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Biomedical subjects

E Villa

Publications and source records attributed to E Villa.

At least 109 records · Page 6Linked to original sources
PubMed1994

Modulation of drug-induced cytotoxicity by a bispecific monoclonal antibody that recognizes the epidermal growth factor receptor and doxorubicin.

A hybrid hybridoma secreting a bispecific hybrid mAb (bsmAb), which recognizes both the epidermal growth factor receptor (EGF-R) and the drug doxorubicin, was produced by somatic hybridization of two hybridomas. The bsmAb obtained was able to retarget doxorubicin cytotoxicity in vitro specifically on EGF-R-positive cells exerting at the same time an antidotal effect on cells that did not overexpress the EGF-R. Distribution studies in mice indicate that the bsmAb selectively delivers the drug to tumour cells and modifies doxorubicin biodistribution with a statistically significant decrease of drug concentration in the intestine, which is the main target of early anthracycline toxicity. In keeping with this finding is the remarkable antidotal activity exerted by bsmAb in mice treated with doxorubicin, which is proved by retardation in loss of body weight and mortality. The effectiveness on tumour growth of the mAb followed by the administration of doxorubicin appears to be equal to that of the drug alone; however, the bsmAb exerts a remarkable antidotal activity.

Animals↗
PubMed1994

Surgery following neoadjuvant MPV chemotherapy (mitomycin, cisplatin, vinblastine) in locally advanced (IIIa and IIIb) non-small cell lung cancer.

From November 1990 to August 1993, 32 patients with non-small cell lung cancer (NSCLC) entered a multimodality treatment study with neoadjuvant Mitomycin, Cisplatin and Vinblastine (MPV), surgery and radiotherapy at the San Raffaele Hospital in Milan, Italy. Neoadjuvant chemotherapy was performed on an outpatient basis. To date 23 patients (11 stage IIIa and 12 stage IIIb) have completed the chemotherapy treatment and are available for evaluation of response, toxicity, surgical eligibility and resection rate. The overall major response to MPV chemotherapy was 87%. The overall resection rate after major response to treatment was 60% (90% in stage IIIa and 17% in stage IIIb). After a median follow-up of 21 months (8-31) 17 patients are still alive (74%). Ten patients (83%) who had a complete resection are alive after a median follow-up of 23 months (21-30) and eight of them (66%) are in complete pathological remission. No treatment-related mortality was observed. The authors conclude that MPV is a highly effective neoadjuvant regimen for NSCLC and is feasible on an outpatient basis. Favorable resection rates can be obtained in stage IIIa patients. Stage IIIb patients can be downstaged and undergo complete resection. A longer follow-up is needed to assess the impact of this multimodality approach on long-term survival and to evaluate the role of adjuvant radiotherapy.

Adult↗
PubMed1994

Relevance of antibody valency in EGF receptor modulation.

Binding characteristics of a monovalent bispecific monoclonal antibody (bsMoAb), which recognizes both epidermal growth factor receptor (EGF-R) and drug doxorubicin (DXR) were compared with those of the parental bivalent MoAb directed against the EGF-R binding site. Scatchard analysis indicated that both MoAbs bound to EGF-R-overexpressing A431 cells with the same affinity. In tracer amounts, both MoAbs also displayed the same capacity to be internalized after binding to the cell surface. However, when the MoAbs were used at saturating concentrations, down-modulation of the receptor was greater with the bivalent MoAb. The bivalent MoAb also inhibited proliferation of A431 cells both in vitro and in vivo whereas the bsMoAb was inhibitory only in vivo. These data suggest that MoAb bivalency is required for EGF-R down-modulation and in vitro cell growth inhibition.

Animals↗
PubMed1993

Effects of captopril on sympathetic activity, lipid and carbohydrate metabolism in a model of obesity-induced hypertension in dogs.

Ten age-matched beagle dogs were kept on a high-fat diet and followed for 12 weeks. During this period the animals were divided into two groups (n = 5), either with or without oral captopril treatment. Dogs were tested periodically for biochemical and clinical parameters, and at the end of the study animals were killed and thoracic aorta samples were obtained for histologic evaluation. From the third week, the captopril group presented significantly lower values of mean arterial pressure, plasma norepinephrine, and fasting glucose and cholesterol levels than those attained in the nontreated group. Furthermore, aorta samples from untreated animals showed profuse staining for fat content at the intima and adventitia layers, while this reaction was restricted to the outer layer in treated dogs. These data suggest that the beneficial effects of captopril therapy in this obesity-induced hypertension model could be based on blood pressure control, together with reduction of serum glucose, cholesterol, and sympathetic activity levels. In addition, captopril treatment could play a role in the retardation of the early stages of vascular atherogenetic lesion.

