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Biomedical subjects

G Hortobagyi

Publications and source records attributed to G Hortobagyi.

53 records · Page 3Linked to original sources
PubMed1989

SIS/PDGF-B expression in benign and malignant human breast lesions.

Northern blots with poly(A)-selected RNAs were prepared from four primary human breast carcinomas and hybridized with a SIS/PDGF-B gene probe. High expression of a normal-sized 3.7 kb SIS/PDGF-B transcript was observed in three samples. These three carcinomas were all T3 (greater than 5 cm) lesions and were histologically infiltrating ductal carcinomas accompanied by moderate to marked desmoplasia. Furthermore in situ hybridization with photobiotinylated probes was performed and demonstrated that the SIS/PDGF-B expression was localized within the epithelial cells of malignant as well as benign lesions. It is possible that SIS/PDGFB expression within the epithelial cell components of nonmalignant as well as malignant breast lesions may be in part responsible for the stromal reaction.

Blotting, Northern↗
PubMed1988

Phase II evaluation of Ly156758 in metastatic breast cancer.

Fourteen patients with disseminated breast cancer with primary or secondary resistance to tamoxifen were treated with LY156758. There were no complete or partial responses and 1 patient showed a minor response. These data illustrate that LY156758 did not have significant antitumor activity in patients previously treated with tamoxifen therapy.

Breast Neoplasms↗
PubMed1986

Chemosensitivities of human clonogenic breast tumor cells.

We developed an in vitro system for the testing of the inherent chemosensitivity of clonogenic tumor cells, and we applied the system to the evaluation of 104 human breast tumors. We observed the following: clonogenic breast tumor cells were more sensitive to 4-hydroperoxy-cyclophosphamide (a metabolite of cyclophosphamide with in vitro activity) than to 5-fluorouracil and to doxorubicin (the other two agents used in the frontline treatment of breast carcinoma). The sensitivity of these clonogenic breast tumor cells for mitoxantrone, bisantrene, 4'-epi-doxorubicin, and VP-16 was similar to that for doxorubicin and 5-fluorouracil, but it was less for cis-platinum. In vivo exposure to a combination of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) did not change the sensitivity of cells towards 5-fluorouracil and doxorubicin, but lessened the sensitivity of some cells towards 4-hydroperoxycyclophosphamide. Furthermore, in vivo exposure to doxorubicin did not influence the sensitivity of cells towards the anthraquinone derivatives, 4'-epi-doxorubicin, mitoxantrone, and bisantrene. A comparison of the in vitro and in vivo chemosensitivity revealed that the assayed cell populations were biologically relevant: the concordance of sensitivity on 41 tumors was 68%, or 95%, if the in vitro sensitivity score was adjusted to the tumor bulk. We conclude that our system provides a valid tool to determine the inherent chemosensitivity pattern of the individual tumor types, and to compare the tumor cytotoxic potential of drugs.

Antineoplastic Agents↗
PubMed1986

Use of growth-stimulatory hormones to improve the in vitro therapeutic index of doxorubicin for human breast tumors.

Tumor-specific growth factors that increase the proliferative rate of tumor cells should, in theory, enhance the efficacy of cytotoxic drugs that have cell-cycle-dependent activity. To test this hypothesis, we measured the cytotoxicity of doxorubicin for clonogenic breast tumor cells in the presence and the absence of hormones that stimulate their in vitro growth (17 beta-estradiol, epidermal growth factor, hydrocortisone, and insulin). These growth factors increased the sensitivity to doxorubicin of the clonogenic cell populations from 20 of 25 breast tumors. Their effect was greatest on tumors from hormone-responsive patients. In contrast, these hormones increased the clonogenicity and sensitivity to doxorubicin of bone marrow progenitor cells to a much lesser degree. Hence, under the effect of these growth factors, the in vitro therapeutic index of doxorubicin improved for most of the tumors tested, while tamoxifen citrate, a tumor growth-inhibitory hormone, had the opposite effect. We conclude that tumor tissue-specific growth-stimulatory hormones can improve the in vitro efficacy of cell cycle-active anticancer drugs.

Bone Marrow↗
PubMed1985

Ticarcillin plus clavulanic acid in the treatment of patients with cancer.

