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Biomedical subjects

A Lipton

Publications and source records attributed to A Lipton.

At least 145 records · Page 8Linked to original sources
PubMed1982

Adjuvant antiplatelet therapy with aspirin in colo-rectal cancer.

Sixty-six patients with Duke's B2 or C colon or rectal cancer were randomized for treatment with aspirin (ASA), 600 mg, p.o., twice daily x 2 years or placebo (P). Compliance was checked in both groups by random measurement of blood salicylate levels. Fifty-seven patients are currently evaluable. No difference in disease-free (p = .66) or overall survival (p = .90) is present between ASA and P groups. The time at which ASA therapy is started (within 2 or within 4 weeks) following surgery does not affect these results. Aspirin at conventional dosage is ineffective in preventing the appearance of metastases in patients with colo-rectal cancer.

Actuarial Analysis↗
PubMed1982

Randomized trial of aminoglutethimide versus tamoxifen in metastatic breast cancer.

We compared antiestrogen therapy (tamoxifen) with an estrogen suppression regimen (aminoglutethimide-hydrocortisone) in postmenopausal women with metastatic breast carcinoma. Fifteen of 39 patients (38%) who received tamoxifen experienced an objective tumor regression (3 complete, 12 partial remissions), whereas 13 of 36 women (36%) receiving aminoglutethimide responded (one complete remission, 12 partial remissions). The median duration of response was similar. The site of tumor involvement appears to be important in choosing between these hormonal treatments. Aminoglutethimide appears to offer a greater chance of response in patients with bone involvement.

Aminoglutethimide↗
PubMed1982

Adequacy of estrogen suppression with aminoglutethimide and hydrocortisone as treatment of human breast cancer: correlation of hormonal data with clinical responses.

Human breast neoplasms can be divided into hormone-dependent and hormone-independent subtypes. Estrogen is the major hormonal stimulus for growth of the dependent tumors. Failure to respond to estrogen suppression therapy could reflect either an incomplete lowering of estrogens or the hormonal independence of the tumor. To address this issue, we compared the levels of several estrogens and other hormones in women experiencing objective responses (the responders) and disease progression (the progression group) during therapy with the aromatase-steroidogenesis inhibitor, aminoglutethimide, and replacement hydrocortisone. Pretreatment hormonal profiles of the estrogens, and androgens, ketosteroids, thyroxine, polypeptide hormones, and carcinoembryonic antigen did not differ significantly among response groups. During treatment, the levels of all estrogens were suppressed to a similar degree in the progression group and in the responders. Urinary estrone, for example, fell to 16.7 +/- 3.2% of basal in the responders versus 16.3 +/- 3.8% of basal in the progression group. These data suggested that lack of estrogen suppression did not explain the response to treatment in the patients receiving aminoglutethimide-hydrocortisone. This finding differs from our results in a similarly analyzed control group of patients treated with surgical adrenalectomy. Levels of the weak androgens, dehydroepiandrosterone sulfate and androstenedione, were found to be higher in the progression group compared to the responders. This observation could not be explained by differences in duration of treatment between groups. Analysis at 1 to 12 weeks, 13 to 24 weeks, and 25 to 36 weeks after initiating treatment indicated higher androgen levels at each time point in the progression group. In addition, the results were not attributable to differing serum levels of aminoglutethimide among responder groups. While the finding of higher androgen levels in the responder group remains unexplained, this study indicates that incomplete estrogen suppression is not responsible for lack of tumor response in patients with progressive disease during amino-glutethimide-hydrocortisone therapy.

Adrenalectomy↗
PubMed1982

Phase I study of a 5-day schedule of mitoxantrone (dihydroxyanthracenedione).

