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Biomedical subjects

P Pani

Publications and source records attributed to P Pani.

At least 55 records · Page 3Linked to original sources
PubMed1991

Lonidamine in non-small-cell lung cancer: a phase II study.

The activity of lonidamine (a derivative of indazole-carboxylic acid and a new drug with a characteristic antitumor activity) was evaluated in non-small-cell lung cancer (NSCLC). Twenty-five patients with NSCLC with or without prior treatment received lonidamine at the dose of 450 mg/daily p.o. up to progression. Objective responses obtained were: 3 (12%) partial responses and 3 (12%) minor responses with a mean duration of 13.7 weeks for partial responses. Mean duration of treatment was 20 weeks (range 4-97+). During to the drug's characteristics, bone marrow toxicity was not observed; myalgia and mild testicular pain were the most significant side effects.

Adult↗
PubMed1991

Chronic mitoinhibition during promotion of hepatocarcinogenesis.

We have reported previously that orotic acid (OA), a precursor for pyrimidine nucleotide biosynthesis, is able to promote carcinogenic process in both liver and duodenum of rats. The present study investigates the possible role of mitoinhibitory effects of OA as being responsible for its promotional effects. Male Fischer 344 rats were given a semisynthetic basal diet (BD) or a diet containing 1% OA for four weeks coupled with 2/3 partial hepatectomy (PH), and all animals were then continued on BD for an additional four weeks. This protocol is known to exert a promoting effect on the initiated rat liver. Livers were perfused, and the labeling index (LI) of isolated cultured hepatocytes was monitored. Hepatocytes isolated from livers of rats fed a BD or 1% OA exhibited in vitro an LI of 39 +/- 2 and 24 +/- 1%, respectively. The lowered in vitro LI was seen even upon exposure to epidermal growth factor (EGF) (67 +/- 2% in OA-treated livers compared to 91 +/- 2% in hepatocytes from control rat liver). A similar four-week exposure to OA coupled with PH decreased hepatic DNA synthesis induced by a choline-deficient diet in vivo by about 50%. These results indicate that OA is able to decrease the response of normal hepatocytes to growth factors and suggest a possible mechanism of chronic differential mitoinhibition as a basis for promotion induced by OA.

Animals↗
PubMed1991

Total and HDL cholesterol in human hematologic neoplasms.

In this study serum cholesterol was measured in different types of human hematologic malignancies characterized by a wide range of cell proliferation. In all tumoral types a significant decrease of HDL cholesterol was observed, whereas total serum cholesterol generally remained unchanged. Another interesting observation of our study was the apparent inverse correlation between the extent of cell proliferation in these neoplastic disorders and the level of HDL cholesterol. Since a decrease of HDL cholesterol was previously observed, in our laboratory, in different experimental models of normal and neoplastic cell proliferation, we suggest that the decrease of HDL cholesterol may be a generalized phenomenon related to massive cellular growth in normal and malignant processes.

Adult↗
PubMed1990

Glucose-6-phosphate dehydrogenase (G6PD) activity in tumoral tissues of G6PD-deficient subjects affected by larynx carcinoma.

The activity of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the hexose monophosphate (HMP) shunt pathway, was measured in both normal and tumoral larynx tissues from normal and G6PD deficient subjects. Significant increases of this enzymatic activity were found in tumoral tissues of both normal and G6PD deficient subjects, who were characterized by very low levels of G6PD activity in erythrocytes as well as in larynx tissue.

Aged↗
PubMed1990

Cell proliferation and promotion of rat liver carcinogenesis: different effect of hepatic regeneration and mitogen induced hyperplasia on the development of enzyme-altered foci.

A series of experiments was performed to investigate the effect of different types of cell proliferation on the development of enzyme-altered preneoplastic hepatic foci in male Wistar rats. Animals were given a single dose of diethylnitrosamine (100 mg/kg body weight). After a 2-week recovery period liver cell proliferation was repeatedly induced by four or eight necrogenic doses of carbon tetrachloride (compensatory cell proliferation), or by four or eight treatments with three different liver mitogens, namely lead nitrate, ethylene dibromide and nafenopin (direct hyperplasia). The carcinogen altered hepatocytes were monitored as gamma-glutamyltransferase positive or adenosine triphosphatase negative foci. The results indicate that compensatory cell proliferation induced by both four and eight carbon tetrachloride treatments enhanced the growth of diethylnitrosamine-initiated hepatocytes to enzyme-altered foci. On the contrary, repeated waves of cell proliferation induced by liver mitogens did not result in any significant number of enzyme-altered foci.

Adenosine Triphosphatases↗
PubMed1990

Serum lipoproteins during bone marrow hyperplasia after phenylhydrazine administration in rats.

In the present study, lipoprotein metabolism was investigated during compensatory hyperplasia of bone marrow after haemolysis induced by phenylhydrazine (20 mg/kg b.w.) administration in rats. The rats were sacrificed at different time intervals (0, 1, 2 and 5 days) after phenylhydrazine treatment. Analysis of the different fractions of lipoproteins has shown that during bone marrow hyperplasia there is an alteration of lipoprotein profiles, mainly due to a decrease of HDL2 and HDL3 subfractions.