Since the combination of ticarcillin with clavulanic acid is active against many otherwise resistant organisms that commonly affect patients with cancer, a therapeutic trial with ticarcillin disodium plus clavulanate potassium for treating infections in cancer patients was conducted. A total of 127 evaluable patients were treated with this antibiotic. Of these, 63 percent were women with breast carcinoma, 28 percent were patients with leukemia, and the remainder were patients with sarcomas and lung cancer. The median duration of therapy was 7.7 days. There were 63 documented infections, with bacteriologic documentation in 39 episodes. Because of the high incidence of gram-positive infections and after the failure of ticarcillin plus clavulanate potassium in two of these episodes, vancomycin was added to the regimen. The overall response rate was 75 percent. In microbiologically proved infections, the response rate was 79 percent. Thirteen of 17 gram-negative infections responded (76 percent), including four of four episodes caused by Pseudomonas aeruginosa. The only failures in this group were two episodes with Klebsiella species, one episode with Escherichia coli, and one episode with Enterobacter species. Of the gram-positive infections treated without vancomycin, five of eight (63 percent) responded and only two episodes due to Staphylococcus aureus and one due to JK diphtheroid bacteria failed. All episodes treated with the combination of ticarcillin plus clavulanate potassium and vancomycin responded. Seven of eight (88 percent) polymicrobial infections and 73 percent of those infections without identified organisms responded as well. The overall response rates for septicemia, pneumonia, soft tissue infections, and urinary tract infections were 71, 50, 71, and 83 percent, respectively. Of five microbiologically proved superinfections, three were fungal, and one each was due to Klebsiella species and S. aureus. No toxicity was observed. For 12 organisms, the minimal inhibitory concentration was lower for ticarcillin plus clavulanate potassium than for ticarcillin alone; in six it was identical. Five organisms were resistant to both, and three that were resistant to ticarcillin were sensitive to ticarcillin plus clavulanate potassium. Ticarcillin plus clavulanate potassium is a safe drug with an expanded spectrum of activity. More therapeutic trials need to be conducted to better define its role in the therapy of serious infections in cancer patients.

Adolescent↗
PubMed1984

Carminomycin. A new anthracycline analog in the treatment of advanced breast cancer.

Twenty-two patients who had metastatic breast cancer previously treated with combination chemotherapy, cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or CMF with vincristine and prednisone, were treated with Carminomycin (carubicin) 20 mg/m2 body surface area by intravenous bolus injection once every 3 weeks. Of 21 evaluable patients, 1 patient achieved complete remission, 5 patients achieved partial responses, and 11 remained stable. Cases of acute drug toxicity included myelosuppression, phlebitis, and gastrointestinal symptoms; there were four cases of mild alopecia, which consisted of thinning of the scalp hair. There were three cases of biopsy-proven cardiomyopathy, contrary to previous reports from the United Soviet Socialist Republic, which indicated that this drug was relatively free of cardiotoxicity. The median duration of remission for responders was 23 weeks. It is believed that Carminomycin has significant activity against metastatic breast cancer and, because its side effects, especially nausea, vomiting, and alopecia, were considerably milder than those experienced with Adriamycin, further investigation of this drug is warranted.

Adult↗
PubMed1984

Improved culture conditions for clonogenic growth of primary human breast tumours.

Four established human breast tumour cell lines with different biologic properties were selected for study and requirements for their clonogenic growth in semisolid cultures were identified. The conventional conditions were modified by factors that enhanced colony formation of 3 or more of these cell lines. The modified culture conditions were then applied to the growth in agar of primary breast tumours. A 5-fold improvement in plating efficiency was observed when cultures of 105 primary tumours grown under these modified conditions were compared to those of 52 tumours grown earlier under conventional conditions, and a 4-fold improvement resulted from the addition of hormones and conditioned medidum in 26 tumours cultured simultaneously under both conditions. The biologic relevance of these clonogens recovered in vitro was substantiated by a 70% concordance of in vitro and in vivo tumour sensitivity to anticancer drugs.

Agar↗
PubMed1983

A phase I-II study of continuous 5-day infusion mitomycin-C.

