Actividad antitumoral de biopolímeros aislados de Vibrio sp. en cáncer de mama inducido en ratas / Antitumor activity of vibrio sp. isolated biopolymers in induced breast cancer in rats

RESUMEN Objetivo: Evaluar la actividad antitumoral del extracto crudo de biopolímeros aislados de la bacteria marina Vibrio sp. en cáncer de mama inducido por N-Methyl-N-nitrosourea (MNU) en ratas. Materiales y métodos: Se cultivó la bacteria marina Vibrio sp. durante siete días, luego se filtró, precipitó y concentró el sobrenadante crudo. Se administró una dosis única de MNU 50 mg/kg a 39 ratas Holtzman y fueron tratadas diariamente durante nueve semanas por vía oral: G1 (n=13): suero fisiológico 0,1 mL/100g; G2 (n=13): extracto crudo de biopolímeros de Vibrio sp. 20 mg/kg; G3 (n=13): tamoxifeno 100 mg/kg. El G4 (n=11) solo recibió suero fisiológico 0,1 mL/100g. Se valoró semanalmente el peso corporal y la aparición de tumores mamarios identificados mediante palpación; así como el examen histopatológico al final del tratamiento. Resultados: El 77% de las ratas del grupo G1 desarrollaron tumores a partir de la séptima semana en un promedio de 2,2 tumores por cada animal; en contraste al grupo tratado con el extracto crudo de biopolímeros y tamoxifeno; donde solo una rata (8%) en cada grupo desarrolló tumores y posterior a la semana nueve de la inducción (p=0,001). Los resultados histopatológicos sostienen que todos los tumores extirpados corresponden a adenocarcinoma ductal de mama con distintos patrones: sólido, papilar y quístico. Asimismo, se evidenciaron focos necróticos en el 30% de los tumores del grupo G1. Conclusión: El extracto crudo de biopolímeros aislados de Vibrio sp. presentan efecto antitumoral en cáncer de mama inducido en ratas.

ABSTRACT Objective: To evaluate the antitumor activity of the raw extract from biopolymers isolated from the Vibrio sp. marine bacteria in breast cancer induced by N-Methyl-N-nitrosourea (MNU) in rats. Materials and methods: The Vibrio sp. marine bacteria was cultured for seven days, then the raw supernatant was filtered, precipitated and concentrated. MNU was administered in a single dose of 50 mg/kg to 39 Holtzman rats and were daily treated for 9 weeks orally: G1 (n = 13): 0.1 mL/100 g of saline solution; G2 (n = 13): 20 mg/kg of raw extract from Vibrio sp. biopolymers; G3 (n = 13): 100 mg/kg of tamoxifen; G4 (n = 11) received no MNU and only 0.1 mL/100 g of saline solution. Body weight and the appearance of breast tumors identified by palpation were assessed weekly, as well as histopathological examination at the end of treatment. Results: Seventy-seven percent of the rats in the G1 group developed tumors from week 7 onwards in an average of 2.2 tumors per animal; in contrast to the group treated with the raw biopolymer extract and tamoxifen; where only one rat (8%) in each group developed tumors after week nine of induction (p = 0.001). The histopathological results support that all the removed tumors correspond to breast ductal adenocarcinoma with different patterns: solid, papillary and cystic. Likewise, necrotic foci were evidenced in 30% of the tumors of the G1 group. Conclusion: The raw extract of biopolymers isolated from Vibrio sp. present antitumor effect in breast cancer induced in rats.

