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Biomedical subjects

P Marchetti

Publications and source records attributed to P Marchetti.

At least 181 records · Page 10Linked to original sources
PubMed1993

Natural interferon-beta treatment and steroid hormone receptors in primary endometrial cancer.

Forty-three patients with primary endometrial carcinoma were treated with natural interferon-beta (IFN-beta) at two different dose levels (2 x 10(6) IU or 6 x 10(6) IU im 3 times/week for 1 week). IFN-beta increased receptors for estrogens (ER) and progesterone (PR) in a high percentage of the 40 evaluable patients, without modifying the receptor affinity. The ER and PR enhancement, which was simultaneous in at least 50% of patients, and the increase of over 100 fmol/mg protein observed in some cases suggest that IFN-beta exerts a profound influence on receptor expression and, probably, on the hormone sensitivity of the tumor.

Adenocarcinoma↗
PubMed1993

In vitro morpho-functional analysis of pancreatic islets isolated from the domestic chicken.

The technique whereby islets were isolated from the pancreas of chicken and their in vitro histological and functional characterization are described in this paper. Our isolation procedure consisted of two steps: initially the pancreas removed from the chicken was perfused with a 2% solution of collagenase and enzymatic digestion was then carried out using the same solution. After this, density gradient separation was performed on the digested tissue, by means of differing Histopaque solutions: at the end of the separation, the islets were studied by light microscopy after treatment with diphenylthiocarbazone, which selectively stains beta-cells, and by scanning and transmission electron microscopy. The results reported here show the pattern closely resembled that encountered when islets were studied in situ. The beta-cells of the islets proved in vitro to preserve their functional capability of producing insulin even after stimulation with glucose or arginine.

Animals↗
PubMed1993

Steroid receptor enhancement by natural interferon-beta in advanced breast cancer.

In the current study we investigated the effect of two different doses of natural interferon-beta (IFN-beta) on steroid hormone receptors in 45 patients with advanced breast cancer. IFN-beta seems to regulate the receptor mechanisms, inducing in cutaneous metastases an increase of oestrogen and progesterone receptors. Moreover, using IFN-beta and tamoxifen as a combined therapy in 23 receptor-positive patients, no negative interference of the two drugs was observed and no relevant side-effects due to the treatment were noticed. The modulation of steroid receptor content by IFN-beta in advanced breast cancer might represent an interesting way to ameliorate the clinical responsiveness to anti-oestrogens.

Aged↗
PubMed1992

Structure-activity relationship in the mutagenic effect of chiral or racemic 2-bromo-propanamides on Salmonella typhimurium.

Some 2-bromo-propanamides were prepared and tested for direct mutagenicity in Salmonella typhimurium TA 100. Results confirm the mutagenic activity of 2-bromo-N-benzyl-propanamide and indicate that it is independent of enantiomeric configuration. A variation in the chemical structure, namely, the addition of a methyl group at the benzylic carbon, causes the four resulting diastereomers to be devoid of any activity. Conversely, some racemic ring-substituted methoxy and/or hydroxy derivatives of the parent compound displayed mutagenic properties, causing an increase in the number of his+ revertants up to 524 per milligram per plate.

Amides↗
PubMed1992

The effect of transplantation site and islet mass on long-term survival and metabolic and hormonal function of canine purified islet autografts.

Determination of the long-term function of islet transplantation in relation to the implantation site and the numbers of islets is of scientific interest and, with human islet transplant trials in progress, is a pressing clinical question. In this study, highly purified canine islets were isolated by collagenase digestion and Ficoll purification, and autotransplanted into either the spleen (in 10 dogs) or the liver (in 12 dogs). Dogs transplanted with islets into the spleen or liver received 264,300 +/- 20,300 (mean +/- SEM) and 158,600 +/- 15,000 islet equivalents (150-microns-sized islets) respectively. Graft survival at 1 yr was 86% in intrasplenic islet autografts (ISTx) and 50% in intraportal islet autografts (IPTx). Intravenous glucose tolerance tests and mixed meal-oral glucose tests were performed 1-12 mo from islet transplantation. Compared to controls, ISTx and IPTx dogs showed a similar decrease of glucose tolerance after both intravenous glucose tolerance tests and mixed meal-oral glucose tests. On intravenous glucose tolerance tests, plasma insulin levels were lower in ISTx than in IPTx dogs and controls. On mixed meal-oral glucose tests, insulin values were higher in IPTx dogs than in controls. There was a positive correlation (r = .56, p < 0.05) between the number of transplanted islet equivalents and the K values. These results demonstrate that, in dogs with islet transplant: 1) long-term islet survival can be achieved in the spleen better than in the liver; 2) islet survival is related to the mass of transplanted islets in the spleen, but not in the liver, where other factors probably affect islet survival; 3) the ability of metabolizing glucose is reduced after both intrasplenic and intraportal islet autografts; 4) both reduced insulin secretion (predominant in ISTx dogs on intravenous glucose tolerance testing) and insulin resistance (predominant in IPTx dogs on mixed meal-oral glucose tests) are the probable causes of the decreased glucose tolerance.

