Sensitization of cervix cancer cells to Adriamycin by Pentoxifylline induces an increase in apoptosis and decrease senescence.

BACKGROUND: Chemotherapeutic drugs like Adriamycin (ADR) induces apoptosis or senescence in cancer cells but these cells often develop resistance and generate responses of short duration or complete failure. The methylxantine drug Pentoxifylline (PTX) used routinely in the clinics setting for circulatory diseases has been recently described to have antitumor properties. We evaluated whether pretreatment with PTX modifies apoptosis and senescence induced by ADR in cervix cancer cells. METHODS: HeLa (HPV 18+), SiHa (HPV 16+) cervix cancer cells and non-tumorigenic immortalized HaCaT cells (control) were treated with PTX, ADR or PTX + ADR. The cellular toxicity of PTX and survival fraction were determinated by WST-1 and clonogenic assay respectively. Apoptosis, caspase activation and ADR efflux rate were measured by flow cytometry, senescence by microscopy. IkappaBalpha and DNA fragmentation were determinated by ELISA. Proapoptotic, antiapoptotic and senescence genes, as well as HPV-E6/E7 mRNA expression, were detected by time real RT-PCR. p53 protein levels were assayed by Western blot. RESULTS: PTX is toxic (WST-1), affects survival (clonogenic assay) and induces apoptosis in cervix cancer cells. Additionally, the combination of this drug with ADR diminished the survival fraction and significantly increased apoptosis of HeLa and SiHa cervix cancer cells. Treatments were less effective in HaCaT cells. We found caspase participation in the induction of apoptosis by PTX, ADR or its combination. Surprisingly, in spite of the antitumor activity displayed by PTX, our results indicate that methylxantine, per se does not induce senescence; however it inhibits senescence induced by ADR and at the same time increases apoptosis. PTX elevates IkappaBalpha levels. Such sensitization is achieved through the up-regulation of proapoptotic factors such as caspase and bcl family gene expression. PTX and PTX + ADR also decrease E6 and E7 expression in SiHa cells, but not in HeLa cells. p53 was detected only in SiHa cells treated with ADR. CONCLUSION: PTX is a good inducer of apoptosis but does not induce senescence. Furthermore, PTX reduced the ADR-induced senescence and increased apoptosis in cervix cancer cells.

Culture and Dehydration: A Comparative Study of Caída de la Mollera (Fallen Fontanel) in Three Latino Populations.

A sunken soft-spot or fontanel is a sign for dehydration in infants. Around the world, folk illnesses, such as caída de la mollera in some Latin American cultures, often incorporate this sign as a hallmark of illness, but may or may not incorporate re-hydration therapies in treatment strategies. This report describes a study of lay descriptions of causes, symptoms, and treatments for caída de la mollera in three diverse Latin American populations. A mixed-methods approach was used. Representative community-based samples were interviewed in rural Guatemala, Guadalajara, Mexico, and Edinburgh, Texas, with a 132 item questionnaire on the causes, susceptibility, symptoms, and therapies for caída de la mollera. Cultural consensus analysis was used to estimate community beliefs about caída. Interviews conducted in rural Guatemala (n = 60), urban Mexico (n = 62), and rural Texas on the Mexican border (n = 61) indicated consistency in thematic elements within and among these three diverse communities. The high degree of consistency in the illness explanatory models indicated shared beliefs about caída de la mollera in each of the communities and a core model shared across communities. However, an important aspect of the community beliefs was that rehydration therapies were not widely endorsed. The consistency in explanatory models in such diverse communities, as well as the high degree of recognition and experience with this illness, may facilitate communication between community members, and health care providers/public health intervention planners to increase use of rehydration therapies for caída de la mollera. Recommendations for culturally informed and respectful approaches to clinical communication are provided.

Variation in asthma beliefs and practices among mainland Puerto Ricans, Mexican-Americans, Mexicans, and Guatemalans.

This study reports on community surveys of 160 representative Latino adults in Hartford, CT, Edinburg, TX, Guadalajara, Mexico; and in rural Guatemala. A 142-item questionnaire covered asthma beliefs and practices (e.g., causes, symptoms, and treatments). The cultural consensus model was used to analyze the agreement among respondents within each sample and to describe beliefs. Beliefs were then compared across the four samples. Analysis of the questionnaire data shows that there was overall consistency or consensus regarding beliefs and practices among individuals at each site (intraculturally) and to a lesser extent across respondents of all four different Latino cultural groups (i.e., interculturally). This pattern of response is indicative of a shared belief system among the four groups with regard to asthma. Within this shared belief system though, there is systematic variation between groups in causes, symptoms, and treatments for asthma. The most widely recognized and shared beliefs concerned causes of asthma. Notable differences were present between samples in terms of differences in beliefs about symptoms and treatments. The biomedical model is shown to be a part of the explanatory model at all sites; in addition to the biomedical model, ethnocultural beliefs such as the humoral ("hot/cold") aspects and the importance of balance are also evident. The Connecticut Puerto Ricans had a greater degree of shared beliefs about asthma than did the other three samples (p < 0.00005). It was concluded that the four Latino groups studied share an overall belief system regarding asthma, including many aspects of the biomedical model of asthma. In addition, traditional Latino ethnomedical beliefs are present, especially concerning the importance of balance in health and illness. Many beliefs and practices are site-specific, and caution should be used when using inclusive terms such as "Hispanic" or "Latino," since there is variation as well as commonality among different ethnic groups with regard to health beliefs and practices.