Chemical carcinogenesis by DMBA (7, 12-dimethylbenzanthracene) in female BALB/c mice: new facts / Carcinogenese quimica por DMBA (7, 12-dimethylbenzanthracene) em camundongos femeas BALB/c: novos fatos

Polycyclic aromatic hydrocarbons are known carcinogens used in rodent experimental models. In this study, the carcinogen DMBA (7,12-dimethylbenzanthracene) was administered by gavage, diluted in corn oil, to female BALB / c mice at hebdomadary doses of 1 mg per animal for 1, 3, 6 or 9 weeks. Animals were weighed and monitored weekly until death. Remaining animals were euthanized at the age of 53 weeks. At necropsy, representative fragments of neoplasms were collected and routinely processed for histopathological analysis. Of all mice that received DMBA, 68.57% developed some type of tumor. Of the 70 mice treated with various doses of DMBA, 22 (31.43%) developed mammary tumors. The adenoacanthoma was the most commonly (18.75%) diagnosed histological type of breast cancer. Lung (15.71%), lymphoid tissue (11.43%), stomach (7.14%) and skin (2.86%) were also primary sites of tumor development. One third (33.33%) of the mice receiving 1 mg of DMBA developed lung cancer. Therefore, the administration of DMBA was shown to be an efficient model of carcinogenesis in mice, especially for the study of breast cancer, when using the highest dose, and lung, when using the lowest dose. Carcinogenesis models have been used for several purposes in cancer research. These results represent new facts for a classic carcinogenesis model.

Hidrocarbonetos policíclicos e aromáticos são carcinógenos usados em modelos experimentais em roedores. Neste estudo, o carcinógeno DMBA (7,12-dimetilbenzantraceno) foi administrado por gavagem, diluído em óleo de milho, para camundongos BALB/c em doses hebdomadárias de 1 mg por animal por 1, 3, 6 ou 9 semanas. Os animais foram pesados e monitorados semanalmente até a morte. Os animais remanescentes foram eutanasiados com a idade de 53 semanas. Na necroscopia, fragmentos representativos das neoplasias foram colhidos e rotineiramente processados para exame histopatológico. De todos os animais que receberam DMBA, 68,57% desenvolveram algum tipo de tumor. Entre os 70 camundongos tratados com diferentes doses de DMBA, 22 (31,43%) desenvolveram neoplasias mamárias. O adenoacantoma foi o tumor mamário mais comumente diagnosticado (18,75%). Pulmões (15,71%), tecido linfoide (11,43%), estômago (7,14%) e pele (2,86%) foram também locais primários de desenvolvimento de neoplasias. Um terço (33,33%) dos camundongos que receberam 1 mg de DMBA desenvolveram neoplasias pulmonares. Portanto, a administração de DMBA foi considerada um modelo eficiente de carcinogênese em camundongos, especialmente para o estudo de neoplasias mamárias, quando a maior dose é utilizada, e de neoplasias pulmonares, quando utilizada a menor dose. Os modelos de carcinogênese química têm sido usados para diversos estudos na pesquisa em câncer, os resultados aqui apresentados mostram novos fatos para um modelo clássico de carcinogênese.

Study on cow ghee versus soybean oil on 7,12-dimethylbenz(a)-anthracene induced mammary carcinogenesis & expression of cyclooxygenase-2 & peroxisome proliferators activated receptor- γ in rats.

Background & objectives Breast cancer is a leading cause of cancer death in women; dietary fat is the one of the factors that influences its incidence. In the present study we investigated the effect of feeding cow ghee versus soybean oil on 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary cancer in rat and expression of cyclooxygenase-2 and peroxisome proliferators activated receptor- γ (PPAR-γ) in mammary gland. Methods Two groups of 21 day old female rats (30 each) were fed for 44 wk diet containing cow ghee or soybean oil (10%). The animals were given DMBA (30mg/kg body weight) through oral intubation after 5 wk feeding. Another two groups (8 each) fed similarly but not given DMBA served as control for the gene expression study. Results In DMBA treated groups, the animal fed soybean oil had higher tumour incidence (65.4%), tumour weight (6.18 g) and tumour volume (6285 mm3) compared to those fed cow ghee (26.6%, 1.67 g, 1925 mm3, respectively). Tumour latency period was 23 wk on soybean oil compared to 27 wk on cow ghee. Histological analysis of tumours showed that the progression of carcinogenesis was more rapid on soybean oil than on cow ghee. The expression of cyclooxygenase-2 was observed only in DMBA treated rats and it was significantly less on cow ghee than on soybean oil. The expression of PPAR-γ was significantly more on cow ghee than on soybean oil. Interpretation & conclusions Our results show that dietary cow ghee opposed to soybean oil attenuates mammary carcinogenesis induced by DMBA; and the effect is mediated by decreased expression of cyclooxygenase-2 and increased expression of PPAR-γ in the former group.

