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Biomedical subjects

M Pollak

Publications and source records attributed to M Pollak.

At least 37 records · Page 2Linked to original sources

The ability of suramin to block CD4-gp120 binding is reversed in the presence of albumin.

We have shown that suramin can directly inhibit the binding of the human immunodeficiency virus type 1 gp120 envelope protein to immobilized CD4, thus helping to explain the previously described antiviral properties of suramin. However, physiological concentrations of serum albumin significantly attenuated suramin's antiviral effects, suggesting that only free suramin has antiviral properties. Reported discrepancies between in vitro and clinical activities of suramin may be due to differences between free suramin levels in experimental assays and those achievable clinically.

Animals

A mathematical model describing consequences of abnormally high levels of epidermal growth factor receptor on the proliferation of neoplastic cells.

Recent laboratory and clinical data suggest that some human neoplasms exhibit unusually high levels of cell-surface receptors for epidermal growth factor, and that this abnormality is associated with rapid cellular proliferation and poor prognosis. We propose that the existence of an abnormally high number of mitogen receptors is not merely correlated with rapid proliferation but is pathophysiologically responsible for such behavior. Cells with high levels of mitogen receptors may be rendered 'hypersensitive' to mitogenic stimuli, and hence may be stimulated to divide even when ambient mitogen concentrations are at a low 'background' level, insufficient to prompt the division of cells with a normal number of receptors. To investigate this hypothesis further, we have developed a mathematical model that describes proliferative behavior of cells as a function of mitogen concentration and receptor number. The model enables us to simulate the proliferative behavior of cells with various receptor levels at various mitogen concentrations and predicts a growth advantage associated with excess mitogen receptors. Computer simulations based on the model are consistent with previously published experimental data. This work provides support for the view that overexpression of genes encoding normal growth factor receptors can contribute to the inappropriate proliferation of neoplastic cells.

Cell Division

Effect of tamoxifen on serum insulinlike growth factor I levels in stage I breast cancer patients.

Insulinlike growth factor I (IGF-I) has been shown to be a potent mitogen for breast cancer cells in vitro, and IGF-I receptors have been demonstrated on human primary breast neoplasms. In a randomized, placebo-controlled study, we document that administration of the antiestrogen tamoxifen to patients with breast cancer was associated with a statistically significant (P = .002) reduction in the serum level of IGF-I. The mean IGF-I level was 1.4 U/mL in the placebo-treated group and 0.9 U/mL in the tamoxifen-treated group. Because serum IGF-I level is growth hormone (GH) dependent and because data suggest that the pubertal surge in GH and IGF-I levels is sex steroid dependent, we speculate that the mechanism underlying our observation may involve blockade by tamoxifen of estrogen action in the hypothalamic-pituitary axis. We conclude that tamoxifen treatment reduces IGF-I levels and that this reduction may contribute to the therapeutic effect of the drug.

Aged

Suramin blockade of insulinlike growth factor I-stimulated proliferation of human osteosarcoma cells.

The polyanionic compound suramin is currently being evaluated for antineoplastic activity. On the basis of previous in vitro studies, it has been suggested that the mechanism of action of suramin may be related to its ability to attenuate the mitogenic effects of peptide growth factors, such as platelet-derived growth factor and epidermal growth factor. We recently reported that MG-63 human osteosarcoma cells are mitogenically responsive to insulinlike growth factor I (IGF-I). We now demonstrate for the first time that suramin interferes with the interaction between IGF-I and its receptor and abolishes in vitro IGF-I-stimulated proliferation of these osteosarcoma cells. The fact that cell proliferation resumes when suramin is removed indicates that this is not a cytotoxic effect. We conclude that IGF-I should be added to the list of growth factors whose bioactivity can be attenuated by suramin and that clinical studies of suramin and its analogues are indicated in IGF-I-receptor-positive malignancies such as osteogenic sarcoma.

Affinity Labels

Mitomycin C and mitoxantrone chemotherapy for advanced breast cancer: efficacy with minimal gastrointestinal toxicity and alopecia.

