Casearin X, Its Degradation Product and Other Clerodane Diterpenes from Leaves of Casearia sylvestris: Evaluation of Cytotoxicity against Normal and Tumor Human Cells

An EtOH extract of the leaves of Casearia sylvestris afforded new clerodane diterpene, casearin X, together with the known compounds casearins B, D, L, and O, and caseargrewiin F Casearin X degraded to the corresponding dialdehyde when stored in CDCl(3). The diterpenes isolated were cytotoxic to human cancer cell lines, with caseargrewiin F being the most active and the new clerodane, casearin X, the second active compound with IC(50) values comparable to the positive control doxorubicin. All isolated diterpenes showed lower activities against normal human cells than against cancer cell lines, which might indicate a possible selective action on cancer cells. Casearin X dialdehyde was not cytotoxic to cancer cells indicating that the occurrence of these CO groups at C(18) and C(19) is incompatible with the cytotoxic activity.

Expressão da p53 no tumor e no epitélio oral em pacientes com câncer de boca e faringe

INTRODUÇÃO: Expressiva porcentagem de pacientes com carcinomas de boca e faringe apresentam superexpressão da proteína p53 induzida por tabaco, álcool e radioterapia. OBJETIVO: Descrever a expressão da p53 em áreas de mucosa normal adjacente ao tumor e em carcinomas da boca e faringe. MÉTODO: Estudo prospectivo, com seguimento clínico por um ano, de 24 pacientes com câncer espinocelular de boca e faringe. Foram feitas biópsias na neoplasia e em áreas de mucosa normal adjacente ao tumor, antes e 9 meses após a radioterapia, e realizado estudo imunohistoquímico da expressão da p53. RESULTADOS: Antes da radioterapia, houve alteração da expressão da p53 em 20 das 24 biópsias feitas na neoplasia e em 14 nas de mucosa normal adjacente ao tumor. Onze paciente morreram antes de 1 ano de seguimento clínico. Dos 2 pacientes iniciais com aumento da p53 após a radioterapia continuava aumentada em 7 na área da neoplasia e em 6 nas áreas de mucosa normal. Observou-se associação da p53 com o tabagismo e estádio do tumor (p < 5%) mas não com o grau de diferenciação celular e alcoolismo. CONCLUSÃO: O aumento da expressão da p53 foi observado tanto na área da neoplasia como em mucosa normal na maioria dos pacientes com carcinoma de boca e faringe antes e após a radioterapia. Houve correlação estatisticamente significante da expressão da p53 com o tabagismo e estádio da neoplasia.

Tumor hepático experimental (VX-2) em coelho: implantação do modelo no Brasil

Os estudos para a investigação de novas modalidades terapêuticas em biologia tumoral, deveriam passar por estudos experimentais prévios. Neste sentido dispõem-se hoje de uma grande variedade de modelos tumorais experimentais; em determinadas investigações faz-se necessária a adequação do modelo tumoral às necessidades biológicas, patológicas e experimentais dos estudos. Desta forma, em nosso serviço, buscávamos um modelo tumoral hepático para estudos experimentais que se adequasse às seguintes características: fácil manipulação, crescimento controlável, evolução e agressividade semelhantes aos seres humanos. Os dados da literatura nos levaram a busca do tumor hepático VX-2, em coelhos. Neste artigo discutimos as vantagens da utilização deste modelo experimental e a sua introdução em nosso país.

Ascite neoplásica: efeito da solução aquosa de fenol, ácido acético e glicerina sobre o tumor ascítico de Ehrlich

OBJETIVO: Verificar o efeito da solução composta por fenol, ácido acético e glicerina sobre o tumor ascítico de Ehrlich. MÉTODOS: Utilizou-se 283 camundongos divididos em 2 protocolos (animais portadores e não portadores de tumor) procedendo-se a injeção de 0,25 ml, 0,10 ml e 0,05 ml da solução teste e 0,25 ml de solução salina, o sacrifício foi realizado após 3 e 6 dias do tratamento, analisando, a seguir, a contagem diferencial de células presentes no líquido ascítico. RESULTADOS: Observou-se que nos animais portadores de tumor houve uma redução significante do número de células tumorais e aumento do número de células inflamatórias, nos animais sem tumor observou-se influxo de células inflamatórias para a cavidade peritoneal. CONCLUSÃO: A solução proposta causa, in vivo, a diminuição do número de células tumorais e aumento do número de células inflamatórias no líquido ascítico.

Efeito da solução aquosa de fenol, ácido acético e glicerina sobre o tumor ascítico de Ehrlich: estudo experimental in vitro

OBJETIVO: Verificar o efeito da solução composta por fenol, ácido acético e glicerina sobre o tumor ascítico de Ehrlich. MÉTODOS: Após a coleta do líquido ascítico de três camundongos procedeu-se a incubação, a 37° C, do mesmo com diferentes doses da solução teste (0,50, 0,25, 0,10 e 0,05 ml) e com solução salina (0,50 ml como controle; estudou-se a viabilidade celular pela técnica de exclusão do azul tripan). RESULTADOS: Observou-se que ao final de 15 minutos todas as células tumorais encontravam-se inviáveis com as diferentes doses da solução teste. CONCLUSÃO: A solução proposta, causa, in vitro, a morte das células tumorais ao foral de 15 minutos.

