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G Lima

Publications and source records attributed to G Lima.

33 records · Page 2Linked to original sources

Intrinsic and extrinsic factors in estrogen action in human breast cancer: role of polyamines and pituitary factors.

Although polyamines are important in regulating proliferation of mammalian cells, their role in hormone induction of cell growth has not been delineated. In the estradiol-responsive human breast cancer cell line, T-47D clone 11, estradiol (10(-10) M) was able to stimulate cell proliferation and the activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the biosynthesis of polyamines. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, blocked the estradiol-induced cell proliferation and ODC activity. Exogenous addition of putrescine, the natural product of ODC, rescued the inhibitory effect of DFMO. In addition, DFMO abolished the estradiol-induced growth of several other estrogen-responsive human breast cancer cell lines but did not affect the growth of hormone-independent cell lines. Further, a serum factor was found to be required for estradiol to exert its effect. To gain insight into the nature of this and possibly other extrinsic factors involved, the effect of estradiol on the proliferation of T-47D cells transplanted into athymic nude mouse was evaluated. In this in vivo system, estradiol alone produced only moderate growth of the human breast tumor. The simultaneous transplantation of a prolactin (PRL)- and growth hormone (GH)-secreting rat pituitary tumor or normal rat pituitary glands at a different site dramatically potentiated the effect of estradiol on the growth of the breast tumor xenograft. Purified PRL or GH were without effect, indicating that the active pituitary factor is neither PRL nor GH. Further, conditioned medium from rat pituitary tumor cells potentiated the mitogenic effect of estradiol on T-47D and several other estrogen receptor-positive human breast cancer cell lines in vitro under serum-free condition. In conclusion, we have identified both intrinsic (polyamines) and extrinsic (pituitary/serum) factors that are importance for estrogen to exert its mitogenic action. The next goal will be to elucidate the mechanisms of action of these molecules in the modulation of estrogen action.

Animals↗

Role of polyamines in estradiol-induced growth of human breast cancer cells.

The present study explored the possible involvement of polyamines in estradiol-stimulated proliferation of human breast cancer cells using the estrogen-responsive subline of T-47D cells (clone 11). 17 beta-Estradiol (10(-10) M) stimulated cell growth 2- to 4-fold. This estradiol-induced proliferation was associated with a peak (at 12-24 h) of activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine biosynthesis. Estradiol-induced cell growth and ODC activity were observed only in the presence of 10% charcoal-treated fetal bovine serum, suggesting that serum factors are required for estrogen action. alpha-Difluoromethylornithine (DFMO, 0.1 mM), a specific inhibitor of ODC, blocked the estradiol-induced cell proliferation and ODC activity. Putrescine (0.1 mM) rescued the inhibitory effect of DFMO on growth of steroid-treated cells. Putrescine alone was not stimulatory to cells, and in combinations with estradiol, it did not augment the effect of estradiol. In addition, DFMO abolished the estradiol-induced growth of several other hormone-responsive cell lines but did not affect the proliferation of unresponsive cells. Hormone-responsive cells exhibited differential sensitivity to DFMO; resistant cell lines (e.g., MCF-7) were found to possess higher endogeneous levels of ODC than sensitive cell lines (e.g., T-47D and ZR-75-1). Our findings indicate that polyamines are essential, although not sufficient, in estrogen stimulation of human breast cancer cells.

Breast Neoplasms↗

Studies on biomarkers of copper exposure and toxicity in the marine amphipod Gammarus locusta (Crustacea): I. Induction of metallothionein and lipid peroxidation.