Animals↗
PubMed1992

Recombinant interferon-alpha 2b affects proliferation, steroid receptors and sensitivity to tamoxifen of cultured breast cancer cells (CG-5).

Exposure of CG-5 human breast cancer cells to recombinant interferon (IFN)-alpha 2b results in a significative inhibition of cell proliferation; this is observed when cells are cultured in their standard conditions and is not modified if serum concentration present in the culture medium is lowered. Estrogen receptors are increased in CG-5 cells following a 5 day treatment with concentrations of IFN-alpha 2b ranging from 10 to 1000 IU/ml of culture medium. Progesterone receptors seem to be more influenced by a longer treatment with the drug (7 days). The Kd of both receptors is not modified by the exposure of cells to IFN-alpha 2b. Finally, the antiproliferative effect of tamoxifen on CG-5 cells is amplified by the simultaneous addition to culture medium of IFN-alpha 2b even at very low concentrations.

Breast Neoplasms↗
PubMed1992

Effects of cyclosporine on insulin secretion and insulin sensitivity in dogs with intrasplenic islet autotransplants.

Concern about cyclosporine causing adverse effects on glucose metabolism is based mainly on in vitro studies and in vivo data in rodents. However, data on large mammals and humans are much more controversial. Because the drug is used as therapy accompanying pancreatic or isolated islet transplantations, studies in large animals are needed to assess whether cyclosporine inhibits beta-cell function and causes glucose intolerance. To address these issues, we examined intravenous glucose tolerance, islet beta-cell function, and insulin sensitivity in a group of adult mongrel dogs with intrasplenic islet autografts, with and without cyclosporine treatment. Similar fasting plasma glucose and insulin values were found before and after pancreatectomy and islet transplantation. After intravenous glucose, plasma glucose values decreased more slowly in dogs that had undergone transplantation, but no additional adverse effect as a result of cyclosporine was observed. During euglycemic clamp studies, performed at both physiologic and pharmacologic insulin concentrations, the drug had no effect on the total amount of metabolized glucose, and glucose production was unaffected by cyclosporine treatment. Thus intramuscular cyclosporine therapy does not seem to inhibit insulin secretion from heterotopic islets or to affect peripheral and hepatic insulin sensitivity in dogs with intrasplenic islet autografts.

Animals↗
PubMed1991

Results of our first nine intraportal islet allografts in type 1, insulin-dependent diabetic patients.