Animals↗
PubMed1993

Cicaprost, a prostacyclin analog, protects renal function in uninephrectomized dogs in the absence of changes in blood pressure.

Ten dogs presenting mild chronic renal failure and hypertension after 27 months of uninephrectomy, during which they received a high sodium and high protein diet, were divided in two groups (n = 5) and followed for 15 months. The same diet was maintained and one of the groups received cicaprost treatment. The animals were periodically tested for biochemical and clinical parameters, and at months 0, 3, 6, and 15, glomerular filtration rate and renal plasma flow (RPF) were measured. Renal biopsies were made after 6 months of follow-up. Control group showed a higher thickening of pre- and intraglomerular portions of arteriolar vessels and an enhancement of mesangial matrix when compared with the treated group. Cicaprost also induced a significant elevation in RPF and a significant decrease in filtration fraction. All these findings suggest that cicaprost, an oral stable prostaglandin I2 analog, could have a protective renal effect in this experimental model.

Animals↗
PubMed1993

Properties of the purified hypothalamic pituitary NA/K-ATPase inhibitor.

Previously we described the isolation and final purification of an endogenous sodium-pump inhibitor from the CNS, mainly from bovine hypothalamus and pituitary. The purification protocol consisted of lipophilic chromatography, followed by lipid extraction, and semipreparative and analytical reverse-phase high-pressure liquid chromatography. The bioassays used were in vitro Na+/K(+)-ATPase inhibition, and 3H-ouabain displacement from its specific binding site in the enzyme structure, as well as inhibition of 86Rb uptake from human red blood cells. We have obtained, from both tissues, a low-molecular-weight, nonpeptidic, nonlipidic substance that elutes as a single peak highly pure according to criteria of coincidence of its spectra properties. When rechromatographed in two different chromatographic systems, the same homogeneous peak is obtained suggesting complete purity. This pure substance can be isolated from other bovine tissues as well as from human plasma and human placenta. It shows a very distinctive fluorescence spectrum and it behaves as a potent inhibitor of the Ca2+ pump of synaptosomal plasma membrane.

Animals↗
PubMed1993

Natriuretic effects of dopamine agonist drugs in models of reduced renal mass.

In addition to recognized neurotransmitter properties in the central nervous system, dopamine (DA) plays a role in the physiological activity of the kidney through its hemodynamic and natriuretic effects. On the basis of these data, some pharmacological interventions have focused their attention on the use of DA-related drugs to improve renal sodium handling. We summarize the data obtained from two studies using two DA agonist drugs, lisuride (LIS) and fenoldopam (FEN), in two situations of reduced renal mass. During an intravenous sodium load performed on 10 uninephrectomized dogs, LIS induced a significant blockade of the concomitant pressor response, estimated by lower blood pressure and norepinephrine levels. Under these same conditions, FEN significantly decreased blood pressure and elevated the natriuretic response. In a second study, when FEN was administered at nonhypotensive doses to chronic renal failure patients, it evoked an enhancement of diuresis, natriuresis, and creatinine clearance. These data seem to confirm the involvement of DA in the regulation of cardiovascular homeostasis and its role in renal sodium handling. Furthermore, these beneficial effects support the use of DA-related drugs in the field of hypertension.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Influence of calcium intake on calcitriol levels in idiopathic hypercalciuria in children.

Twenty-four children with idiopathic absorptive hypercalciuria (IAH) and a control group (CG) of 11 healthy children were studied. Plasma 1,25-hydroxyvitamin D3 (calcitriol), parathyroid hormone (PTH), calcium (Ca) and phosphate (P) levels were measured during dietary manipulation. The three diets analyzed were: (A) calcium-restrictive diet (400 mg/1.73 m2/day) for 7 days; (B) supplemented diet (1,000 mg/1.73 m2/day) for 3 days; (C) supplemented diet continued for 15 days. The IAH group had higher levels of serum calcitriol than the control group for all three diets. Serum calcitriol levels in the IAH group decreased in diet B compared to diet A, and returned to levels observed with diet A during diet C. Serum Ca, P and plasma PTH levels did not vary throughout the study in either group. In IAH, two subgroups were observed. In one, serum calcitriol levels were elevated and in the other, serum calcitriol levels were not different from the controls. This second group had a lower P and maximum rate of tubular reabsorption of phosphate per 100 ml of glomerular filtrate than the IAH group with elevated serum calcitriol levels and the control group. These results suggest that IAH in children may be related both to increased serum calcitriol levels and to an altered Tmp/GFR.