Animals↗
PubMed1990

Multiple molecular forms of rat liver glucose-6-phosphate dehydrogenase during liver hyperplasia induced by lead nitrate.

In the present study the three dimeric molecular forms of rat liver glucose-6-phosphate dehydrogenase were investigated during liver hyperplasia induced by lead nitrate. An increase of band 3 and a concomitant decrease of band 1 was found, indicating that this proliferating process is characterized by a peculiar pattern in the distribution of liver G6PD activity. Since the same pattern was observed also in liver hyperplasia induced in fasted animals, a condition otherwise characterized by a shift towards band 1, we suggest that during proliferating processes the metabolic control normally exerted by fasting on the enzymatic activity is overcome.

Animals↗
PubMed1990

Modifying influence of fasting on liver hyperplasia induced by lead nitrate.

Previous studies by our laboratory have shown that lead nitrate when injected intravenously as a single dose to rats, induces a hyperplastic response in the liver. Liver hyperplasia was accompanied by an increase in cholesterol synthesis, an accumulation of cholesterol esters and by a stimulation of hexose-monophosphate (HMP) shunt enzyme activities. In the present report, hepatic DNA, mitotic index, cholesterol metabolism, as well as glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) activities, were investigated during liver hyperplasia induced by lead in fasted rats. Fasting was chosen as an experimental model characterized by a very strong depression of those metabolic pathways (cholesterol synthesis and HMP shunt) that we have found related to liver hyperplasia. The mitogenic response, even if at minor extent, also occurs in liver of fasted rats. A stimulation of cholesterol synthesis and HMP shunt enzyme activities, was also observed in lead-treated fasted rats, adding further support to the fact that an endogenous source of newly synthesized cholesterol together with a suitable increase of HMP shunt enzyme activities is needed during hepatic cell proliferation.

Animals↗
PubMed1989

Variations of serum lipoproteins during cell proliferation induced by lead nitrate.

In the present study serum lipoproteins were investigated during cell proliferation induced by a potent mitogen, lead nitrate. A strong decrease in HDL2 and a concomitant increase in HDL3 were observed in lead-treated rats. The recovery of normal lipoprotein pattern took place together with the regression of hyperplastic process. Since a decrease in HDL also occurs under other conditions of cell growth, we hypothesize that a decrease in HDL, mainly in HDL2 subfraction, may represent a generalized phenomenon related to massive cell proliferation.

Animals↗
PubMed1989

Further evidence that mitogen-induced cell proliferation does not support the formation of enzyme-altered islands in rat liver by carcinogens.

Our earlier studies have revealed that direct hyperplasia induced by liver mitogens such as lead nitrate, ethylene dibromide, nafenopin and cyproterone acetate, unlike compensatory cell proliferation induced by partial hepatectomy and CCl4, does not support the formation of enzyme-altered islands induced by chemical carcinogens in the liver. In the previous studies carcinogens were given at the peak of DNA synthesis induced by the liver mitogens. If the mitogens have altered the sensitive phase of the hepatocyte to the carcinogenic attack, administering the carcinogen at one time point following the mitogenic stimulus might have missed the sensitive phase. In order to overcome this possibility in the present study male Wistar rats weighing 200-250 g were given N-methyl-N-nitrosourea (MNU; 60 mg/kg, i.p.) at three points representing G1, S and G2/M phases of the cell cycle following different types of liver cell proliferative stimuli. In another experiment MNU (60 mg/kg, i.p.) and diethylnitrosamine (15 mg/kg, i.p.) were given prior to the administration of proliferative stimuli. The initiated hepatocytes were also assayed following promotion by two different promoting regimens, namely phenobarbital and the resistant-hepatocyte model. Further, the initiated hepatocytes were monitored not only by using the appearance of islands of enzyme-altered hepatocytes but also using the incidence of hepatocellular carcinoma. The results of this study clearly revealed that irrespective of the protocol used, only the compensatory liver cell proliferation but not the mitogen-induced direct hyperplasia supported the formation and the growth of enzyme-altered islands in the liver induced by chemical carcinogens.

Adenosine Triphosphatases↗
PubMed1989

Cell deletion by apoptosis during regression of renal hyperplasia.

Regression of renal hyperplasia after withdrawal of the mitogenic stimulus induced by a single injection of lead nitrate was studied in male Wistar rats. Lead nitrate administration (10 mumol/100 g body weight) resulted in a ninefold increase in the incorporation of labeled thymidine into renal DNA and in an enhancement in the mitotic index; these changes were accompanied by an increase in the organ weight and DNA content that reached a maximum at 2 days. Regression of the renal hyperplasia was observed as early as 3 days after treatment and was completed within 2 weeks. Although lytic necrosis was not responsible for cell loss, the elimination of the excess renal cells took the form of apoptosis. This distinctive mode of cell death, which has been implicated in the involution of hyperplasia in other tissues and organs, was characterized by the occurrence of intracellular and extracellular membrane-bounded eosinophilic globules that often contained nuclear fragments. It affected mainly cells of the proximal tubules, and it was not detected once the kidney had regressed to its original mass. These results support the hypothesis that apoptosis is involved in the regulation of organ size.

