Estudo da ação citotóxica de drogas antineoplásicas associadas ou não à dexametasona sobre as células de mastocitoma murino (linhagem p-815)

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Survival and Histopathological Study of Animals Bearing Ehrlich Tumor Treated With a Rhodium(II) Amidate.

The survival of 90% of a tumor-bearing population treated with the complex Rh(2) (CF(3)CONH)(4) was examined and the pharmacological parameter Surv(90) determined. Histopathological alterations raised for this drug in several tissues were studied in Balb-c mice. A Surv(90) dose of 3.8x 10(-5) mol/kg was found.

Water Soluble Cyclophosphamide Adducts of Rhodium(II) Keto-Gluconate and Glucuronate. Synthesis, Characterization and In Vitro Cytostatic Assays.

The synthesis, characterization and biological assays of two new rhodium carboxylate sugar derivatives and respective cyclosphosphamide adducts are described. The compounds, characterized by (13)C and (1)H NMR, infrared and UV-visible spectra, presented high water solubility and hydration grades were confirmed given the concordance between thermal and CHN analyses. The adducts were active in vitro against K-562 cells.

Growth and differentiation of bone marrow hematopoietic cells in mice bearing Ehrlich ascite tumor and treated with Dicyclopentadienildichlorotitanium (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 DDCT-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.

Distribution of rhodium in mice submitted to treatment with the adduct of rhodium propionate and sodium isonicotinate.

The distribution of rhodium in Balb/c mice following intraperitoneal (ip) administration of a solution of adduct of rhodium propionate and sodium isonicotinate has been investigated. The metal concentration was determined in blood and in the following organ tissues: brain, heart, lung, liver, spleen, kidney, testes, and uterus/ovary, and the rhodium concentration was obtained by Inductively Coupled Argon Atomic Emission Spectroscopy (ICP-AES). The metal was detected in all organ tissues examined, mainly in spleen, liver, uterus/ovary and heart. Nine days after the injection, traces of rhodium were found in the liver and kidneys and, twenty days after the injection, only in the liver.

Rh(2)(CF(3)CONH)(4): The First Biological Assays of a Rhodium (II) Amidate.

The rhodium (II) complexes Rh(2)(tfa)(4).2(tfac) and Rh(2)(tfacam)(4) (tfacam = CF(3)CONH-,tfa = CF(3)COO-,tfac = CF(3)CONH(2)) were synthesized and characterized by microanalysis and electronic and vibrational spectroscopies. Rh(2)(tfacam)(4) was tested both in vitro (U937 and K562 human leukemia cells and Ehrlich ascitic tumor cells) and in vivo for cytostatic activity and lethal dose determination, respectively. This is the first rhodium tetra-amidate to have its biological activity evaluated. The LD(50) value for Rh(2)(tfacam)(4) is of the same order as that of cisplatin, and it was verified that the rhodium complex usually needs lower doses than cisplatin to promote the same inhibitory effects.

Water-soluble rhodium(II) carboxylate adducts: cytotoxicity of the new compounds.

Rhodium(II) carboxylate (acetate, propionate, and butyrate) adducts with isonicotinic acid (Hisonic) were prepared for study. Elemental analyses and electronic spectroscopy show that the adducts contain two isonicotinic acid ligands coordinated in the axial position at the pyridinic nitrogen. The in vitro (K562 human leukemic cell line) assay and LD10 in mice results, in addition to tests of solubility, suggest that, in the presence of blood lipids or cellular membrane, the adducts dissociate into the parent compounds and the rhodium(II) carboxylate enters the cell to carry out its biological effects.

Mononuclear cell cytotoxicity in rats with Walker 256 tumor.

In the present study we characterized the cytotoxicity of Wistar rat mononuclear cells from 21 animals which received 10(6) Walker 256 tumor cells by the subcutaneous route. All animals developed the tumor. Cytotoxicity was studied 15 days after inoculation using spleen, thymus and lymph node T lymphocytes as well as macrophages from the peritoneal cavity. A Walker 256 tumor cell suspension and tumor cells in culture (YAC-1) were labelled with 51Cr and used as target cells, according to the Herberman technique and a gamma counter was used for counting. Anti-Walker cell cytotoxicity was significantly decreased in T lymphocytes from the spleen (9.6% vs 51.1% for the control) and thymus (11.5% vs 38.2% for the control), whereas no difference was observed for lymph nodes (41.2% vs 49.5% for the control) or macrophages (43.4% vs 46.3% for the control). Anti-YAC-1 cytotoxicity was significantly decreased in T lymphocytes from all lymphoid organs compared to control: 23.6% vs 42.8% for the spleen, 22.6% vs 41.1% for the thymus, 26.6% vs 42.1% for lymph nodes, and 27.1% vs 46.3% for macrophages. No correlation was observed between tumor weight, and anti-Walker cytotoxicity or anti-YAC-1 cytotoxicity.

