Diagnóstico, estadiamento e tratamento cirúrgico do adenocarcinoma de pâncreas

O adenocarcinoma pancreático é um dos tumores sólidos de pior prognóstico, sendo o tratamento cirúrgico o único potencialmente curativo. Na grande maioria dos pacientes o tumor é diagnosticado em fase avançada, comumente na presença de doença metastática. A introdução de modernos métodos diagnósticos associados ao aperfeiçoamento dos já existentes tem gerado controvérsia quanto à melhor maneira de se estabelecer o diagnóstico e estadiamento do tumor. Da mesma forma, o papel da cirurgia na paliação e aspectos técnicos da ressecção de lesões localizadas estão longe de alcançarem consenso na prática. Método - Revisão da literatura sobre os aspectos controversos relacionados ao tema e um algoritmo para a abordagem dos pacientes com suspeita de tumor de pâncreas são apresentados. Foram utilizados os descritores: “adenocarcinoma” e “pâncreas” para pesquisa no PubMed (www.pubmed.com) e na Bireme (www.bireme.br) e a seguir selecionadas as publicações pertinentes a cada tópico escolhido com atenção especial para metanálises, estudos clínicos controlados, revisões sitemáticas e ainda publicações de grandes centros especializados em doenças pancreáticas. Conclusões - Na suspeita de adenocarcinoma de pâncreas é possível realizar estadiamento muito próximo do real sem a necessidade da exploração cirúrgica sistemática em virtude da disponibilidade na prática de exames modernos e eficientes. Isso permite que paliação menos invasiva seja praticada na maioria dos pacientes com lesões avançadas e incuráveis. Nos em que a cura é possível, a operação deve ser realizada objetivando-se, essencialmente, a remoção da lesão com margens livres e com aceitáveis índices de morbi-mortalidade

A Catalytically Inactive Lys49 PLA2 Isoform from Bothrops jararacussu venom that Stimulates Insulin Secretion in Pancreatic Beta Cells

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Reactivity of p53 protein in canine transmissible venereal tumor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Aspectos clínico e cirúrgicos do tumor mamário canino: clinical and surgical evolution

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

INTRAOCULAR TRANSMISSIBLE VENEREAL TUMOR IN A DOG

Tumor venéreo transmissível (TVT) é uma neoplasia de células redondas que acomete a mucosa genital externa de cães, machos e fêmeas. A transmissão decorre da implantação de células tumorais durante o coito, brigas ou interações entre animais portadores e susceptíveis. Existem relatos referindo-se a localizações atípicas do TVT, mas metástases raramente ocorrem. O presente relato descreve um caso incomum de TVT, com acometimento intra-ocular e metástases nos linfonodos ingüinais, num cão Terrier Brasileiro, com seis anos de idade. O animal apresentava massas anormais de tecido no olho direito, extremidade do pênis e aumento de volume de linfonodos da região ingüinal. A histopatologia do globo ocular e as citologias da massa peniana e dos nódulos subcutâneos evidenciaram aspectos citológicos semelhantes, caracterizados por células redondas com núcleo grande e nucléolo proeminente localizado centralmente. O citoplasma apresentou-se pálido e com presença de vacúolos pequenos e arredondados. O diagnóstico de TVT com acometimento intra-ocular e metástases em linfonodos foi baseado nos achados clínicos, citológicos e histopatológicos.

Expressão da E-caderina em carcinoma de células escamosas e no tumor de células basais de cães

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Immunological response in mice bearing LM3 breast tumor undergoing Pulchellin treatment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of Yersinia pseudotuberculosis outer proteins (Yops) on interleukin-12, tumor necrosis factor alpha and nitric oxide production by peritoneal macrophages

An essential key to pathogenicity in Yersinia is the presence of a 70 kb plasmid (pYV) which encodes a type-III secretion system and several virulence outer proteins whose main function is to enable the bacteria to survive in the host. Thus, a specific immune response is needed in which cytokines are engaged. The aim of this study was to assess the influence of Yersinia outer proteins (Yops) released by Yersinia pseudotuberculosis on the production of the proinflammatory cytokines, interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-alpha), and nitric oxide (NO) by murine peritoneal macrophages. To this end, female Swiss mice were infected intravenously with wild-type Y pseudotuberculosis or with mutant strains unable to secrete specific Yops (YopE, YopH, YopJ, YopM, and YpkA). on the 7th, 14th, 21st, and 28th days after infection, the animals were sacrificed and the cytokines and NO were assayed in the peritoneal macrophages culture supernatants. A fall in NO production was observed during the course of infection with all the strains tested, though during the infection with the strains that did not secrete YopE and YopH, the suppression occurred later. There was, in general, an unchanged or sometimes increased production of TNF-alpha between the 7th and the 21st day after infection, compared to the control group, followed by an abrupt decrease on the last day of infection. The IL-12 production was also suppressed during the infection, with most of the strains tested, except with those that did not secrete YopJ and YopE. The results suggest that Yops may suppress IL-12, TNF-alpha, and NO production and that the most important proteins involved in this suppression are YopE and YopH. (C) 2004 Elsevier B.V. All rights reserved.

