Virologic and immunologic parameters that predict clinical response of AIDS-associated Kaposi's sarcoma to highly active antiretroviral therapy.

The purpose of the work was to assess the predictive value of biologic factors on the efficacy of highly active antiretroviral therapy alone or combined with chemotherapy on AIDS-associated Kaposi's sarcoma. Twenty-six AIDS-Kaposi's sarcoma patients who started therapy with protease inhibitors were investigated. No baseline chemotherapy was associated with less severe initial clinical status.

Parathyroid hormone-related peptide stimulates proliferation of highly tumorigenic human SV40-immortalized breast epithelial cells.

Parathyroid hormone-related protein (PTHrP) is the main mediator of humoral hypercalcemia of malignancy (HHM) and it is produced by many tumors, including breast cancers. Breast epithelial cells as well as breast cancer tumors and cell lines have been reported as expressing PTHrP and the PTH/PTHrP receptor, suggesting that PTHrP may act as an autocrine factor influencing proliferation or differentiation of these cell types. We investigated PTHrP gene expression, PTH/PTHrP receptor signaling, and PTHrP-induced mitogenesis in three immortalized human mammary epithelial cell lines that exhibit differential tumorigenicity.

Antisense expression for amphiregulin suppresses tumorigenicity of a transformed human breast epithelial cell line.

The epidermal growth factor (EFG) family of receptors and their respective ligands play a major role in breast cancer progression and are the targets of new therapeutic approaches. Following immortalization with SV40 T antigen of normal human breast epithelial cells, a transformed variant cell line (NS2T2A1) was selected for its increased tumorigenicity in nude mice. This cell line was shown to have a higher expression of EGF receptors (EGFR) and amphiregulin (AR) when compared to their normal counterparts or less aggressive transformed cells.

Role of epidermal-growth-factor receptor in tumor progression in transformed human mammary epithelial cells.

The presence of epidermal-growth-factor receptors (EGFR) and of its ligands (TGFalpha and amphiregulin) in breast-cancer tissues suggests that they play a paracrine/autocrine role in tumor growth or progression. This hypothesis was tested on 3 cell lines, S2T2, NS2T2A and NS2T2A1. These epithelial cells are derived from a normal human breast-epithelial-cell culture transformed by SV40-T Ag, are of the same clonal origin, have respectively increasing levels of EGFR, TGFalpha, amphiregulin and of thymidine-kinase activity associated with increasing tumorigenic potential in nude mice (tumor intake and tumor volume).

Somatostatin receptors in prostate tissues and derived cell cultures, and the in vitro growth inhibitory effect of BIM-23014 analog.

We investigated somatostatin receptors (SSTRs) in surgical specimens of prostate cancer and benign prostate hyperplasia (BPH), a normal immortalized epithelial cell line (PNT1), epithelial cancer cell lines, and stromal cells in short-term culture derived from normal and BPH biopsies. Cross-linking studies with 125I-Tyr11-SRIF-14 (125I-SRIF) and the SRIF analog 125I-BIM-23104 identified one major 57-kDa band both in surgical specimens and in epithelial and stromal cells cultures. In membrane-enriched fractions and whole stromal cells from a normal prostate and from one BPH, a single type of SSTR was characterized (Kd = 6.

Recurrent cytogenetic alterations of prostate carcinoma and amplification of c-myc or epidermal growth factor receptor in subclones of immortalized PNT1 human prostate epithelial cell line.

To develop an experimental prostate cancer model, we immortalized normal human prostate adult epithelial cells with SV40 large-T antigen. Two sublines were derived in culture, namely PNT1A and PNT1B. They retained the characteristics of prostate epithelial cells, but did not clone in soft agarose.

EGF modulation of the ras-related rhoB gene expression in human breast-cancer cell lines.

The mRNA levels of the ras-related human rhoA, rhoB and rhoC genes were studied in human breast-cancer cell lines (HBCal), and in normal and immortalized mammary epithelial cells (HMEC) by Northern blot analysis and in situ hybridization. In contrast to the ubiquitous rhoA and rhoC gene expression, dramatic variations in the mRNA level of the rhoB gene were evidenced. The rhoB mRNA level appeared to be inversely correlated to the amounts of the epidermal-growth-factor(EGF) receptors in these cells.

Cell and membrane lipid analysis by proton magnetic resonance spectroscopy in five breast cancer cell lines.

The lipid composition of five human breast cancer cell lines (MCF-7, T47D, ZR-75-1, SKBR3 and MDA-MB231) was assessed by proton magnetic resonance spectroscopy (MRS) in whole cells and membrane-enriched fractions. The proportions of the three main lipid resonances in 1D spectra were different for each cell line. These resonances included mobile methyl and methylene functions from fatty acids of triglycerides and phospholipids and N-trimethyl from choline of phospholipids.

Modulation of proliferation, estradiol receptors and estrogen regulated protein PS2/BCEI in human breast cancer cell lines by gamma interferon.

The effects of recombinant gamma interferon (IFN gamma) on proliferation, estrogen-receptor (ER) content, mRNA level and protein secretion of a breast cancer estrogen-induced protein pS2/BCEI were investigated in two human breast cancer cell lines, ZR75-1 and T47D. Both cell lines have estrogen and progesterone receptors and previously showed HLA class I and class II responses to IFN gamma (Int J Cancer 1990; 45: 1169). An antiproliferative effect of IFN gamma (1000-5000 U/ml) was observed in serum containing medium on ZR75-1 but not on T47D cells.

P-glycoprotein expression and in vitro reversion of doxorubicin resistance by verapamil in clinical specimens from acute leukaemia and myeloma.