Mononuclear cell cytotoxicity in rats with Walker 256 tumor

In the present study we characterized the cytotoxicity of Wistar rat mononuclear cells from 21 animals which received 10(6) Walker 256 tumor cells by the subcutaneous route. All animals developed the tumor. Cytotoxicity was studied 15 days after inoculation using spleen, thymus and lymph node T lymphocytes as well as macrophages from the peritoneal cavity. A Walker 256 tumor cell suspension and tumor cells in culture (YAC-1) were labelled with 51Cr and used as target cells, according to the Herberman technique and a gamma counter was used for counting. Anti-Walker cell cytotoxicity was significantly decreased in T lymphocytes from the spleen (9.6 vs 51.1 for the control) and thymus (11.5 vs 38.2 for the control), whereas no difference was observed for lymph nodes (41.2 vs 49.5 for the control) or macrophages (43.4 vs 46.3 for the control). Anti-YAC-1 cytotoxicity was significantly decreased in T lymphocytes from all lymphoid organs compared to control: 23.6 vs 42.8 for the spleen, 22.6 vs 41.1 for the thymus, 26.6 vs 42.1 for lymph nodes, and 27.1 vs 46.3 for macrophages. No correlation was observed between tumor weight, and anti-Walker cytotoxicity or anti-YAC-1 cytotoxicity.

Antitumor effects of rhodium (II) complexes on mice bearing Ehrlich tumors.

Rhodium (II) trifluoroacetate (TFARh), rhodium (II) trifluoroacetate adduct with sulfadiazine (TFARh.Sd) and rhodium (II) acetate adduct with sulfisoxazole (RhSx) were tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and for viability of Ehrlich tumor cells in culture. At ip doses up to 60 mumol/kg (40-70 and 59 mg/kg, respectively), these compounds had no toxic effects up to 14 days. At ip doses of 10 mumol kg-1 day-1 for 5 days, TFARh and TFARh.Sd significantly increased the survival rate of mice bearing Ehrlich ascites cells (probability of survival to the end of 34th day, controls = 0.23, TFARh = 0.85, TFARh.Sd = 0.74). No significant effect was observed for RhSx. In vitro, these rhodium complexes at 40 microM significantly increased the number of dead cells in cultured Ehrlich tumor cells.

Antitumor effects of rhodium (II) complexes on mice bearing Ehrlich tumors

Rhodium (II) trifluoracetate (TFARh), rhodium (II) trifluoracetate adduct with sulfadiazine (TFARh.Sd) and rhodium (II) acetate adduct with sulfisoxazole (RhSx) were tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and for viability of Ehrlich tumor cells in culture. At ip doses up to 60 µmg/kg (40-70 and 59 mg/kg, respectively), these coumpounds had no toxic effects up to 14 days. At ip doses of 10 µmol Kg-1 day-1 for 5 days, TFARh and TFARh.Sd significantly increased the survival rate of mice bearing Ehrlich ascites cells (probability of survival to the end of 34th day, controls = 0.23, TFARh = 0.85, TFARh.Sd = 0.74). No significant effect was observed for RhSx. In vitro, these rhodium complexes at 40 µM significantly increased the number of dead cells in cultured Ehrlich tumor cells

[Action of 3,5,3'-triiodothyronine (T3) on Walker's 256 carcinosarcoma development]. / Ação da 3,5,3'-triiodotironina (T3) sobre a evolução do carcinossarcoma 256 de Walker.