Effect of the essential oil of Achillea millefolium L. in the production of hydrogen peroxide and tumor necrosis factor-alpha in murine macrophages

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tetracaine stimulates insulin secretion through the mobilization of Ca2+ from thapsigargin- and IP3-insensitive Ca2+ reservoir in pancreatic beta-cells

The effect of tetracaine on Ca-45 efflux, cytoplasmic Ca2+ concentration [Ca2+](i), and insulin secretion in isolated pancreatic islets and beta-cells was studied. In the absence of external Ca2+, tetracaine (0.1-2.0 mM) increased the Ca-45 efflux from isolated islets in a dose-dependant manner. Tetracaine did not affect the increase in Ca-45 efflux caused by 50 mM K+ or by the association of carbachol (0.2 mM) and 50 mM K+. Tetracaine permanently increased the [Ca2+](i) in isolated beta-cells in Ca2+-free medium enriched with 2.8 mM glucose and 25 mu M D-600 (methoxiverapamil). This effect was also observed in the presence of 10 mM caffeine or 1 mu M thapsigargin. In the presence of 16.7 mM glucose, tetracaine transiently increased the insulin secretion from islets perfused in the absence and presence of external Ca2+. These data indicate that tetracaine mobilises Ca2+ from a thapsigargin-insensitive store and stimulates insulin secretion in the absence of extracellular Ca2+. The increase in Ca-45 efflux caused by high concentrations of K+ and by carbachol indicates that tetracaine did not interfere with a cation or inositol triphosphate sensitive Ca2+ pool in beta-cells.

Dexamethasone-induced insulin resistance is associated with increased connexin 36 mRNA and protein expression in pancreatic rat islets

Augmented glucose-stimulated insulin secretion (GSIS) is an adaptive mechanism exhibited by pancreatic islets from insulin-resistant animal models. Gap junction proteins have been proposed to contribute to islet function. As such, we investigated the expression of connexin 36 (Cx36), connexin 43 (Cx43), and the glucose transporter Glut2 at mRNA and protein levels in pancreatic islets of dexamethasone (DEX)-induced insulin-resistant rats. Study rats received daily injections of DEX (1 mg/kg body mass, i.p.) for 5 days, whereas control rats (CTL) received saline solution. DEX rats exhibited peripheral insulin resistance, as indicated by the significant postabsorptive insulin levels and by the constant rate for glucose disappearance (K-ITT). GSIS was significantly higher in DEX islets (1.8-fold in 16.7 mmol/L glucose vs. CTL, p < 0.05). A significant increase of 2.25-fold in islet area was observed in DEX vs. CTL islets (p < 0.05). Cx36 mRNA expression was significantly augmented, Cx43 diminished, and Glut2 mRNA was unaltered in islets of DEX vs. CTL (p < 0.05). Cx36 protein expression was 1.6-fold higher than that of CTL islets (p < 0.05). Glut2 protein expression was unaltered and Cx43 was not detected at the protein level. We conclude that DEX-induced insulin resistance is accompanied by increased GSIS and this may be associated with increase of Cx36 protein expression.

Low protein diet confers resistance to the inhibitory effects of interleukin1 beta on insulin secretion in pancreatic islets

High protein content in the diet during childhood and adolescence has been associated to the onset insulin-dependent diabetes mellitus. We investigated the effect of interleukin-1 beta (IL-I beta) on insulin secretion, glucose metabolism, and nitrite formation by islets isolated from rats fed with normal protein (NP, 17%) or low protein (LP, 6%) after weaning. Pretreatment of islets with IL-1 beta for 1 h or 34 h inhibited the insulin secretion induced by glucose in both groups, but it was less marked in LP than in NP group. Islets from LP rats exhibited a decreased IL-1 beta -induced nitric oxide (NO) production, lower inhibition of D-[(UC)-C-14]-glucose oxidation to (CO2)-C-14, and less pronounced effect of IL-1 beta on alpha -ketoisocaproic acid-induced insulin secretion than NP islets. However, when the islets were stimulated by high concentrations of K+ the inhibitory effect of IL-1 beta on insulin secretion was not different between groups. In conclusion, protein restriction protects beta -cells of the deleterious effect of IL-1 beta, apparently, by decreasing NO production. The lower NO generation in islets from protein deprived rats may be due to increased free fatty acids oxidation and consequent alteration in Ca2+ homeostasis. (C) 2001 Elsevier B.V. All rights reserved.

Modulation of macrophage cytokine profiles during solid tumor progression: susceptibility to Candida albicans infection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)