19% objective response rate on subsequent therapy with aminoglutethimide. Patients who failed to respond to the first therapy seldom responded on cross-over to the alternate therapy. Toxicities were acceptable with both forms of therapy. Tamoxifen and aminoglutethimide used sequentially are effective forms of palliative hormonal therapy in metastatic breast cancer.

Aminoglutethimide↗