The expression of the P-glycoprotein which is associated with the development of multidrug resistance in various cell lines was investigated in 87 fresh acute leukaemia and multiple myeloma samples using the specific mouse monoclonal antibody MRK16 in an indirect immunofluorescence assay. Considering a 10% positive cell cut-off value, a heterogeneous expression of P-glycoprotein was observed in 5/22 (22.7%) de novo acute leukaemias, 7/22 (31.

[Lipid profiles of breast cancer cell lines: proton nuclear magnetic resonance spectroscopy].

Nuclear magnetic resonance spectroscopy was performed on breast cancer cell lines MCF-7, MDA-MB231 and T47D. Proton spectra showed discrepancies of lipid quantity in the different lines. The high resolution lines of lipids were not as intense in the membrane preparations.

Characterization, in some human breast cancer cell lines, of gastrin-releasing peptide-like receptors which are absent in normal breast epithelial cells.

The binding of 125I-Tyr4 bombesin was investigated on plasma membranes of 8 human breast cancer cell lines and 2 long-term cultures of normal human breast epithelial cells. Scatchard plots were compatible with high-affinity, single-site class of receptors in 3 cell lines (KD of 0.75 x 10(-9) and 10(-9) M, Bmax of 0.

Quantitative modifications of major histocompatibility complex (MHC) antigens induced by recombinant gamma interferon in two human breast cancer lines.

H466-B and T47-D breast carcinoma cell lines were treated with recombinant gamma interferon (r gamma IFN) to study major histocompatibility complex (MHC) class I and class II antigen responses. Untreated H466-B cells released B2 microglobulin (B2M) into the culture medium and expressed B2M and class I heavy chain on 100% of the cells. The expression of class II antigens (DR) was limited to 8 +/- 4% of the cells.

1,25-Dihydroxycholecalciferol induces an increase in PGE1- and forskolin-stimulated cyclic-AMP production in T47D human breast cancer cell line.

The effect of 1,25-dihydroxycholecalciferol [1,25(OH)2D3], the active form of vitamin D3, on cell growth, clonogenicity, and cyclic adenosine monophosphate (cAMP) production was examined in human breast cancer cell line T47D. 1,25(OH)2D3 markedly inhibited proliferation of T47D cells in a time- and concentration-dependent manner. 1,25(OH)2D3 5 X 10(-7) reduced to 70% [3H]thymidine incorporation into DNA.

[Calcium antagonists and glycoregulation: dissociated effects of nicardipine on vascular tonus and insulin secretion].

Insulin release is coupled with a calcium entry into the pancreatic B cells. The use of calcium-antagonists may eventually alter glucose homeostasis. To evaluate this possibility, nicardipine action was tested both in vitro and in vivo: 1.

[Effects of nifedipine on carbohydrate metabolism in the non-insulin dependent diabetic].

The aim of this prospective, randomized, double-blind, placebo controlled study was to investigate the effect of nifedipine on carbohydrate metabolism in diabetic patients after a 3-day and a 3-month course of treatment. Sixteen non obese, well controlled non-insulin dependent diabetics, (HbA1 less than 10%), with moderate untreated hypertension were divided in two groups: nifedipine (group N, 8 patients) and placebo (group P, 8 patients). An oral glucose tolerance test (OGTT, 75 g glucose) and an arginine infusion were performed before, after a 3-day, and a 3-month course, either of nifedipine 30 mg/D or placebo.

Binding of 125I-insulin to the human histiocytic lymphoma cell line U-937: effect of differentiation with retinoic acid.

The human histiocytic lymphoma line U-937 consists of cells having characters of immature monocytes. We have demonstrated that these cells possess highly specific insulin receptors with binding properties similar to that found for mature human blood monocytes. 125I-insulin binding increased progressively with time to reach a maximum at 90 min at 22 degrees C and was proportional to the number of cells in the incubation medium.

[Effect of long-term administration of clonidine on growth hormone secretion in hypertensive diabetics].

The anti-hypertensive effect of clonidine is closely related to its central alpha-agonist action. In acute administration, the drug provokes a significant increase in the plasma concentrations of growth hormone (GH). In chronic administration, the effects of clonidine on GH secretion are not well documented.

Rapid identification of diabetic patients with essential hypertension sensitive to acebutolol.

The antihypertensive effect of 2,000 mg of acebutolol investigated with an acute 48 hr test in 60 diabetic and 60 non-diabetic in-patients with essential hypertension. In hypertensive diabetic patients, acebutolol was induced a significant fall in blood pressure similar to that observed in non-diabetics. The acute antihypertensive effect of acebutolol was not uniform in hypertensive subjects: a significant decrease of blood pressure was observed in 34 diabetics and 31 non-diabetic patients.

[The effects of acebutolol on endocrine and metabolic reactions induced by acute hypoglycaemia. Study in normal subjects and in insulin-dependent diabetics (author's transl)].

Six normal subjects and six normotensive insulin-dependent diabetics underwent two insulin hypoglycaemia tests after administration for three days of either a placebo or of acebutolol--a cardioselective beta-blocker--at a dose of 400 mg per day. The order in which the tests were performed was decided by random selection. Acebutolol suppressed the tachycardia which occurred as a reaction to hypoglycaemia but did not interfere with other warning symptoms and signs.

Effect of somatostatin on plasma C-peptide immunoreactivity in normal man.

The effect of somatostatin on plasma C-peptide immunoreactivity was studied in seven normal men following an intravenous 25 g glucose load. No elevation in plasma insulin was observed and similarly no rise in plasma C-peptide immunoreactivity occurred, indicating that somatostatin inhibits glucose-induced C-peptide release as well as insulin release.