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Biomedical subjects

P Marchetti

Publications and source records attributed to P Marchetti.

At least 289 records · Page 16Linked to original sources
PubMedDate not supplied

[Are mitochondria targets of anticancer drugs responsible for apoptosis?].

The vast majority of both chemical and physical anticancer treatments act through the induction of apoptotic cell death in vitro and in vivo. In numerous experimental systems, the apoptotic processes can be divided into three different phases. In the first one, multiple pro-apoptotic signal transduction pathways (e.g. P53, ROS production, etc.) are activated by various factors including anti cancer drugs. This first step is followed by an intermediate phase in which pro-apoptotic signals converge to mitochondria which in turn can finally trigger the last degradation phase of apoptosis. Consequently, mitochondria, play a pivotal role in the executive phase of apoptosis and could represent a novel attractive target for pro-apoptotic drugs. Indeed, unlike conventional anti tumour drugs which trigger pro-apoptotic signal transduction pathways upstream mitochondria, several compounds were shown to act directly on mitochondria to induce apoptosis. These drugs include betulinic acid, lonidamine, arsenic trioxide and two retinoids like CD437/AHPN and fenretinide/4-HPR. This review summarizes new data concerning these drugs targetted to mitochondria and highlights the new perspective they may offer in cancer therapy.

Animals↗
PubMedDate not supplied

[Can analysis of the molecular status of the p53 gene contribute to improving the therapeutic strategy for breast carcinoma?].

The occurrence of mutations in the p53 tumor suppressor gene is a specific and recurring genetic event in solid tumors. P53 plays a pivotal role in multiple cellular processes such as cell growth control, DNA repair and programmed cell death. Genotoxic damage, also induced by chemotherapy or radiotherapy, induces p53 overexpression in order to control the rate of proliferating damaged cells, thus triggering the mismatch repair or apoptotic pathways. P53 inactivation determines a condition of genetic instability, justifying the subsequent susceptibility to acquire mutations of different other genes. P53 mutations are associated with worse prognosis and with chemo/radioresistance, due to the inability to trigger p53-dependent programmed cell death. Molecular diagnostic strategies show 32% p53 mutations in breast cancer. The analysis of the p53 gene performed by FAMA (Fluorescence Assisted Mismatch Analysis) in high-risk breast cancer patients with > or = 10 involved axillary nodes may help identify a subset of very high risk BC patients (vHR-BC) with poorer prognosis and a subset with better prognosis, potentially responsive to medical treatments. The accurate evaluation of the p53 status can predict prognosis and sensitivity to chemotherapy, thus representing the first step toward better definition of therapeutic strategies according to the molecular characterization of the individual patient.

Apoptosis↗
PubMedDate not supplied

[Micro-array based technologies to study the proteome: technological progress and applications].

Since these twenty last years, there is an increasing interest for large-scale analysis of biological function. In the field of transcriptome, the emergence of microarray-based technologies and the design of DNA biochips allow high-throughput studies of RNA expression in cell and tissue at a given moment. In the field of proteome, methods of reference are still the 2D electrophoresis followed by analysis with mass spectrometry. Technological progress makes it possible to apply microarray methods to proteomics study : they are protein biochips or protein arrays. Expression analysis of proteins in a cell or a tissue in simultaneous and highly parallel way give further information for large-scale studies of signaling pathway. Numerous applications of protein microarray-based assays are described in basic biological research and in medical research to identify diagnostic biomarkers of inflammatory and cancerous pathologies and to find out news drugs and new therapeutic targets. This review summarizes concrete applications of microarray-based technology in the field of proteome, describes fundamental technical stages in protein array development and highlights critical points which will be useful to improve this emerging proteomic method.

Protein Array Analysis↗
PubMedDate not supplied

Do metformin and phenformin potentiate differently B-cell response to high glucose? An in vitro study on isolated rat pancreas.

The study investigated the effects of metformin and phenformin, at "therapeutic" concentrations, on the pancreatic A-, B- and D- cell response to glucose using the isolated perfused rat pancreas model. Changes in the rate of pancreatic lactate output after these biguanides were also evaluated. Metformin--at 1.5 micrograms/ml--and phenformin--at 100 ng/ml--were separately infused both at 160 mg/dl and 300 mg/dl glucose levels. Neither metformin nor phenformin affected glucagon or somatostatin secretion during these two metabolic stimuli with glucose, nor did they significantly influence insulin response to the lower glucose stimulus. Both metformin and phenformin enhanced insulin response to 300 mg/dl glucose infusion and increased the second phase of the B-cell secretory profile but only phenformin significantly enhanced the pancreatic lactate output rate during the 300 mg/dl glucose infusion. Infusion with dichloroacetate (a stimulator of the mitochondrial pyruvate oxidation) or with verapamil (a calcium antagonist) alone did not modify the insulin response to high glucose concentrations. During metformin infusion dichloroacetate neither modified metformin's effects on B-cell response to high glucose nor did it affect the pancreatic lactate output rate. On the other hand dichloroacetate opposed phenformin's effects on the B-cell response to high glucose and reversed the rise in the pancreatic lactate output rate. Verapamil inhibited the effect of metformin on the B-cell response to high glucose but failed to affect phenformin's influence on high-glucose induced insulin release. These data suggest both metformin and phenformin potentiate--at least in rats--the late phase of insulin secretory response to high glucose. However metformin seems to influence pancreatic B-cell activity mainly by facilitating the trans-membrane calcium ion influx responsible for the second phase of insulin release. Phenformin's influence seems indirect since it increases pancreatic lactate production which mediates the enhanced B-cell response to glucose.