Evaluation of Tumor Angiogenesis with a Second-Generation US Contrast Medium in a Rat Breast Tumor Model

OBJECTIVE: Tumor angiogenesis is an important factor for tumor growth, treatment response and prognosis. Noninvasive imaging methods for the evaluation of tumor angiogenesis have been studied, but a method for the quantification of tumor angiogenesis has not been established. This study was designed to evaluate tumor angiogenesis in a rat breast tumor model by the use of a contrast-enhanced ultrasound (US) examination with a second-generation US contrast agent. MATERIALS AND METHODS: The alkylating agent 19N-ethyl-N-nitrosourea (ENU) was injected into the intraperitoneal cavity of 30-day-old female Sprague-Dawley rats. Three to four months later, breast tumors were detected along the mammary lines of the rats. A total of 17 breast tumors larger than 1 cm in nine rats were evaluated by gray-scale US, color Doppler US and contrast-enhanced US using SonoVue. The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed. Pathological breast tumor specimens were obtained just after the US examinations. The tumor specimens were stained with hematoxylin and eosin (H & E) and the expression of CD31, an endothelial cell marker, was determined by immunohistochemical staining. We also evaluated the pathological diagnosis of the tumors and the microvessel density (MVD). Spearman's correlation and the Kruskal-Wallis test were used for the analysis. RESULTS: The pathological diagnoses were 11 invasive ductal carcinomas and six benign intraductal epithelial proliferations. The MVD did not correlate with the pathological diagnosis. However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05). CONCLUSION: Contrast-enhanced US using a second-generation US contrast material was useful for the evaluation of tumor angiogenesis of breast tumors in the rat.

Efeitos morfológicos, histológicos e moleculares dos moduladores seletivos dos receptores de estrogênios tamoxifeno e raloxifeno na prevenção primária de tumores mamários quimicamente induzidos em ratas / Morphologic, histological, molecular effects of the SERMs tamoxifen and raloxifene in the primary prevention of chemically induced mammary tumors in rats

O objetivo primário deste trabalho foi avaliar a ação do tamoxifeno (TAM) e do raloxifeno (RAL), na quimioprevenção de tumores mamários quimicamente induzidos em ratas. Foram estudados três grupos (DMBA ou 7,12-Dimetilbenzantraceno, TAM e RAL) compostos de ratas adultas Sprague-Dawley com tumores induzidos quimicamente pelo DMBA. Foi analisada a ação destes SERMs na quimioprevenção mamária, como as características morfológicas e histopatológicas dos tumores induzidos, a porcentagem de receptores de estrogênio e a atividade proliferativa pelo Ki67. A expressão angiogênica em cada grupo foram avaliadas com o método qRT-PCR...

Primary objective was to determine the action of tamoxifen(Tam) and raloxifene(Ral) as chemoprevention agents in chemically induced mammary tumors in rats. Three groups (DMBA or 7,12 dimethybenzanthracen,Tam and Ral) were studied and each group had young female Sprague-Dawley rats received DMBA by gavage. Secondary objectives were to evaluate morphologic and histological aspects ,the percentage of estrogen receptor and proliferative mammary activity(Ki67) and expression of genes involved in modulating the biological process of angiogenesis by qRT-PCR...

A comparative study on the protective effects of 17beta-estradiol, biochanin A and bisphenol A on mammary gland differentiation and tumorigenesis in rats.