Tumor venéreo transmissível com metástases cutâneas em um cão transmissible venereal

O tumor venéreo transmissível é diagnosticado, na maioria das vezes, em animais jovens, sadios e sexualmente ativos. Acomete, comumente, a genitália externa. Metástases, apesar de incomuns, ocorrem. O presente trabalho relata um caso de tumor venéreo transmissível na glande peniana com disseminação para a pele das regiões abdominal e inguinal.

TELOMERIC FUSIONS IN A WILMS-TUMOR

The present report describes the karyotypic findings in cells from a Wilms' tumor. The most consistent cytogenetic abnormalities detected consisted of translocations involving break and fusion of chromosomal telomeres and telomeric associations frequently affecting the terminus of the short arms of chromosomes 14 and 17.

Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

Background: It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle.Methods: To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein):pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine):leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption.Results: Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups.Conclusions: Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones.

Growth and differentiation of bone marrow hematopoietic cells in mice bearing Ehrlich ascite tumor and treated with Dicyclopentadienildichiorotitanium (IV)

In this work we have:investigated the growth and differentiation of bone marrow stem cells in mice bearing Ehrlich ascites tumor-and treated with three dose-regimens of Dicyclopentadienyldichlorotitanium (IV) (DDCT). We also: studied the presence of colony stimulating factors In the serum of PDCT-treated animals as well-as the effects-of the drug on the survival of the tumor-bearing mice. The-results demonstrated that the myelosuppression developed in the tumor-bearing animals is prevented by the administration:of 1, 2 or 3 doses of 15 mg/kg DDCT. In the treatment with three doses, however, 23 % of the animals died. Moreover, DDCT treatment in normal animals resulted in increased numbers of CFU-GM. We observed the presence of stimulating factors in the serum of drug-treated animals which induced the growth and differentiation of bone marrow progenitor cells from normal animals in vitro. on the other hand, in vitro addition of the drug to these cultures had no effect. Thus, we conclude that the drug protects against the myelosuppression induced by the tumor and that this protection may be related to an indirect action of the drug. (C) 1998 International Society for Immunopharmacology. Published by Elsevier B.V. Ltd.

EARLY ACTIVATION OF SPLENIC MACROPHAGES BY TUMOR-NECROSIS-FACTOR-ALPHA IS IMPORTANT IN DETERMINING THE OUTCOME OF EXPERIMENTAL HISTOPLASMOSIS IN MICE

Experimental infection of animals with Histoplasma capsulatum caused a massive macrophage infiltration into the spleen and induced the production of tumor necrosis factor alpha (TNF-alpha) locally. The cytokine was also produced in vitro by peritoneal exudate macrophages exposed to a large inoculum of yeast cells. Depletion of the cytokine by injection of polyclonal sheep anti-TNF-alpha antibody was detrimental to sublethally infected mice. Fungous burdens in the spleens of TNF-alpha-depleted mice were higher than they were in the infected control mice at days 2, 7, and 9 after infection, and the antibody-treated animals succumbed to the infection. Histopathological study of spleen sections revealed that splenic macrophages were not able to control proliferation of intracellular yeasts as a result of TNF-alpha depletion. It seems that TNF-alpha plays a role in early activation of splenic macrophages which is important in controlling the outcome of an infection.

Differential regulation of the release of tumor necrosis factor-alpha and of eicosanoids by mast cells in rat airways after antigen challenge

Background: Rat trachea display a differential topographical distribution of connective tissue mast cells (CTMC) and mucosal mast cells (MMC) that may imply regional differences in the release of allergic mediators such as tumor necrosis factor-alpha (TNF-alpha) and eicosanoids.Aim: To evaluate the role of CTMC and MMC for release of TNF-alpha and eicosanoids after allergenic challenge in distinct segments of rat trachea.Materials and methods: Proximal trachea ( PT) and distal trachea (DT) from ovalbumin (OVA)-sensitized rats, treated or not with compound 48/80 ( 48/80) or dexamethasone, were incubated in culture medium. After OVA challenge, aliquots were collected to study release of TNF-alpha and eicosanoids.Results: Release of TNF-alpha by PT upon OVA challenge peaked at 90 min and decayed at 6 and 24 h. Release from DT peaked at 30-90 min and decayed 6 and 24 h later. When CTMC were depleted with 48/80, OVA challenge exacerbated the TNF-alpha release by PT at all time intervals, while DT exacerbated TNF-alpha levels 6 and 24 h later only. Dexamethasone reduced TNF-alpha production after 90 min of OVA challenge in PT and at 3 and 6h in DT. OVA challenge increased prostaglandin D-2 in DT and leukotriene B-4 in both segments but did not modify prostaglandin E-2 and leukotriene C-4 release.Conclusion: OVA challenge induces TNF-alpha release from MMC, which is negatively regulated by CTMC. The profile of TNF-alpha and eicosanoids depends on the time after OVA challenge and of the tracheal segment considered.