Mitoxantrone (1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione dihydrochloride) in animal studies appears to have a mechanism of action and broad antitumor spectrum similar to the anthracyclines and in preliminary animal studies is without cardiotoxicity. To determine the maximally tolerated dose, mitoxantrone was given to 25 patients with various advanced solid tumors. Sixteen patients had received prior doxorubicin and/or lomustine (CCNU). Myelosuppression was the major toxic effect. All 13 patients who received mitoxantrone doses greater than or equal to 2.73 mg/m2 x 5 days experienced moderate (2000--3000 cells/mm3) or severe (less than 2000 cells/mm3) leukopenia. Thrombocytopenia was also encountered in three of these 13 patients (severe in one, less than 50,000 cells/mm3). At dose levels less than 2.73 mg/m2 x 5 days, myelosuppression was seen in four of 12 patients (three with mild leukopenia and one with mild thrombocytopenia). The blood cell count nadir occurred at 10 days and full recovery occurred by Day 21. Minor clinically insignificant ECG changes occurred in five patients. Minor and transient antitumor effects were seen in five patients. The maximum tolerated dose of mitoxantrone over a 5-day course is 2.73 mg/m2, with leukopenia being the limiting toxic effect.

Adult↗
PubMed1981

A randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer.

We randomized 96 postmenopausal women with metastatic breast carcinoma to receive surgical adrenalectomy or medical therapy with an adrenal inhibitor, aminoglutethimide (AG), plus replacement hydrocortisone. Before randomization, women were stratified according to disease-free interval, site of dominant disease, and estrogen-receptor status. Of 40 evaluable women treated with AG and hydrocortisone, 53 per cent had objective responses, as compared with 45 per cent of 29 women undergoing surgical adrenalectomy (P value not significant). Responses lasted a mean of 17.2 months in the medical group and greater than 17.1 months in the surgical group (not significant). Estrogen levels fell similarly in response to either treatment, whereas AG and hydrocortisone preserved androgen production. A null hypothesis tested the single question asked by this study: "Is surgical adrenalectomy superior to treatment with AG and hydrocortisone?" Rejection at significance levels of P = 0.01 and P = 0.07 for differences of 20 per cent and 10 per cent, respectively, suggested that medical therapy with AG and hydrocortisone may be logically chosen in place of surgical adrenalectomy.

Adrenalectomy↗
PubMed1981

Glycoproteins and human cancer: II. Correlation between circulating level and disease status.

Many cancer patients have elevated serum protein and sialic acid (N-acetyl neuraminic acid, NANA) levels. Serial determinations were performed, using serum treated with perchloric acid from 34 patients with widespread metastatic disease. Six of six patients who underwent debulking surgery had a drop in their serum NANA value to normal levels following a transient rise in the immediate postoperative period. Twenty-eight patients received chemotherapy and had serial NANA determinations over periods ranging from 4 to 12 months. Eleven of 28 patients demonstrated tumor regression or stable disease. Ten of the 11 in this group had a drop in their serum NANA level. The remaining 17 patients showed tumor progression, and serum NANA rose in 11 of 12 patients with widespread progression of metastatic disease. This elevation preceded clinical relapse in 8 of the 11 patients. Elevation did not occur in four of five patients with a local site relapse of disease (two chest wall, one lung mass, one brain metastases). Serial serum glycoprotein titers deserve further consideration as a monitor of response to chemotherapy of metastatic disease.

Antineoplastic Agents↗
PubMed1981

A mitogenic factor for transformed fibroblasts from human platelets.

Human platelets contain discrete glycoproteins that promote the growth of 3T3 (platelet-derived growth factor 1) and SV3T3 (platelet-derived growth factor 2) cells. The factor that promotes the growth of SV3T3 cells is a heat-labile nondialyzable glycoprotein with an isoelectric point of 7.8 to 8.3.

Animals↗
PubMed1980

Influence of estrogen receptor status on response of metastatic breast cancer to aminoglutethimide therapy.

Aminoglutethimide (AG) is an effective chemical ablative form of therapy for metastatic breast cancer in postmenopausal women. Estrogen receptor (ER) status in breast cancer is useful in predicting the response to the hormonal treatments. Of 134 postmenopausal metastatic breast cancer patients treated with AG, ER analysis was done in 63 patients, 52 of whom are now evaluable. ER biopsy was performed prior to Ag therapy in 61 patients, but the results were not known to the investigators. ER value greater than or equal to 10 fmol/mg cytosol protein was considered ER positive (ER+), 4-9.9 fmol/mg borderline, and less than 4 fmol/mg ER negative (ER-). In 38 ER+ patients, objective response rate was 50% (three complete response, 16 partial response) and eight stabilization. Median duration of objective response was 15 months. Forty-three percent of the patients with borderline estrogen receptor level responded objectively (three partial response) with the median duration of response eleven months. Fourteen percent of ER- patients responded objectively (one complete response). Hence the estrogen receptor level predicts response in ER+ and ER borderline patients treated with AG.