Mammary tissue differentiation and tumorigenesis were studied in female rats following subcutaneous injection at 2, 4 and 6 days after birth with low or high doses of 17beta-estradiol (0.1 or 10 microg; E2), biochanin A (0.1 or 10 mg; BCA) or bisphenol A (0.1 or 10.0 mg; BPA). Half of the rats were killed on day 35 to analyze the terminal end bud (TEB), terminal duct (TD) and alveolar bud (AB) of the mammary tissue. The remaining rats were injected, ip, with a dose of 50 mg/kg of N-nitroso-N-methylurea (MNU) at 7 weeks of age and sacrificed 26 weeks later. The incidence and multiplicity of mammary tumors (MT) decreased among all three different treated groups, dose-dependently. However, the pattern of mammary gland differentiation varied. No significant difference was observed after E2 administration. TEB decreased dose-dependently in BCA treated groups and the number of TD and AB were suppressed significantly in BPA high dose group.

Induction of experimental mammary carcinogenesis in rats with 7, 12-dimethylbenz(a)anthracene

OBJETIVO: Testar um modelo experimental de indução química de carcinogênese mamária em ratas. MATERIAL E MÉTODOS: Com 47 dias de vida, 20 ratas Sprague-Dawley, jovens e virgens, receberam por gavagem intragástrica 20 mg de 7,12-dimetilbenz(a)antraceno (DMBA). Oito e 13 semanas depois da injeção de droga as mamas das ratas foram examinadas. Ao final os animais foram sacrificados e fragmentos dos tumores foram estudados ao microscópio. RESULTADO: Oito semanas depois da injeção de DMBA 16 ratas apresentavam tumor nas mamas (80%). Com 13 semanas todas desenvolveram carcinomas de mama (100%), que foram confirmados por análise histopatológica. CONCLUSÃO: Este modelo experimental de indução química de carcinogênese mamária é factível e pode ser empregado em futuras pesquisas para avaliar o papel de substâncias biomoduladoras da tumorigênese.

Chemoprevention of Mammary, Cervix and Nervous system Carcinogenesis in Animals using Cultured Panax ginseng Drugs and Preliminary Clinical Trials in Patients with Precancerous Lesions of the Esophagus and Endometrium

The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.

Factores de crecimiento y oncogenes en adenocarcinomas mamarios inducidos por acetato de medroxyprogesterona en ratones BALB/c / Growth hormones and oncogenes in mammary adenocarcinomas induced by medroxyprogesterone acetate in BALB/c mice

We have studied the involvement of growth factors (GF), their receptors (GF-R) and oncogenes in modulating tumor growth in the medroxyprogesterone acetate (MPA)-induced mammary tumor model in BALB/c mice. We demonstrated the presence of both ligands of the insulin-like growth factor family (IGF-I, IGF-II) and the two types of receptors (IGF-RI, IGF-RII). MPA upregulated IGF-II mRNA and protein levels in hormone-dependent lines (MPA-D). The progression to a hormone-independent phenotype was accompanied by a high constitutive expression of IGF-II and by a significant decrease in IGF-IIR number. An antisense strategy used to evaluate the role of IGF in the MPA-induced growth of epithelial MPA-D cells showed that IGF mediate progestin-induced mammary tumor growth by autocrine/intracrine pathways. We also studied the role of heregulins (HRG), the recently identified ligands for the c-erbB3 and c-erbB4 oncogenes. HRG mRNA expression was restricted to tumors of ductal origin. MPA induced an in vivo up-regulation of HRG expression. Finally, we also found that MPA may be exerting its proliferative effect on MPA-D lines by inhibiting the expression of transforming growth factor beta 1, (TGF-beta 1) and the lack of expression of TGF-beta 1 in hormone-independent tumors may be related to the acquisition of autonomous growth.

Inducción de adenocarcinomas mamarios por progestagenos en ratones BALB/c. Progresión del tumor hormono-dependiente al autónomo / Progestin-induced mammary adenocarcinomas in BALB/c mice. Progression from hormone-dependent to autonomous tumors