Sublethal exposures of the marine amphipod Gammarus locusta to a concentration range of copper (Cu) in water (4 days' exposure; 3, 5 and 10 micro g Cu l(-1)) or spiked sediments (28 days' exposure; 1, 3 and 6 mg Cu kg(-1) dry weight) were performed, and the resulting bioaccumulation of Cu and effects on putative metallothionein (MT) and lipid peroxidation (LP) were investigated. A time-course exposure study (over 10 days) to a single water-borne concentration of Cu (4 micro g l(-1)) was also carried out. MT and LP were quantified, respectively, by differential pulse polarography and as thiobarbituric acid-reactive malondialdehyde equivalents. The increasing levels of Cu in water and sediment exposures resulted in enhanced uptake of the metal by G. locusta. Synthesis of putative MT occurred in response to exposure to water-borne Cu, the levels being higher (p < 0.05) over the dose range of Cu compared with controls. A positive correlation was observed between putative MT levels and the Cu body-burden concentration (p < 0.001). However, no increase in LP was observed in these animals. In contrast, in the time-course experiment, LP levels increased within 1 day of exposure, subsequently peaking at 4 days (68% greater than control, p < 0.001), before returning to control values by day 6. Higher levels of MT were also observed in this exposure, but at days 6 and 10 (55% and 38%, respectively), paralleling the decrease in LP. No increase in MT levels was recorded with exposure to Cu-contaminated sediments, whereas higher levels of LP were seen in comparison with controls (p < 0.001). Overall, the inverse relationship between putative MT induction and the occurrence of LP indicates that MT may protect against the prooxidant effects of Cu. It is concluded that MT and LP offer potential for application as biomarkers in G. locusta.

Amphipoda↗

[Radioguided surgery in the treatment of gastro-entero-pancreatic neuroendocrine tumors] .

Neuroendocrine tumors are rare neoplasms. In most cases conventional imaging techniques (US,CT,RMN) are not able to identify primitive tumors. This fact conditions the approach to the treatment of these tumors. 111In-Pentetreotide scintigraphy (Octreoscan) permits to visualize occult primary tumor by somatostatin receptors, changing the clinical history of patients. This method can be used in guided surgery with a hand-held gamma probe allowing to improve the detection of occult tumor (inverse square law), giving to the patient further possibilities of survival. Intraoperative gamma probe was still utilized with success in the management of other tumors, as relapsed colorectal cancer, while reports about gamma probe in neuroendocrine tumors are poor because of the rarity of disease. In two cases we have utilized a gamma probe (ORIS model 2) in neuroendocrine tumors: in a case we have observed liver recurring localizations originating from pancreas, with high proliferative index (Ki-67 = 2033 x 10 HPF), and in a case liver metastatic carcinoid of lung. The difference between tumor and background counts was significant exceeds 2 standard deviation count rate. Gamma probe permits a radical cure in many cases and completes intraoperative ultrasound in order to provide the surgeon with other information on the intraoperative staging of the patient.

Adenocarcinoma↗

[Sepsis by Candida in VLBW neonates: therapy with liposomal Amphotericin B].

Candida spp. are recently frequent cause of nosocomial sepsis in neonates admitted in NICU, expecially VLBW. Amphotericin B is used in the treament of infections caused by Candida, but heavy side effects, expecially due to renal toxiticy, prevent often its use in the VLBW neonates. We used a new formulation of Amphotericin (AmBisome--NEXSTAR), in the treatment of 17 VLBW neonates affected by sepsis caused by Candida albicans, admitted in our NICU during two years. Twelve neonates survived, one neonate died for NEC and bowel perforation. The treatment was prolonged for 13 days (7-33 days), the total amount of dose was 65 mg/Kg, none side effect was noted.

Amphotericin B↗

[Prognostic significance of thallium-201 scintigraphy in patients with previous myocardial infarct].