A phase I-II study was undertaken to establish the maximum-tolerated dose of a continuous 5-day infusion of mitomycin-C and its efficacy in patients with advanced metastatic drug-resistant breast and gastrointestinal malignancies. The dose-limiting toxicity was myelosuppression, predominantly thrombocytopenia, and was severe and cumulative. Nonhematologic toxicity was infrequent, and no renal or cardiac toxicity was seen. For patients with breast cancer who had received extensive prior therapy, 3 mg/m2/day for 5 days repeated every 6-8 weeks were well-tolerated doses; and for patients with gastrointestinal cancer, the maximum-tolerated dose was 4 mg/m2/day. One patient with breast cancer had a partial response lasting 4 months, and no responses were observed in patients with gastrointestinal cancer. The administration of mitomycin-C by continuous infusion did not appear to have improved its therapeutic index.

Aged↗
PubMed1983

Hormonal therapy for metastatic male breast cancer.

Forty-one men with metastatic breast cancer were treated with 70 trials of hormone therapy. These included 25 orchiectomies and 45 additive hormonal treatments. The overall response rate was 31%. The response rate was 32% to orchiectomy, 17% to estrogens, 43% to steroids, 25% to tamoxifen citrate, and 60% to androgens. The response to additive hormonal therapy was 31% and was not affected by prior orchiectomy (33% v 30%). Median overall response duration was 12 months, 17.5 months following orchiectomy, 8.5 months following additive hormonal therapy, five months following estrogens, 11 months following steroids, and eight months following androgens. Median survival from first metastasis was significantly prolonged in patients responding to orchiectomy and additive hormonal therapy. Patients with a disease-free interval (DFI) longer than 12 months had a 59% response rate to hormonal therapy compared with 9% of those with a DFI no more than 12 months. Response to one form of hormonal therapy did not predict later hormonal response. Ablative and additive hormonal therapy offer effective palliation to one third of male breast cancer patients, produce little toxic effects and morbidity, and improve survival duration after metastasis in responders.

Adrenal Cortex Hormones↗
PubMed1976

Chemoimmunotherapy of advanced breast cancer: prolongation of remission and survival with BCG.

Forty-five patients with disseminated breast cancer were given a trial of combination chemotherapy consisting of fluorouracil, adriamycin, and cyclophosphamide (FAC) and immunotherapy with BCG given by scarification. The results were compared with those in a comparable group of 44 patients treated with FAC alone immediately before the chemoimmunotherapy study. The remission rates (73% and 76% for FAC and FAC-BCG respectively) were similar in both studies. The durations of remission for patients on FAC-BCG (medium 12 months) were longer than remissions achieved for patients given FAC alone (median 8 months) (P = 0.068). The most notable effect of BCG was on survival. Thus 21 out of 34 patients achieving remission on FAC-BCG were alive at the time of the last follow-up examination (median over 22 months) compared with 11 out of 32 patients achieving remission on FAC (median 15 months) (P = 0.01). Twenty-six of the 45 patients given FAC-BCG were alive at the time of the last follow-up examination (median over 22 months) compared with 12 of the 44 patients given FAC (median 15 months) (P = 0.005). Although the apparent benefit of BCG could be explained by a maldistribution of some prognostic factors, the data suggest that further trial of chemoimmunotherapy of breast cancer should be carried out.

Adult↗
PubMedDate not supplied

The breast self-examination practices of high risk women: implications for patient education.

The breast self-examination (BSE) behavior of 142 women referred to a large cancer center with malignant or benign breast disease was investigated. The women were interviewed about their BSE practices and variables that may have influenced their BSE behavior. Those reporting prior BSE practice were asked to demonstrate their breast examination to a trained nurse, who rated their performance against a set of standard criteria. Although it might be assumed that these women have had more opportunity to become educated about BSE, results showed the ratings of the women's performances were uniformly poor. Less than half reported having formal instruction by a medical professional. This is of particular consequence considering that those women taught by a doctor or nurse performed significantly more BSE steps than did those taught in other ways. Women who were encouraged to do BSE by friends or relatives also performed significantly more steps. Based on the study findings, specific recommendations are made, which can be applied to the improvement of BSE educational programs.

Attitude to Health↗