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Biomedical subjects

M Dicato

Publications and source records attributed to M Dicato.

At least 19 recordsLinked to original sources
PubMed1992

Genetic aspects of multidrug resistance.

Gene amplification is responsible both for dihydrofolate reductase induced methotrexate resistance, and for the P-glycoprotein encoding multigene family induced multidrug resistance. The 6 pairs of hydrophobic regions of the P-glycoprotein fold up in a snake-like structure through the lipidic layers of the cell membrane. Other detoxification mechanisms include the glutathione S-transferase 'pi', but without gene amplification.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

The genetic basis of multidrug resistance.

Cellular multidrug resistance, a common side-effect of anticancer chemotherapy frequently leading to failure of the treatment, has been characterized as an acquired resistance to several antimitotic drugs simultaneously. Multidrug resistance could mainly be attributed to the overexpression of the P-170 glycoprotein, considered as a drug-efflux pump encoded by the mdr 1 gene. Overexpression of this protein can be induced either by an accidental amplification or activation or both of the mdr 1 gene. Recent investigations focused on these mechanisms, aiming at a better understanding of the appearance of multidrug resistance during a chemotherapy. P-glycoprotein mediated drug resistance, however, is only one, albeit quite an important detoxification pathway, and some observations revealed genetic interactions with other systems. On the basis of this new knowledge, the development of novel therapeutic strategies to circumvent this clinical side-effect of cancer treatment has already begun.

Antineoplastic Agents↗
PubMed1991

Use of intravenous immunoglobulin in chronic lymphocytic leukemia. A brief review.

Chronic lymphocytic leukemia (CLL) is a disorder with multiple defects leading to an increased susceptibility to infection. Hypogammaglobulinemia is present in about 20% to 70% of patients with CLL. Intravenous immunoglobulin (IVIG) supplementation (400 mg/kg body weight every 3 weeks) prevented bacterial infections in these patients. An ongoing study is being conducted to compare doses of 250 mg/kg/mo with those of 500 mg/kg/mo in 36 patients included so far. As of this writing, the rate of infection in the two treatment groups was not significantly different, and no substantial loss of protection against bacterial infection was found in the lower-dose group. It seems likely that the lower dose is almost as effective as the standard therapy. If this is so, cost savings would be substantial.

Humans↗
PubMed1991

Treatment of advanced and refractory breast cancer with doxorubicin, vincristine and continuous infusion of verapamil. A phase I-II clinical trial.

Cancer cell resistance to several cytotoxic drugs, including doxorubicin and vincristine can be reduced in vitro by verapamil; this drug works at least in part by inhibitive competition for the multiple-drug resistance efflux-pump P-glycoprotein-170. To evaluate the clinical potential of this experimental concept we combined verapamil in continuous infusion with adriamycin and vincristine in the treatment of patients with advanced and anthracycline-refractory breast cancer. Sixteen patients were included and 55 treatment courses were given at different dose levels of chemotherapy; verapamil was given by continuous infusion of 0.003 mg kg-1 min-1 for 48 h. Overall, cardiac toxicity was low but a potentiation of neurotoxicity and hematotoxicity was observed. The objective response rate was 21% (3 partial responses in 16 patients) and the median survival was 6 months; these results are comparable to those of other second line treatment studies, using drugs not supposed to be cross-resistant.

Adult↗
PubMed1991

Prion diseases in man.

Human spongiform encephalopathies (HSE) are uncommon neurodegenerative diseases of unknown etiology. Whilst numerous observations provide arguments for an infectious disorder mediated by an unconventional agent of the so-called prion-type, the recent discovery of predisposing allelic variants suggests that HSE might be considered as genetically linked diseases.

Animals↗
PubMed1990

The regulation of gene expression and the molecular basis of cancer.

Over the last few years, the advent of new genetic techniques allowed a detailed analysis of the structural and functional organization of the genome and the genes in a living cell. After the discovery of cellular oncogenes, genes which are implicated in cell growth control and differentiation, recent investigations provided evidence to a crucial role played by certain gene regulatory DNA elements and oncoproteins in the molecular mechanisms of carcinogenesis.

Cell Transformation, Neoplastic↗
PubMed1990

Camembert, Listeria and the immunocompromised patient.

Listeriosis is a rare but well known infectious complication in pregnant women and immunocompromised patients. Epidemiological studies have shown an association between listeriosis and alimentary contamination by listeria of a variety of foodstuff including soft, ripened cheeses. We describe two case-reports of listeria meningitis with high evidence of food-related illness due to the consumption of contaminated camembert. These observations urged our State Department of Health to formulate a communication about alimentary listeriosis at the intent of all health care professionals, including recommendations for patients at risk.

Aged↗
PubMed1986

Acquired C1 esterase-inhibitor deficiency: case report with emphasis on complement and kallikrein activation during two patterns of clinical manifestations.

A case of severe angioedema with several episodes of life-threatening attacks during a follow-up of 7 years is presented. Although the biologic profile is that of an acquired C1 INH deficiency, no lymphoproliferative malignancy or immune-complex disease could be proven until now. However, the patient has had a small monoclonal IgG lambda-gammopathy for 4 years. During the last 4 years, edematous manifestations have stopped. The patient now suffers at regular intervals of about a week from short-lasting attacks with digestive and vasomotor symptoms. This clinical evolution is accompanied by a worsening in the complement abnormalities. The digestive and vasomotor attacks were found to be correlated with sudden prekallikrein and high-molecular-weight kininogen consumption. These findings demonstrate that prekallikrein is activated during acquired C1 INH deficiency and that the products of this pathway such as bradykinin are probably responsible for a part of the clinical manifestations associated with this disorder.

Aged↗
PubMed1986

Interleukin-2.

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Chemical Phenomena↗