Biomedical subjects

M G Paggi

Publications and source records attributed to M G Paggi.

58 records · Page 4Linked to original sources

PubMedDate not supplied

The membrane-bound hexokinase as a potential marker for malignancy in human gliomas.

Hexokinase is a key enzyme in carbohydrate metabolism. Its activity has been shown elevated in cells with high mitotic index. In particular, experimental cancer cells, due to their peculiar energy metabolism, display a hexokinase activity proportional to the degree of malignancy. This is the case also for human gliomas in which glucose metabolism, evaluated via positron emission tomography, has been shown to be predictive for patient prognosis. In order to better correlate these findings, specific reagents for tumor hexokinase (a polyclonal antibody and a full-length cDNA probe both specific for murine tumor hexokinase) have been successfully employed to quantitate the protein and its messenger in cultured cell lines; the antibody was also tested in four specimens obtained from human astrocytomas.

Astrocytoma↗

PubMedDate not supplied

Lonidamine in the combined treatment of malignant gliomas. A randomized study.

Lonidamine (LND) is a drug that interferes with energy metabolism of cancer cells, principally inhibiting aerobic glycolytic activity, by its effect on mitochondrially-bound hexokinase (HK). In such way LND could impair energy-requiring processes, as recovery from potentially lethal damage, induced by radiation treatment and by some cytotoxic drugs. A randomized study started in November 1983, to evaluate the efficacy of LND in association with radiotherapy as first line treatment in malignant gliomas, after surgical procedure. LND was also used in association with Lomustine (CCNU) at the moment of documented clinical and neuroradiological recurrence. At the present time 60 patients entered the study, and 47 are evaluable. Present preliminary results are not statistically significant, however indicate that LND tends to prolong the median survival time and the rate of one year survivors.

Adult↗

PubMedDate not supplied

Modulation of glycolysis in neuroepithelial tumors.

Among the features of the reprogrammed neoplastic phenotype there is the metabolic property to display an increased glycolytic capacity and the ability to convert glucose to lactic acid in the presence of oxygen. Human gliomas in vivo and in vitro are capable to metabolize glucose in a way strictly related to the pathological degree of malignancy. The drug Lonidamine [1-(2,4-dichlorobenzyl)-1H-indazol-3 carboxylic acid)] (LND) is able to selectively block hexokinase (HK) activity and, consequently, lactate production only in highly glycolytic (highly malignant) gliomas, stimulating, on the contrary, that of low grade gliomas; this basically depends on the different HK patterns between low and high grade gliomas. LND is under clinical trial in order to evaluate its effectiveness in glioma therapy.

Antineoplastic Agents↗

PubMedDate not supplied

Lonidamine-induced outer membrane permeability and susceptibility of mitochondria to inhibition by adriamycin.

Low concentrations of Adriamycin (ADM) do not inhibit the oxygen consumption of rat liver mitochondria because of the inability to cross the outer membrane. The involvement of this membrane as a permeability barrier is demonstrated by the results with exogenous ferrocytochrome c. ADM does not affect the basal rate of ferrocytochrome c oxidation, which, on the contrary, increases in Lonidamine (LND)-treated mitochondria. This difference lies in the capacity of LND to unmask the redox carriers in the inner membrane, i.e. cytochrome c:oxygen oxidoreductase which is also a marker of the outer membrane permeabilization. Therefore, the enhancement of ADM's effect on mitochondrial respiration by LND must be ascribed to its permeabilizing effect on the outer mitochondrial membrane.

Animals↗