In order to verify the effects of triiodothyronine (T3) administration in animals bearing Walker tumor, the authors have carried out an experimental study utilizing Wistar rats inoculated with both ascitic and solid Walker tumor, and Balb/c isogenic mice for the study of spreading of macrophages. The animals were treated with T3 20 micrograms/100 g of body weight and the data were analysed by Chi-square and Mann-Whitney tests. The authors conclude that T3 increases significantly the survival of rats bearing Walker tumor, and the spreading of macrophages when inoculated into the peritoneal cavity of mice. The hormone does not alter the weight of tumor mass. These results could be explained by the macrophageal activation and by the synthesis of the tumor necrosis factor.

Antitumor effects of rhodium (II) citrate in mice bearing Ehrlich tumors.

Rhodium II citrate was tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and inhibition of DNA synthesis by Ehrlich tumor, malignant adrenocortical cells (Y-1) and normal adrenocortical cells (AR-1). At ip doses up to 260 mg/kg, the compound had no toxic effects for up to 14 days. The same total dose given over 4 days significantly increased the survival rate of mice bearing Ehrlich ascites cells. Thymidine incorporation by Ehrlich tumor, Y-1 and AR-1 cells in vitro was inhibited 50% by 0.1 to 0.2 mM concentrations of the compound. We conclude that the increased survival of the tumor-bearing mice was due at least in part to the inhibition of DNA synthesis with a consequent reduction of cell division and tumor growth.

Antitumor effects of Rhodium (II) citrate in mice bearing Chrlich tumors

Rhodium II citrate was tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and inhibition of DNA synthesis by Ehrlich tumor, malignant adrenocortical cells (Y-1) and normal adrenocortical cells (AR-1)_. At ip doses up to 260 mg/Kg, the compound had no toxic effects for up to 14 days. The same total dose given over 4 days significantly increased the survial rat of mice bearing Ehrlich ascites cells. Thymidine incorporation by Ehrlkich tumor, Y-1 cells in vitro was inhibited 50% by a.1 to 0.2 mM concentrations of the compound. We conclude that the increase survival of the tumor-bearing mice was due at least in part to the inhibition of DNA synthesis with a consequet reduction of cell division and tumor growth

Practical approaches to screening for cervical cancer.

The Program of the Fundação "Centro de Pesquisa de Oncologia" (FCPO) and the Instituto Brasileiro de Controle do Câncer (IBCC) in São Paulo has examined 980,977 women from 1970 to September 1985. Dysplasias, in situ, and invasive carcinomas were detected in 15,123 women (1.5%). The rates of false-negative and false-positive cytologic diagnoses of the program are 2.3% and 27%, respectively. The following epidemiological variables were evaluated: age, parity, age at first sexual intercourse, age at first pregnancy, education, and age at menarche. It was found that women at higher risk for cervical carcinoma in this population were those 26 years of age or older, with 4 or more pregnancies, women who had the first coitus before 18 years of age, and the first complete pregnancy before 19, as well as illiterate women or those who did not complete the first 4 years of primary school. In Brazil, the frequencies of cervical carcinomas are 25.8% for in situ and 72.2% for invasive (0.4 to 1). In this program, the corresponding percentages are 61.0% for in situ and 39.0% for invasive carcinomas (1.6 to 1). Including dysplasias, the percentages for Brazil are 56.3% for severe dysplasias plus in situ carcinomas and 43.7% for invasive carcinomas (1.3 to 1). In the FCPO/IBCC Program these percentages are 83.2% and 16.8% (5 to 1).

Qualitative erythrocyte enzymatic disorder in Ehrlich tumor-bearing mice.

Erythrocyte glutathione reductase Michaelis-Menten constant was found to be significantly increased in Ehrlich tumour bearing mice, indicating a clear qualitative disturbance due to a neoplastic process. No changes were observed in glucose-6-phosphate dehydrogenase.

Acquired disturbance of erythrocyte glutathione reductase in experimental tumors.

Erythrocyte glutathione reductase activity was assayed in animals bearing Walker, Ehrlich, and Krebs tumors, 21 days after implantation. It was noticed that the activity was significantly enhanced in all three tumors.

Aspectos basicos das linhagens celulares mais utilizadas. / Culture characteristics of some cell lines

Sao apresentados alguns aspectos basicos das linhagens celulares mais utilizadas nos nossos laboratorios de pesquisas. Quatro linhagens de origem humana e tres linhagens de origem animal sao descritas quanto a sua obtencao, meio de congelamento, meio de cultura, caracteristicas de crescimento e morfologia