In an attempt to examine the possibility of decreased toxicity in patients with advanced breast cancer who had not previously received chemotherapy, 33 women were given combination chemotherapy consisting of mitomycin C (10 mg/m2) every 6 weeks and mitoxantrone (6 mg/m2) every 3 weeks. The patients had predominantly visceral disease and received a median of two cycles of therapy. Of the 32 evaluable subjects, 15 (47%) achieved a partial response lasting a median of 7 months. Hematological toxicity was generally mild, although there were two episodes of sepsis. One patient developed hemolytic-uremic syndrome, and one subject developed pulmonary fibrosis, both presumably attributable to treatment with mitomycin C. Another patient died of hepatic failure (hepar lobatum). Thus, there were five patients who sustained life-threatening toxicities; this may have been due to the poor performance status and advanced age of some of the patients. Gastrointestinal toxicity and alopecia were minimal. Patient acceptance was high and there was an improvement in symptomatology in the majority of patients. In conclusion, mitomycin C and mitoxantrone chemotherapy is an active drug combination for the treatment of advanced breast cancer that seldom causes significant distressing gastrointestinal side effects or alopecia; however, the duration of response to this regimen appears to be shorter than that obtained with either cyclophosphamide - methotrexate - 5-fluorouracil (CMF) or cyclophosphamide - Adriamycin - 5-fluorouracil (CAF) combination chemotherapy.

Alkylating Agents

Body size and breast cancer prognosis: a statistical explanation of the discrepancies.

A historical cohort of 68 female breast cancer patients from one institution who were enrolled in a multicenter randomized controlled trial between 1971 and 1973 were followed up to the beginning of 1986. Weight and height at the time of mastectomy were transformed into two indices of body size, namely the Quetelet Index and a weight to "ideal weight" ratio. These two indices were analyzed for their relation with overall and disease-free survival, while controlling for the effect of several potential confounding variables. While neither index was linearly related to the hazard of death or recurrence, a significant quadratic (curvilinear) relation was found for both indices and both hazards. In all cases the hazard function was concave up, indicating that not only overweight but also underweight status is predictive of an unfavorable prognosis of breast cancer. This finding offers a possible explanation for the discrepancies among previous studies on this topic.

Adult

Combination chemotherapy with carboplatin and bleomycin for advanced and recurrent head and neck cancer: a phase II study.

Carboplatin is a platinum analogue with activity reported in head and neck cancer. We conducted a phase II trial with 14 patients who had recurrent head and neck cancer. They were treated with carboplatin 300 mg/m2 intravenously (I.V.) and bleomycin 30 units I.V. every 4 weeks. No responses were observed in this group of patients. Dose intensity of carboplatin administration may be an important determinant of response.

Aged

[Psychosocial consequences of HIV infection].

A questionnaire survey of 103 patients of the Paris Pitié-Salpêtrière Hospital measures the changes in family life, work relations and in sexual behaviour occurring after an HIV infection diagnosis. Most patients choose to keep their diagnosis secret, an attitude that places them into a double bind situation. This silence, chosen as a mean of self-protection, prevents patients from making themselves understood and from mobilising the material and psychological help they need.

Acquired Immunodeficiency Syndrome

[Male homosexuals faced with the AIDS epidemic].

This survey among 1 000 french male homosexuals and bisexuals (July-August 1985) shows the reactions to AIDS in the still largest risk group. The survey reveals the diversity of social and sexual lifestyles. Gays perceive AIDS as a health threat, but also as a social threat eventually leading to discrimination. Ambivalence also prevails in their relationships with medical authorities. This survey allows to draw some conclusions concerning preventive strategies in the gay community.

Acquired Immunodeficiency Syndrome

Housing and mothering: their effects upon the developmental levels of 3-year-old children.

The development of 200 3-year-old children was measured, using Gesell parameters of development. The levels of development were matched against the adequacy, or inadequacy, of maternal care and housing, the scales for which were derived from a questionnaire completed by the children's mothers. Housing was not found to affect the children's developmental levels, while the adequacy of maternal care was highly significantly related to satisfactory child development.

Adult