Aminoglutethimide↗
PubMed1979

Glycoproteins and human cancer. 1. Circulating levels in cancer serum.

Total protein and sialic acid levels were determined in the supernatant of serum treated with perchloric acid. Patients with either localized or advanced metastatic malignancy have significantly elevated mean serum values. The highest levels occur in patients with lung, GI, GYN cancer, lymphoma and malignant melanoma. Patients with leukemia and multiple myeloma have slightly elevated values, but they were not significantly different from normal. Patients following curative surgery have normal values while patients in clinical remission following chemotherapy have elevated mean serum protein and NANA levels. Elevated values also occur in patients with benign tumors and 12% of patients with nonmalignant disease. Tumor cells appear to shed macromolecules which contribute to the observed elevation of serum protein and sialic acid levels.

Adult↗
PubMed1979

A comparative trial of transsphenoidal hypophysectomy and estrogen suppression with aminoglutethimide in advanced breast cancer.

We compared two treatment regimens, transsphenoidal hypophysectomy and estrogen suppression with aminoglutethimide in women with metastatic breast carcinoma. Three of fourteen patients experienced partial objective tumor regression with a median duration of 4.6 months following hypophysectomy, whereas 10 of 21 women receiving aminoglutethimide responded (2 complete, 8 partial) with a median duration of 11.5 months. Side effects in the medical group were minimal while surgical complications included 2 cases of CSF rhinorrhea, one leading to meningitis and death. In patients receiving aminoglutethimide, urinary free cortisol and plasma dehydroepiandrosterone sulfate fell significantly as did plasma estrone and estradiol. In the hypophysectomy group, anterior-pituitary function testing postoperatively revealed adequate suppression of gonadotropin and prolactin secretion but incomplete inhibition of the ACTH-cortisol axis in 4 of 7 surgical patients studied. Five patients initially treated with hypophysectomy experienced a further reduction of plasma (and urinary) estrone and estradiol levels when given aminoglutethimide. We conclude that estrogen suppression therapy with aminoglutethimide is a feasible alternative to surgical hypophysectomy in providing endocrine suppression and palliation in advanced breast carcinoma.

Adult↗
PubMed1979

A growth factor from spinal cord.

Mitogenic activity is present at a variety of sites in the central nervous system. A growth factor was purified from neonatal bovine spinal cord. It has a pI of 9.5-9.8 and a molecular weight of about 11,000 daltons. Spinal cord growth factor is a basic polypeptide that is inactivated by extremely acid or basic conditions. Its mobility on SDS polyacrylamide gels suggests that this factor is different from pituitary FGF and brain FGF-1.

Animals↗
PubMed1979

Comparison of DES vs DES + chlorambucil in women with first recurrence of breast cancer.

Thirty-four women with first recurrence of breast cancer were randomized into two groups, and received either Diethylstilbestrol (DES) 5 mg orally (PO) t.i.d. alone, or in combination with Chlorambucil (CB) 0.1--0.2 mg/kg/day PO. All patients randomized were greater than 5 years postmenopausal at the time of the study and had no prior chemical or hormonal therapy. Estrogen receptors were not available. There was no significant difference between Groups A and B with respect to frequency of objective response or mean duration of that response, with the values for Group A being 46.2% and 4.8 months, respectively, and for Group B, 46.7% and 4.8 months (P greater than 0.05). The most common toxicities noted for both groups were nausea and vomiting, edema, weakness, and thrombophlebitis. The risk of major toxicity necessitating withdrawal from the study was greater in Group B due to the added danger of thrombocytopenia/pancytopenia. The addition of CB to DES does not appear to offer any significant advantage over DES alone in women with first recurrence of breast cancer.

Aged↗