We have developed an experimental model in which the administration of progestins induces mammary tumors in female virgin BALB/c mice. In this paper we review the morphological and biological features of progestin-induced tumors, such as estrogen receptor (ER) and progesterone receptor (PR) patterns of expression, hormone dependence and epidermal growth factor receptors (EGF-R) we also examine our data concerning the systemic effects of medroxyprogesterone acetate (MPA) as regards its stimulating EGF synthesis in salivary glands and its subsequent increase in serum. This growth factor seems to play an important role in the induction of mammary tumors. Direct MPA proliferative effects mediated by PR were demonstrated using primary cultures of progestin-dependent (PD) mammary tumors. Antiprogestins inhibited cell growth beyond control values, suggesting that PR are involved in cell proliferation even in the absence of the ligand. Progesterone-independent (PI) tumors expressing high levels of PR and ER are also inhibited by estrogen or antiprogestin treatment, suggesting that PR are involved in the control of autonomous tumor growth. Estrogen-resistant variants may be selected which may revert to an estrogen-sensitive phenotype after several transplants in untreated mice. The similarities between the tumors obtained with this model and human breast cancer as regards morphological features, evolution and the regulation of growth control converts this model into a useful tool to explore the mechanisms related with acquisition of hormone independence and autonomous tumor growth.

Braquiterapia de tumores sólidos: uso del fosfato crómico coloidal / Brachytherapy of solid tumors: use of chromic phosphate coloid

Con el propósito de evaluar la efectividad de una dosis única de [33P]-Fosfato Crómico (Phosphocol(TM)) para el tratamiento de tumores sólidos, se realizaron estudios de bioeliminación, biodistribución y acción terapéutica en ratas portadoreas de tumores experimentales químicamente inducidos. Los resultados demuestran que el porcentaje de eliminación total es de 29.76 + 9.60 por ciento, siendo la eliminación por vía fecal de 23.28 + 8.81 por ciento y la urinaria de 6.48 + 2.11 por ciento. Los estudios de biodistribución revelan que el 51.61 + 5.82 por ciento de la actividad inyectada se encuentra en el tumor, mientras que en órganos donde existen células reticuloendoteliales, se encontró que el porcentaje de actividad es de 13.09 + 5.15 por ciento en hígado y de 2.88 + 1.23 por ciento en pulmón. Por otra parte, los estudios de acción terapéutica demuestran que el porcentaje de regresión tumoral (P.R.T.) es de 61.0 por ciento para los tumores inyectados. Cabe destacar que 4 de los animales tratados mostraron perfiles de bioeliminación, en los cuales, la misma aumentó abruptamente en algún momento del estudio. Estos resultados demuestran que no es recomendable el uso de este tipo de coloides en el tratamiento de tumores sólidos con moderado grado de vascularización, debido a que puede existir movilización del mismo y en consecuencia iradiación de otros órganos no afectados al tratamiento.

Prazosin and stress effect on tumoral growth of 7.12-Dimethylbenz[A]anthracene-induced rat mammary tumors

Repeated isolation stress and prazosin effect were evaluated in 7,12-dimetylbenz [A] anthracene (DMBA) mammary tumors. Tumor volume was significantly lower in stressed than in control animals from 10 to 52 days considering day 1 the moment when tumors became palpable and treament began. Control Prazosin (0.5 mg/Kg) rats showed diminished tumor volume after 40 days. Stress Prazosin curve was similar to stress alone. The proportion of progressing tumors in control was significantly higher than in stressed groups, regardless of Prazosin administration. Body weight gain was similar in every group throughout the experiment. Behavioral studies were performed when stress effect was no longer evident. Grooming and the number of fecal boli were similar in all groups, as well as prolactin serum levels, suggesting that habituation took place. No significant differences were observed between groups for estrogen receptors. However, a greater concentration of progesterone receptors was found in Stressed rats, compared to all other groups. We conclude that the decrease of tumor volume provoked by stress could not be reversed by the alpha 1-adrenergic antagonist prazosin. Then, it appears that the main effect of stress is not mediated by the alpha 1-adrenergic receptors. Higher progesterone receptors in stressed rats could explain the differences observed.