Adolescent↗
PubMed1993

Diagnosis of insulin resistance.

Soon after the discovery of insulin, the importance of insulin sensitivity assessment was recognised. Recently, the role of insulin resistance in cardiovascular morbidity and mortality has been widely accepted and many methods for in vivo assessment of insulin resistance have been developed. They may be classified as 'closed-loop' techniques (in which insulin and glucose concentrations are allowed to interact freely), 'open-loop' techniques (in which insulin and/or glucose levels are fixed) and 'model methods' (which use a mathematical model to analyse the interactions between insulin secretion patterns and glucose disposal). Although there is no ideal method available to date, open-loop techniques avoid many of the difficulties involved in the interpretation of closed-loop or model methods, and are preferred by most investigators. The glucose clamp technique is recognised as the 'gold standard' for assessment of insulin sensitivity; however, the insulin suppression test is adequate in most circumstances and is much simpler to perform.

Animals↗
PubMed1993

Salvage treatment after r-interferon alpha-2a in advanced neuroendocrine tumors.

The use of inteferon (IFN) in neuroendocrine advanced tumors has achieved control of hormonal symptoms but low objective tumor response rate. In patients resistant to, or failing on, IFN a second line treatment may be required. Seventeen patients having received recombinant IFN alpha-2a as last treatment entered the study. There were 12 carcinoids, 3 medullary thyroid carcinomas, one Merkel cell carcinoma, and one neuroendocrine pancreatic tumor. Two different treatments were used: one radiometabolic therapy with metaiodobenzylguanidine (MIBG) in 3 patients with high MIGB uptake and one polychemotherapy regimen, including streptozotocin 500 mg/m2 intravenously days 1, 2, 3 and epirubicin 75 mg/m2 intravenously day 1, in the remaining 14 patients. Stable disease with relief of symptoms and tumor marker reduction was obtained in two patients receiving MIGB therapy, whereas the third patient had progressive disease. In the chemotherapy group only one partial response was obtained and neither tumor marker reduction nor subjective improvement were seen. Our second-line treatment was not especially effective but may be considered for rapidly progressive and/or symptomatic disease. The radiometabolic therapy appears promising in symptomatic patients with small tumor burden whereas our chemotherapy regimen appears ineffective.

3-Iodobenzylguanidine↗
PubMed1992

An anti-doxorubicin monoclonal antibody modulates kinetic and dynamic characteristics of the drug.

A monoclonal antibody (MAb) directed against doxorubicin (DXR), denominated MAD II, was found to exert an antidotal action by modulating the kinetic and dynamic characteristics of the drug. In vitro, MAD II has been found to reduce the cytotoxicity of DXR and the drug uptake on spleen lymphocytes more efficiently than on tumor cells (P388 leukemia cells). In vivo, the anti-DXR MAb modified the drug distribution; the drug uptake was found to be reduced in the intestine and myocardial tissues and increased in the tumor, liver and spleen. In mice treated with DXR, the administration of anti-DXR MAb exerted an antidotal activity which was proved by the reduction in body-weight loss and mortality. In contrast, the therapeutic efficacy of the drug in P388-tumor-bearing mice was not influenced by the anti-DXR MAb.

Animals↗
PubMed1992

Immunogenicity and safety of a recombinant hepatitis B vaccine produced in mammalian cells and containing the S and the preS2.

A group of 273 health care workers, at risk of HBV infection, underwent vaccination with recombinant HBsAg produced in mammalian cells and containing protein sequences coded by both the S and pre-S2 regions (Genhevac B). Preliminary results show that a very early pre-S2 response occurred which may be useful in post-exposure prophylaxis. This observation, in addition to reduced influence by the vaccination protocol, provides grounds for optimism in spite of the fact that the efficiency spectrum of this vaccine was not superior to that of recombinant vaccines produced in yeast.

Adolescent↗