Antonieta Alvarado

HPV16 induces a wasting syndrome in transgenic mice: Amelioration by dietary polyphenols via NF-κB inhibition

&NA; Cancer patients often show a wasting syndrome for which there are little therapeutic options. Dietary polyphenols have been proposed for treating this syndrome, but their usefulness in cases associated with human papillomavirus (HPV)‐induced cancers is unknown. We characterized HPV16‐transgenic mice as a model of cancer cachexia and tested the efficacy of long‐term oral supplementation with polyphenols curcumin and rutin. Both compounds were orally administered to six weeks‐old HPV16‐transgenic mice showing characteristic multi‐step skin carcinogenesis, for 24 weeks. Skin lesions and blood, liver and spleen inflammatory changes were characterized histologically and hematologically. Hepatic oxidative stress, skeletal muscle mass and the levels of muscle pro‐inflammatory transcription factor NF‐&kgr;B were also assessed. Skin carcinogenesis was associated with progressive, severe, systemic inflammation (leukocytosis, hepatitis, splenitis), significant mortality and cachexia. Curcumin and rutin totally suppressed mortality while reducing white blood cells and the incidence of splenitis and hepatitis. Rutin prevented muscle wasting more effectively than curcumin. Preservation of muscle mass and reduced hepatic inflammation were associated with down‐regulation of the NF‐&kgr;B canonical pathway and with reduced oxidative stress, respectively. These results point out HPV16‐transgenic mice as a useful model for studying the wasting syndrome associated with HPV‐induced cancers. Dietary NF‐&kgr;B inhibitors may be useful resources for treating this syndrome.

Experimental mammary carcinogenesis - Rat models

&NA; Mammary cancer is one of the most common cancers, victimizing more than half a million of women worldwide every year. Despite all the studies in this field, the current therapeutic approaches are not effective and have several devastating effects for patients. In this way, the need to better understand the mammary cancer biopathology and find effective therapies led to the development of several rodent models over years. With this review, the authors intended to provide the readers with an overview of the rat models used to study mammary carcinogenesis, with a special emphasis on chemically‐induced models. Graphical abstract Figure. No caption available.

A spontaneous high-grade undifferentiated mammary carcinoma in a seven-week-old female rat

The present work describes a rare case of a spontaneous high-grade carcinoma in a seven-week-old Sprague-Dawley female rat that had been included in the control group of an assay of mammary carcinogenesis. The mass was detected at 50days of age, it grown quickly and the animal was humanely sacrificed eight days later. The tumor was located in the left cervical region, in the vicinity of the left submandibular and sublingual glands. It was soft and reddish and had several dens with a bloody content. The tumor was PAS negative and exhibited immunostaining for ER-α. The histopathologic and immunohistochemical data are suggestive of a high-grade carcinoma from mammary gland. It was the first report of a spontaneous mammary tumor in such a young rat.

Effects of exercise training on breast cancer metastasis in a rat model

Exercise training is thought to play a protective role against cancer development and metastasis, either by reducing hormonal stimulation of hormone‐dependent cancers or by reducing the permeability of vascular walls towards invading metastatic cells. The purpose of this work was to evaluate the role of long‐term exercise training in the development and metastasis of breast cancer, in an immune‐competent 1‐methyl‐1‐nitrosourea (MNU) induced rat model. A single MNU dose was administered to Sprague‐Dawley rats at 50 days of age and the rats were subjected to exercise training on a treadmill at 20 m/min, 60 min/day, 5 days/week for 35 weeks. Exercised animals developed slightly less (2.30 ± 1.42) tumours per animal than sedentary animals (2.55 ± 1.44) and did not develop any metastasis, while two pulmonary metastases were observed in the sedentary group. All primary neoplasms and their metastases were positive for oestrogen (ER) α and progesterone (PR) receptors, indicating high hormonal sensitivity. Interestingly, exercise training increased circulating oestrogen levels, thus suggesting that the mechanism might involve either or both of a protective hormone‐independent effect and modulation of tumoural vascularization.