With the purpose of ascertaining the predictive value of residual myocardial ischemia, in stable clinical conditions at a distance after myocardial infarction, on the incidence of late cardiac events, we evaluated 55 patients 24.2 +/- 11.4 months after myocardial infarction with thallium-201 stress test imaging. All patients were either asymptomatic or with stable effort angina pectoris, well controlled with medical treatment. In the next follow-up period, whose duration has been 22.4 +/- 14.4 months, the incidence of unfavourable cardiac events, like unstable angina, reinfarction, coronary bypass surgery, sudden cardiac death has been monitored. Thirty-one patients (56.4%) presented a reversible perfusion defect (RPD) in one or more myocardial segments; 17 of these 31 showed cardiac events during follow-up. Only 2 patients of the remaining 24 without RPD had cardiac events, with a significant difference (p less than 0.01). The patients with RPD only in peri-infarct areas had a relatively smaller number of cardiac events, with respect to those patients with RPD also or only in distant areas. Fifteen of 21 patients with RPD in 2 or more segments manifested cardiac events, compared to 2 of 10 patients with RPD in only one segment (p less than 0.01). In 10/55 patients, increased lung uptake of thallium-201 activity was observed; 8 of them presented cardiac events (p less than 0.01). This analysis confirms the high predicting value of thallium-201 RPD imaging on the incidence of cardiac events in patients controlled at a distance after myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[The PCR in gastroenterology].

The polymerase chain reaction (PCR) is a molecular biology technique that can significantly amplify DNA or RNA. With the use of recombinant DNA technology, PCR has allowed a spectrum of advances in diagnostic pathology, specially in the fields of viral diseases, hematology and genetic diseases. This work describes the basic aspects, as well as specific issues of the PCR technique. It also contains protocols and experimental conditions that are being used in our laboratory in the diagnosis of hepatitis B (HBV), hepatitis C (HCV) and in the amplification of specific sequences of the APC gene.

Base Sequence↗

[New strategies in the clinical evaluation of patients with colon cancer based on molecular studies].

During the last five years molecular studies allowed important advances in the knowledge of cancer colon with important clinical implications. The main finding was the identification and sequence analysis of the APC gen. Structural alterations of this gene have been detected in patients with Familial Adenomatous Polyposis and Gardner syndrome, which suggest a common disease. Furthermore, alterations of the APC gen appears to be also altered in cases of cancer of colon sporadic. Indicating that structural alteration of the APC gen can be inherited and/or acquired. Restriction fragment-length polymorphisms in the chromosome 5q21-22 can now be used clinically for premorbid diagnosis and counseling in familial adenomatous polyposis. The molecular studies allow the clinician to have a new approach in the management and screening of families with familial adenomatous polyposis. The sequence analysis and specific identification of the structural alteration of the APC gene is a more expensive and sophisticated study, although represent a more direct approach. In the Department of Gastroenterology of the INNSZ we are performing such molecular studies. The main purpose of our group is to proportionate integral clinical-molecular studies for families with hereditary colon cancer, create a national register of these diseases and investigate the molecular bases in order to generate new molecular diagnosis tools.

Adenomatous Polyposis Coli↗

Effect of exogenous reduced glutathione on the survival of red blood cells in hemodialyzed patients.

Reduced glutathione (GSH) is an important scavenger of free radicals in the red blood cell (RBC) membrane, and its deficiency may be a partial cause of increased hemolysis and shortened RBC survival in uremics. In this study we employed exogenous GSH (1200 mg i.v. at the end of each dialysis session for at least nine months) to treat anemia in a group of 28 hemodialyzed patients, 14 of whom were also receiving erythropoietin. RBC survival (51Cr T/2) was calculated before (26 patients) and at the end (15 pts) of GSH therapy. After the first three months anemia (RBC, hemoglobin, hematocrit, reticulocytes) improved significantly in 17 patients (60%), for as long as they were under therapy, but rapidly dropped to pre-treatment values when GSH was discontinued. The 51Cr T/2 increased significantly in responders, but not in those who did not respond. No significant differences were found between responders and non-responders as regards urea KT/V, PTH, serum iron, ferritin, dialysis membrane, dose of erythropoietin and basal 51Cr T/2. These results suggest that exogenous GSH may be a promising drug for the treatment of anemia in most hemodialyzed patients, particularly considering its low cost.

Adult↗