Animals↗
PubMed1988

Relationship between DNA and cholesterol synthesis in kidney after refeeding.

DNA and cholesterol synthesis were investigated in the kidneys of fasted-refed rats. Refeeding resulted in an increase in kidney DNA synthesis, as measured by 3H-thymidine incorporation, starting at 72 h. The increase in DNA synthesis was accompanied by a stimulation of cholesterol synthesis, as measured by 14C-acetate incorporation into cholesterol.

Animals↗
PubMed1988

Hexose monophosphate shunt enzymes in lung tumors from normal and glucose-6-phosphate-dehydrogenase-deficient subjects.

Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate, dehydrogenase the key enzymes of the hexose monophosphate shunt pathway, were measured in both surrounding and tumoral lung tissues from normal and G6PD-deficient subjects. A significant increase of these enzymatic activities in tumoral tissue was found not only in G6PD-normal patients, but also in G6PD-deficient patients with very low or nonmeasurable G6PD activity in both erythrocytes and normal lung tissue.

Adult↗
PubMed1988

Comparative effects of insulin and refeeding on DNA synthesis, HMP shunt and cholesterogenesis in diabetic and fasted rats.

DNA synthesis, cholesterogenesis and the enzymes of the hexosemonophosphate (HMP) shunt pathway were investigated in liver of diabetic rats treated with insulin and in fasted/re-fed rats. Both insulin and refeeding were found to induce liver cell proliferation, accompanied by a remarkable increase in cholesterogenesis. An enhancement of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (G6PD) activities was also found in insulin-treated diabetic rats and in re-fed rats, supporting the concept that these two enzymes are involved in the proliferative process. Since insulin did not exert the same biochemical effects in a non replicating cell population, such as in insulin-treated normal rats, these studies provide new evidence of a close correlation between DNA, cholesterol synthesis and HMP shunt enzymes during cell proliferation.

Animals↗
PubMed1988

Modulation of the activity of hepatic gamma-glutamyl transpeptidase, adenosine triphosphatase, placental glutathione S-transferase and adenylate cyclase by acute administration of lead nitrate.

The effect of a single administration of lead nitrate on the activity of gamma-glutamyltranspeptidase (gamma-GT), adenosine triphosphatase (ATPase), the placental form of glutathione S-transferase (GST-P) and adenylate cyclase (AC), four enzymes widely used as phenotypic markers for preneoplasia, was investigated in the liver of male Wistar rats. The results of the histochemical enzymatic staining indicated that an acute treatment with lead nitrate induces the activity of gamma-GT, mainly in the hepatocytes located around zone I of the liver acinus, with a maximum seen between 72-96 hours. On the other hand, the activity of ATPase was found to be severely inhibited at 2-3 days after treatment, as shown by a strong decrease in the staining of the bile canaliculi of zones II and III. Immunohistochemical analysis revealed that lead nitrate administration also resulted in the appearance in most of the hepatocytes of GST-P, an enzyme whose activity is almost undetectable in normal rat liver, but is elevated in preneoplastic liver lesions. Finally, lead nitrate treatment resulted in an inhibition of AC activity which was maximal after 24 hours.

Adenosine Triphosphatases↗
PubMed1987

Hexose monophosphate shunt and cholesterogenesis in lead-induced kidney hyperplasia.

De novo cholesterol synthesis and hexose monophosphate (HMP) shunt were studied in rat kidney stimulated to proliferate by a single administration of lead nitrate. Lead-treated rat kidneys showed an increase in DNA synthesis, as measured by [3H]thymidine incorporation starting at 18 h and with a maximum at 24 h. Renal DNA synthesis was preceded by an increase in de novo cholesterol synthesis and an enhancement in the activity of the HMP shunt, as indicated by increased activity of G6PDH and 6PGDH. These findings indicate that enhancement of cholesterol synthesis and of the HMP shunt is closely associated with the active proliferative process induced in the kidney by treatment with lead nitrate.

Animals↗
PubMed1987

Liver cell proliferation induced by the mitogen ethylene dibromide, unlike compensatory cell proliferation, does not achieve initiation of rat liver carcinogenesis by diethylnitrosamine.

The purpose of this investigation was to determine whether mitogen-induced cell proliferation is as effective as compensatory cell proliferation in achieving initiation of carcinogenesis in rat liver. Male Wistar rats were injected with a single non-necrogenic dose of the hepatocarcinogen diethylnitrosamine (DENA) during the peak of DNA synthesis following the administration of the hepatic mitogen ethylene dibromide (EDB) or a necrogenic dose of CCl4. After subjecting the animals to a promoting procedure, the rats were sacrificed and the initiated hepatocytes were monitored as gamma-glutamyltranspeptidase (gamma-GT) positive foci. The results indicate that while DENA administration during compensatory cell proliferation results in the formation of GT positive foci, no enzyme-altered foci were produced when the carcinogen was given during liver hyperplasia induced by EDB, despite the fact that at the time of carcinogen administration, the extent of cell proliferation, as monitored by thymidine incorporation into DNA, was the same in both the groups.

Animals↗