Influencia de la ingestión de grasas y la administración de estradiol en el desarrollo de carcinoma mamario inducido con DMBA en ratas / Influence of the ingestion of grease and the estradiol administration in the grow up in mamary carcinoma induce by DMBA in rats

Datos epidemiológicos sugieren que la dieta rica en grasas es un factor promotor en el desarrollo del cáncer mamario y puede esta relacionado con el estímulo estrogénico. El objetivo del presente estudio es demostrar la acción de la dieta grasa en carcinomas mamarios inducidos con 1,2-dimetilbenza(a)antraceno (DMBA) como agente promotor único o asociado con estímulo estrogénico. Se emplearon tres grupos experimentales: 1) Grupo con dieta grasa (DG) con 20 por ciento de aceite de maíz, 2) grupo con dieta normal (DN), ambos ad libitum; y 3) grupo con dieta subnormal (DSN)(10 g alimento diario). Todos con y sin estímulo estrogénico (1 *g diario de 17ß-estradiol). Al comparar los tres grupos se observó que 19 de los 21 (93 por ciento) animales con DG desarrollaron tumores mamarios, con una aparición temprana (novena semana y con el mayor tamaño (6 cm en promedio)(p=0.009). Los grupos DN Y DSN presentaron comportamiento tumoral menos agresivo, en el primer grupo la prevalencia fue de 61 por ciento con un tamaño tumoral de 5.5 cm; en el segundo la prevalencia fue de 41 por ciento, la latencia mucho mayor (aparición promedio a la semana 17) y tamaño tumoral menor (2 cm). Nuestros resultados indican que la dieta rica en grasas es un factor promotor importante e independiente del estímulo estrogénico. En general la estimulación hormonal no provocó cambios significativos en el comportamiento tumoral, aunque cabe destacar que el grupo DG con estímulo estrogénico presentó la mayor prevalencia en comparación con el resto de los grupos.

Regularización hormonal de los adenocarcinomas mamarios inducidos por acetato de medroxiprogesterona estudios "in vivo" e "in vitro" / Hormonal regulation of the mammary adenocarcinoma induced by medroxiprogesterone acetate: studies \"in vivo\" and \"in vitro\"

En nuestro modelo experimental el acetato de medroxiprogesterona induce adenocarcinomas de mama en hembras vírgenes de la cepa BALB/c. Estos tumores, con receptores para progesterona y estrógenos, originaron líneas de crecimiento hormono-dependientes (HD) o independiente (HI)..La progesterona y el MPA estímulan el crecimiento de las HD y los estrógenos inhiben el crecimiento de las HD y HI. En este trabajo demostramos que cultivos primarios de tumores HD conservan la misma sensibilidad hormonal que los tumores parenterales: la proliferación celular aumenta con concentraciones de MPA 10-9-10-7 M y es inhibida con estrógenos 10-9 o 10-7 M aun en presencia de MPA. Estos resultados sugerirían que las hormonas actúan directamente sobre las células tumorales. En experimentos "in vivo" demostraron que animales tratados con progesterona también desarrollaron adenocarcinomas de mama aunque la incidencia fue menor que en los tratados con MPA. Curiosamente se observó que la mayoría de los adenocarcinomas de mama inducidos por progesterona eran lobulillares y III mientras que en los tratados con MPA la mayoría fue ductal y HD. También se demostró que la ovariectomía y la sialoadenectomía disminuyen el poder carcinogénico del MPA sin alterar el patrón morfológico: 70 por ciento ductal y HD

Potente efeito estrogênico dos esteróides das supra-renais (C19) no crescimento e níveis dos receptores da progesterona em tumores mamários induzidos pelo dimetilbenzeno-antraceno (DMBA) nas ratas / Potent estrogenic effect of adrenal steroids (C19) on growth and levels of progesterone receptors in mammary tumors induced by dimethyl-benzanthracene (DMBA) in rats

