Therapeutic Effects of Long-Term Administration of Tranilast in an Animal Model for the Treatment of Fibroids.

Tranilast (N-3, 4-dimethoxycinnamoyl anthranilic acid) is an orally administered drug with antiallergic properties and approved in Japan and the Republic of Korea for the treatment of asthma and hypertrophic scars. Previous in vitro studies indicated that tranilast reduced fibroid growth through its inhibitory effects on cell proliferation and induction of apoptosis. The objective of this study was to determine the efficacy of tranilast for treatment of human-derived fibroids in a mouse model. SCID mice (ovariectomized, supplemented with estrogen and progesterone) were implanted with fibroid explants and treated for two months with tranilast (50 m/kg/daily) or the vehicle. After sacrifice, xenografts were excised and analyzed. Tranilast was well tolerated without adverse side effects. There was a 37% reduction in tumor weight along with a significant decrease in staining for Ki67, CCND1, and E2F1; a significant increase in nuclear staining for cleaved caspase 3; and reduced staining for TGF-ß3 and Masson's trichrome in the tranilast treated mice. There was a significant inhibition of mRNA and protein expression of fibronectin, COL3A1, CCND1, E2F1, and TGF-ß3 in the xenografts from the tranilast-treated mice. These promising therapeutic effects of tranilast warrant additional animal studies and human clinical trials to evaluate its efficacy for treatment of fibroids.

Mechanobiology of Autophagy: The Unexplored Side of Cancer.

Proper execution of cellular function, maintenance of cellular homeostasis and cell survival depend on functional integration of cellular processes and correct orchestration of cellular responses to stresses. Cancer transformation is a common negative consequence of mismanagement of coordinated response by the cell. In this scenario, by maintaining the balance among synthesis, degradation, and recycling of cytosolic components including proteins, lipids, and organelles the process of autophagy plays a central role. Several environmental stresses activate autophagy, among those hypoxia, DNA damage, inflammation, and metabolic challenges such as starvation. In addition to these chemical challenges, there is a requirement for cells to cope with mechanical stresses stemming from their microenvironment. Cells accomplish this task by activating an intrinsic mechanical response mediated by cytoskeleton active processes and through mechanosensitive protein complexes which interface the cells with their mechano-environment. Despite autophagy and cell mechanics being known to play crucial transforming roles during oncogenesis and malignant progression their interplay is largely overlooked. In this review, we highlight the role of physical forces in autophagy regulation and their potential implications in both physiological as well as pathological conditions. By taking a mechanical perspective, we wish to stimulate novel questions to further the investigation of the mechanical requirements of autophagy and appreciate the extent to which mechanical signals affect this process.

[Effectiveness of supervised breast self-examination as educational strategy]. / Efectividad de la autoexploración mamaria supervisada como estrategia educative.

BACKGROUND: Breast cancer is the leading cause of death from cancer in the female population; consequently, there are multiple prevention campaigns. Within these campaigns, a special emphasis is given on promoting monthly breast self-examination; however, many women have never received formal education on proper method of self-examination. OBJECTIVE: To establish if the educational intervention we propose improves the breast self-examination technique. MATERIAL AND METHODS: A descriptive longitudinal study that included 52 women aged 20-40 years, attending a Family Medicine Unit of the Mexican Institute of Social Security, who were evaluated about self-examination technique before and after educational intervention, measured on a scale of 0 to 16. Statistical analysis was made with descriptive statistics and Student's t test. RESULTS: The mean age was 30.76 ± 5.87 years. The mean baseline score was 3.13 ± 2.55. The final average score after a month of the educational intervention was 10.69 ± 2.74, which represents an increase in average score of 7.55 ± 3.53. There was a significant increase in assessment scores after the educational intervention (p < 0.001). CONCLUSIONS: "Supervised breast self-examination" technique showed an increase in the ability of self-examination in patients. It can be considered an effective complementary method of teaching breast self-examination.