Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas.

OBJECTIVE: Soft tissue sarcomas (STSs) are heterogeneous tumors displaying multiple and complex molecular abnormalities with no specific pattern. Despite current therapeutic advances, the patients with STS still have a poor outcome, which makes it necessary to find out new prognostic markers. The Raf kinase inhibitory protein (RKIP) has been associated with prognosis in several human neoplasms; however, its role in STS is unknown. METHODS: In the present study RKIP expression was assessed by immunohistochemistry in a series of 87 STSs, and its expression profile was associated with the patients' pathological parameters. RESULTS: We found that RKIP is expressed in the cytoplasm of the great majority of cases, and absent in only approximately 18% of cases (16/87). Importantly, we observed that loss of RKIP expression was associated with poor outcome, constituting an independent prognostic marker. CONCLUSION: This is the first study assessing RKIP expression levels in STS. We showed that loss of RKIP expression is present in a small subset of cases; however, its absence was associated with poor survival and may be a potential marker for STS prognosis.

Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization.

BACKGROUND: Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. As other solid tumors, STSs exhibit high glucose consumption rates, associated with worse prognosis and therapeutic response. As highly glycolytic tumors, we hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs). METHODS: Immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression profiles were associated with patients' clinical-pathological parameters. RESULTS: MCT1, MCT4 and CD147 were mainly observed in the plasma membrane of cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1 nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in the plasma membrane, were associated with poor prognostic variables including high tumor grade, disease progression and shorter overall survival. Conversely, we found MCT1 nuclear expression to be associated with low grade tumors and longer overall survival. CONCLUSIONS: The present work represents the first report of MCTs characterization in STSs. We showed the original finding of MCT1 expression in the nucleus. Importantly, opposite biological roles should be behind the dual sub-cellular localization of MCT1, as plasma membrane expression of MCT1 is associated with worse patients' prognosis, while nuclear expression is associated with better prognosis.

Beneficial effects of diclofenac therapy on serum lipids, oxidized low-density lipoprotein and antioxidant defenses in rats.

To study the effects of diclofenac, a nonselective nonsteroidal anti-inflammatory drug (NSAID), on lipid profile, oxidized low-density-lipoprotein (Ox-LDL), serum antioxidant defenses and markers of oxidative stress, male Wistar rats were divided into two groups (n=10): (C) receiving intramuscularly a single daily dose of saline (NaCl 0.9%), and (AI) receiving intramuscularly a single daily dose of 10 mg/kg diclofenac sodium (C14H10Cl2NNaO2). After 28 days diclofenac-treated rats had lower Ox-LDL, apoprotein B (apo-B), apo-B/LDL-cholesterol and lipid hydroperoxide than C. Total antioxidant substances and superoxide dismutase were increased in diclofenac-treated rats, while no significant changes were observed in catalase, glutathione peroxidase and nitric oxide. A perincubation test done to examine the possibility of mechanism-based activation showed that diclofenac had no effect on maximal superoxide dismutase velocity, but significantly reduced the Michaelis-Menten (KM) constant, indicating that diclofenac induced SOD activation increasing substrate linkage affinity to the enzyme-catalytic site. In conclusion, diclofenac had beneficial effects decreasing Ox-LDL and improving antioxidant defense. It appears that the application of this agent may be feasible and beneficial for serum antioxidant protection, which certainly would bring new insights on dyslipidemia control.

Internato de clínica médica em hospital secundário: a experiência da Faculdade de Medicina de Botucatu / Internal medicine training program in a secondary hospital: the experience of the Botucatu School of Medicine

Na Faculdade de Medicina de Botucatu (FMB), os cursos de clínica médica (CM) vêm sendo tradicionalmente ministrados nas enfermarias, ambulatórios, UTI e pronto-socorro do Hospital das Clínicas da FMB, sob a supervisão do Departamento de CM. Em outubro de 2002, a FMB passou a gerenciar o Hospital Estadual Bauru (HEB), tornando possível a transferência de parte do ensino de CM no internato para hospital secundário. Desde janeiro de 2004, grupos de internato, compostos por oito alunos, passaram a estagiar em enfermaria de clínica geral do HEB, sob a supervisão de preceptores da disciplina de CM geral. Entre as vantagens decorrentes dessa mudança, citamos a possibilidade de atender doentes com patologias mais simples, maior responsabilidade com o paciente, maior contato com o preceptor e o aprendizado sobre a necessidade de cumprir metas estabelecidas pelo hospital. A principal dificuldade na execução do estágio é a sobrecarga de trabalho para os preceptores, que é causada, em parte, pela ausência de residentes na enfermaria. Consideramos que a experiência em transferir parte do internato de CM para hospital secundário foi bem-sucedida e esta pode vir a estimular outras áreas da FMB para a busca de novos cenários de ensino.

In the Botucatu School of Medicine (BSM), the internal medicine course has traditionally been run in the infirmaries, out-patient clinics, emergency unit, and intensive care unit of the BSM Hospital under the supervision of the Internal Medicine Department. In October 2002, BSM took over the management of the Bauru State Hospital (BSH) making possible to transfer part of the internal medicine training program to a secondary level hospital. Since January 2004, groups of eight students have stayed for a training program at the BSH Internal Medicine Infirmary under the supervision of internal medicine teaching doctors. Advantages of this scheme include exposing students to the simpler pathologies found in the general population, more responsibility with the patient, more contact between student and teacher, and learning about the need to reach the goals set by the hospital. The main functional difficulty of this training program is the heavy workload the teaching doctors have to face, in part due to the absence of residents in the infirmary. In conclusion, we consider the experience of transferring part of internal medicine training program to a secondary hospital has been a success and capable of stimulating other medical disciplines in the BSM to look for new settings for their training programs.