With the first demonstration of insulin independence following intraportal islet transplantation into a patient with type 1 diabetes, a new era of clinical islet transplantation will begin. This report provides our initial experience of clinical islet transplantation with a total of nine consecutive portal vein islet transplants in seven diabetic recipients. The first three transplants were done in nonrenal failure diabetics (NRFI) using 6319 +/- 2173 islets/kg body weight with islets processed from single pancreas and cultured for 7 days at 24 degrees C. Prednisone, azathioprine, and cyclosporine were initiated prior to transplant. While all three recipients demonstrated C-peptide function posttransplant, all three rejected their grafts at 2 weeks. Five days of OKT3 treatment failed to recover more than 10% of their rejecting islet grafts. The studies were then shifted to established kidney transplant recipients (EKI) maintaining their basal immunosuppression while adding 7 days of Minnesota antilymphoblast globulin (MALG) to the recipient using islets from single donor pancreas that had been cultured for 7 days at 24 degrees C. There were an average of 6161 +/- 911 islets transplanted intraportally into three EKI recipients. All three had C-peptide response from the transplant, but none achieved insulin independence. While the first patient rejected his graft at 2 weeks, two recipients demonstrated long-term islet function up to 10 months posttransplant. Sustacal challenge testing demonstrated C-peptide responsiveness, but in a delayed pattern suggesting insufficient islet mass had been transplanted. The next three kidney transplant recipients received islets from more than one donor pancreas averaging 13,916 +/- 556 islets/kg body weight. The first of these was the first to achieve insulin independence from 10 to day 25 posttransplant when she appeared to have a rejection episode. The second and third recipients were retransplanted with islets from multiple donors having achieved partial islet function from single pancreas donor. The first patient on triple immunosuppression is demonstrating long-term partial function at 184 days but is not insulin independent. The third patient on prednisone and azathioprine received one half his islets after 7-day culture and the other half after 7-day culture combined with cryopreservation. He is continuing to demonstrate insulin independence for 154 days post-transplant with a glycated hemoglobin value of 5.6%. Sustacal challenge data demonstrate a total stimulated C-peptide response of 155 rhomol/ml at 4 months post-transplant compared with 148 +/- 12 rhomol/ml for normal controls (NC) and 425 rhomol/ml for nondiabetic, established kidney transplant recipients on triple immunosuppression.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Automated large-scale isolation, in vitro function and xenotransplantation of porcine islets of Langerhans.

To evaluate the potential of utilizing porcine islet tissue as an alternative to human islet tissue for transplantation, we developed a method for the isolation of large amounts of highly purified porcine islets, and assessed the in vitro and in vivo function of the isolated islets after 1, 4, and 7 days of culture. The pancreatic duct of the splenic lobe was cannulated and distended by injection of Hanks' balanced salt solution containing 1.5 mg/ml collagenase. The pancreas was then processed by a modification of the automated digestion-filtration method developed in this laboratory, and with purification accomplished by Euro-Ficoll gradients (dialyzed Ficoll in Eurocollins solution), consisting of two layers of 1.108 and 1.091 g/cm3 density, topped with a layer of HBSS. The postpurification yield was 5203 +/- 645 (mean +/- SEM) islets per gram of pancreas with a number of islet equivalents (IE) per gram pancreas (islet equivalence: 150-microns-sized islets) of 3551 +/- 305, and a volume of 6.27 +/- 1.7 mm3 islet tissue per gram of pancreas. The islet purity exceeded 90%. Overnight-cultured, perifused porcine islets released 53.1 +/- 8.2 pM insulin/200 IE at 3.3 mM glucose, and 114.9 +/- 25.4 pM insulin/200 IE at 16.7 mM glucose (P less than 0.001 vs. basal output). When theophylline was added, insulin secretion increased to 264.2 +/- 63.2 pM/200 IE (P less than 0.001 vs. basal secretion and P less than 0.005 vs. secretion at 16.7 mM glucose). After 4 days of culture, the islets still responded to secretagogues. The functional integrity of the isolated islets was confirmed by reversal of diabetes in aL3T4 antibody-treated C57B/B6 diabetic mice: normoglycemia was promptly restored by transplanting 1000 overnight- or 7-day-cultured (24 degrees C) islets under the kidney capsule. These results suggest that continued improvements of porcine islet isolation and culture could permit the use of porcine islets in immunoalteration and immunoisolation studies that may lead to eventual human transplantation.

Animals↗
PubMed1991

Natural beta-interferon and androgen receptors in prostatic cancer cells.

Both PC-3 and DU-145 cell lines are androgen-insensitive, but, in our experience, they contain androgen receptors (AR). Treatment of these cells with natural beta-interferon at a concentration of 1,000 IU/ml of culture medium determines an increase of AR (evaluated by a whole-cell assay), statistically significant with respect to control. Androgen unresponsiveness of our cells could be due to an AR level which is lower than that present in hormone-sensitive prostatic cancer cell lines, such as LNCaP cells. For this reason, interferon-promoted AR increase merits further investigation, even if other defects in receptor mechanism, responsible for hormone insensitivity, cannot be excluded.

Cell Line↗