Nós estudamos o efeito do tratamento com os esteróides da supra-renais o androstenodiol (delta5-diol) e a dihidroepiandrosterona (DHEA) no crescimento e níveis dos receptores da progesterona em tumores mamários induzidos pelo DMBA nas ratas. Enquanto poucos tumores apareceram nas ratas ooforectomizadas (OOF), (média de 0,60 ñ 0,19/rata) após 24 dias, nas ratas OOF tratadas com delta 5 -diol ou DHEA (2mg, duas vezes por dia), as médias foram 2,54 ñ 0,50 (p < 0,01) e 1,42 ñ 0,26 (p < 0,01) respectivamente. O aparecimento de tumores novos foi muito reduzido nas ratas OOF (0,07 ñ 0,07/rata) durante os 24 dias de observaçäo, com uma média de 0,47 ñ 0,19/rata (p < 0,05) nas ratas intactas. Nas ratas OOF tratadas com delta5-diol ou DHEA o número de tumores novos foram 0,77 ñ 0,26 (p < 0,05) e 0,42 ñ 0,15 (p < 0,05) por animal, respectivamente. Um efeito ainda mais marcante foi observado na área média total dos tumores, os quais decresceram de 4,70 ñ 0,95 cm* nas ratas intactas para 0,75 ñ 0,27 cm* (p < 0,01) após ooforectomia. Valores de 9,79 ñ 2,25 (p < 0,01) e 3,93 ñ 0,86 cm* (p < 0,01) foram encontrados nas ratas OOF tratadas com delta5-diol e DHEA, respectivamente. As ratas OOF tratadas com delta5-diol e DHEA, mostraram um aumento altamente significante (p < 0,01) nos níveis dos receptores da progesterona nos tumores mamários e nos úteros. O peso uterino estava também aumentado (p < 0,01), pelo tratamento com estes dois esteróides das supra-renais. Estes resultados demonstram, pela primeira vez, que os dois esteróides C19 das supra-renais delta5-diol e DHEA, possuem um efeito estimulatório análogo aos dos estrógenos no crescimento e níveis dos receptores da progesterona em tumores mamários induzidos pelo DMBA nas ratas, desta forma comprovando sugestöes do papel importante destes esteróides das supra-renais no câncer de mama e outras patologias estrógeno-sensíveis na espécie humana

Lipídios nutricionais e câncer mamário / Dietary lipids and mammary carcinogenesis

Os lípidios e ácidos graxos dietários interferem na estrutura e funçäo das membranas biológicas, nos níveis hormonais, no sistema imunológico e no reparo do ácido desoxirribonucléico (DNA). Estes efeitos podem estar relacionados com o desenvolvimento da carcinogênese mamária por mecanismos ainda pouco conhecidos. O aumento do consumo diário de lipídios está fortemente associado com o aumento da incidência e da mortalidade por câncer da mama como demonstrado em várias populaçöes humanas

The psychophysiological mediators of stress as it relates to oncology in humans and animals

This study was designed to investigate the effect of stress on cancer development and treatment, and also to determine whether there is any cancer association personality profile. Human studies were supplemented by controlled animal studies. Twenty-nine male and female cancer subjects were studied along with twenty-nine controls. The animal study comprised ninety female Sprague-Dawley rats, which were divided into nine groups of ten. One group was treated with noise stress alone, while another group received no treatment at all. Three groups received the carcinogen 7,12-Dimethylbenz(a)anthracene together with either noise stress, cortisone acetate or 6-mercaptopurine and the rate of tumour growth in these animals was compared to a group that received only the carcinogen, and after tumour growth these animals were subjected to chemotherapy. In addition to the chemotherapy, one of these groups received noise stress and another cortisone acetate. The stress level of the humans and animals was determined by physiological and psychological tests where applicable. The results of the human study revealed that the level of stress among the cancer subjects was higher than among the controls. Even though in some cases cancer development occured after an event that may be considered stressful, it was not easy to conclude whether stress occurred before or after the cancer development. The controlled animal studies revealed, though, that stress alone could not induce tumour development in the observation period of 280 days. Stress, however, influenced tumour growth when the rats were treated with the carcinogen. The findings of this study also suggested that immunosuppression might play a vital role in cancer development. A cancer associated personality profile, depicting among other things a schizophrenic character, was also detected among the human cancer subjects. The treatment of the cancer subjects who had high stress levels was less successful, and this was substantiated by the results of the animal study, which showed that stressed decreased the life span of the animals receiving chemotherapy and stress. The findings of this study suggest that even though stress may not initiate tumour growth, stress influences the growth of potential tumour cells, and may interfere with the response to treatment.