Animals↗
PubMedDate not supplied

Antitumor effect of lonidamine alone or combined with tamoxifen or medroxyprogesterone acetate in breast cancer cells.

The effect of Lonidamine (LND) alone or combined with the antiestrogen Tamoxifen (TAM) or Medroxyprogesterone acetate (MPA) on cell proliferation and steroid hormone receptor content of a human estrogen sensitive breast cancer cell line was investigated. LND has a direct growth inhibitory action, even if used at relatively low concentrations (10(-7) M), and shows the maximum effect at 10(-4) M. The combination of LND with the antiestrogen does not produce a potentiation of the TAM-induced reduction of cell number, while the association of the drug with MPA seems more effective with respect to MPA alone, at least at certain concentrations. The negative interference observed between LND and TAM may be due to the LND-induced decrease of estrogen receptor levels.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Antiproliferative effect of lonidamine on a human glioblastoma multiforme cell line.

Recent data from phase II trials have shown that lonidamine (LND) is effective in the treatment of tumors of various histogenesis, including gliomas. In the present work, we tested the antiproliferative effect of LND on a human glioblastoma cell line (LI) in different culture conditions. When LI are cultured in their standard conditions, a reduction of cell growth is seen after 3 days of treatment with 10(-4) M LND. It reaches 70% with respect to control after 6 days and is statistically significant. LND is ineffective at the other concentrations tested. In more stringent culture conditions, 10(-4) M LND determines a higher inhibition of cell proliferation both after 3 and 6 days of exposure, while other doses of LND are unable to affect cell growth.

Antineoplastic Agents↗
PubMedDate not supplied

Salivary immunoreactive insulin concentrations are related to plasma free-insulin levels in insulin-treated diabetic patients.

Salivary immunoreactive insulin was measured in 45 insulin-treated diabetic patients directly from saliva samples by a radioimmunoassay procedure. Mean and median fasting salivary immunoreactive insulin was respectively 88.5 and 54.0 pmol/L (range 12.2-633.6 pmol/L); fasting salivary insulin values were positively correlated with steady-state plasma free-insulin levels measured in immediately extracted plasma samples (r = 0.62, p less than 0.001) and with daily insulin dose (r = 0.32, p less than 0.05). After subcutaneous injection of 15 U regular insulin in 6 type 1 diabetic patients, salivary insulin concentrations increase reflected that of plasma free-insulin during a 6 h period although with a 60 min time lag. Mean salivary insulin values and plasma free-insulin concentrations were significantly correlated to each other both at each time point (p less than 0.001) and when the mean salivary insulin levels were plotted against the mean plasma free-insulin values 60 min earlier (p less than 0.001). These results suggest that the measurement of salivary immunoreactive insulin (that is easier, faster and cheaper than plasma free-insulin assay) may be usefully employed as an approximation of plasma free-insulin concentrations for clinical and research purposes in patients with circulating anti-insulin antibodies.

Adult↗
PubMedDate not supplied

[Influenza vaccination and polyradiculoneuritis of the Guillain-Barré type].

The Authors present a Guillain-Barré like case of polyradiculoneuritis occurring two weeks after the 1988-89 influenza vaccination. The existence of similar cases recently reported in the literature and their frequent association with swine influenza vaccination suggest the opportunity of a better epidemiological survey of similar cases.

Aged↗
PubMedDate not supplied

Metformin potentiates B-cell response to high glucose: an in vitro study on isolated perfused pancreas from normal rats.

This study investigated the effects of metformin on pancreatic A-B- and D-cell functions using the isolated perfused rat pancreas model. The lactate output rate following metformin infusion was also monitored. Metformin was infused at the low "therapeutic" concentration of 1.5 micrograms/ml and its effects were evaluated in three different glycaemic conditions: during a basal infusion of 4.44 mM glucose, during a moderate increase to 8.88 mM of glucose concentration, and finally during a higher 16.66 mM glycaemic stimulus. Basal insulin secretion and B-cell release during the lower hyperglycaemic stimulus were unaffected by metformin infusion. On the contrary, the drug significantly enhanced insulin response to 16.66 mM glucose, particularly by increasing the second phase of hormone release. Glucagon and somatostatin releases during metformin infusion were similar to the secretory pattern observed in the control experiments both in the basal condition and in the presence of the two different hyperglycaemic stimuli. Finally metformin did not modify the lactate output rate from perfused pancreas, irrespective of the different glycaemic conditions employed. Therefore our data suggest--at least in rats, in in vitro experiments but above all in the presence of markedly elevated hyperglycaemic conditions--that metformin may influence the glucose stimulatory effect on B-cell activity.

Animals↗