Modulation of replicative senescence of skeletal muscle satellite cells by insulin -like growth factor-I (IGF-I)

Growth and regeneration of postnatal skeletal muscle requires a population of mononuclear myogenic cells, called satellite cells to add/replace myonuclei, which are postmitotic. Wedged between the sarcolemma and the basal lamina of the skeletal muscle fiber, these cells function as the stem cells of mature muscle fibers. Like other normal diploid cells, satellite cells undergo cellular senescence. Investigations of aging in both rodents and humans have shown that satellite cell self-renewal capacity decreases with advanced age. As a consequence, this could be a potential reason for the characteristically observed age-associated loss in skeletal muscle mass (sarcopenia). This provided the rationale that any intervention that can further increase the proliferative capacity of these cells should potentially be able to either delay, or even prevent sarcopenia. ^ Using clonogenicity assays to determine a cell's proliferation potential, these studies have shown that IGF-I enhances the doubling potential of satellite cells from aged rodents. Using a transgenic model, where the mice express the IGF-I transgene specifically in their striated muscles, some of the underlying biochemical mechanisms for the observed increase in replicative life span were delineated. These studies have revealed that IGF-I activates the PI3/Akt pathway to mediate downregulation of p27KIP1, which consequently is associated with an increase in cyclin E-cdk2 kinase activity, phosphorylation of pRb, and upregulation of cyclin A protein. However, the beneficial effects of IGF-I on satellite cell proliferative potential appears to be limited as chronic overexpression of IGF-I in skeletal muscles did not protect against sarcopenia in 18-mo old mice, and was associated with an exhaustion of satellite cell replicative reserves. ^ These results have shown that replicative senescence can be modulated by environmental factors using skeletal muscle satellite cells as a model system. A better understanding of the molecular basis for enhancement of proliferative capacity by IGF-I will provide a rational basis for developing more effective counter-measures against physical frailty. However, the implications of these studies are that these beneficial effects of enhanced proliferative potential by IGF-I may only be over a short-term period, and other alternative approaches may need to be considered. ^

Correlation between dental care utilization and oral cavity cancer in a large sample of community-based United States residents

Cancer of the oral cavity and pharynx remains one of the ten leading causes of cancer death in the United States (US). Besides smoking and alcohol consumption, there are no well established risk factors. While poor dental care had been implicated, it is unknown if the lack of dental care, implying poor dental hygiene predisposes to oral cavity cancer. This study aimed to assess the relationship between dental care utilization during the past twelve months and the prevalence of oral cavity cancer. A cross-sectional design of the National Health Interview Survey of adult, non-institutionalized US residents (n=30,475) was used to assess the association between dental care utilization and self reported diagnosis of oral cavity cancer. Chi square statistic was used to examine the crude association between the predictor variable, dental care utilization and other covariates, while unconditional logistic regression was used to assess the relationship between oral cavity cancer and dental care utilization. There were statistically significant differences between those who utilized dental care during the past twelve months and those who did not with respect to education, income, age, marital status, and gender (p < 0.05), but not health insurance coverage (p = 0.53). Also, those who utilized dental care relative to those who did not were 65% less likely to present with oral cavity cancer, prevalence odds ratio (POR), 0.35, 95% Confidence Interval (CI), 0.12–0.98. Further, higher income advanced age, people of African heritage, and unmarried status were statistically significantly associated with oral cavity cancer, (p < 0.05), but health insurance coverage, alcohol use and smoking were not, p > 0.05. However, after simultaneously controlling for the relevant covariates, the association between dental care and oral cavity cancer did not attenuate nor persist. Thus, compared with those who did not use dental care, those who did wee 62% less likely to present with oral cavity cancer adjusted POR, 0.38, 95% CI, 0.13-1.10. Among US adults residing in community settings, use of dental care during the past twelve months did not significantly reduce the predisposition to oral cavity cancer. However, due to the nature of the data used in this study, which restricts temporal sequence, a large sample prospective study that may identify modifiable factors associated with oral cancer development namely poor dental care, is needed. ^

Response to chemotherapy, recurrence and survival in advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish BRCA mutations, compared to those without

Objectives. Previous studies have shown a survival advantage in ovarian cancer patients with Ashkenazi-Jewish (AJ) BRCA founder mutations, compared to sporadic ovarian cancer patients. The purpose of this study was to determine if this association exists in ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations. In addition, we sought to account for possible "survival bias" by minimizing any lead time that may exist between diagnosis and genetic testing. ^ Methods. Patients with stage III/IV ovarian, fallopian tube, or primary peritoneal cancer and a non-Ashkenazi Jewish BRCA1 or 2 mutation, seen for genetic testing January 1996-July 2007, were identified from genetics and institutional databases. Medical records were reviewed for clinical factors, including response to initial chemotherapy. Patients with sporadic (non-hereditary) ovarian, fallopian tube, or primary peritoneal cancer, without family history of breast or ovarian cancer, were compared to similar cases, matched by age, stage, year of diagnosis, and vital status at time interval to BRCA testing. When possible, 2 sporadic patients were matched to each BRCA patient. An additional group of unmatched, sporadic ovarian, fallopian tube and primary peritoneal cancer patients was included for a separate analysis. Progression-free (PFS) & overall survival (OS) were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazards models were calculated for variables of interest. Matched pairs were treated as clusters. Stratified log rank test was used to calculate survival data for matched pairs using paired event times. Fisher's exact test, chi-square, and univariate logistic regression were also used for analysis. ^ Results. Forty five advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish (non-AJ) BRCA mutations, 86 sporadic-matched and 414 sporadic-unmatched patients were analyzed. Compared to the sporadic-matched and sporadic-unmatched ovarian cancer patients, non-AJ BRCA mutation carriers had longer PFS (17.9 & 13.8 mos. vs. 32.0 mos., HR 1.76 [95% CI 1.13–2.75] & 2.61 [95% CI 1.70–4.00]). In relation to the sporadic- unmatched patients, non-AJ BRCA patients had greater odds of complete response to initial chemotherapy (OR 2.25 [95% CI 1.17–5.41]) and improved OS (37.6 mos. vs. 101.4 mos., HR 2.64 [95% CI 1.49–4.67]). ^ Conclusions. This study demonstrates a significant survival advantage in advanced-stage ovarian cancer patients with non-AJ BRCA mutations, confirming the previous studies in the Jewish population. Our efforts to account for "survival bias," by matching, will continue with collaborative studies. ^

A survey of statural changes with age in the adult population of the United States

A study of the patterns of height loss with age in the Anglo, black, and Mexican-American populations of the United States has been undertaken. The study was based on data gathered by the United States Public Health Service in the Second National Health and Nutrition Examination Survey and the Hispanic Health and Nutrition Examination Survey. Estimates of height loss were obtained by subtracting present stature from a calculated maximum attained height derived from sex- and race/ethnic-specific regression equations relating stature to subischial length. Anglo women have greater height losses than Anglo, black, or Mexican-American males, and black or Mexican-American females. Between 24 and 74 years of age, Anglo women average 3.8 cm. loss in stature. The black populations lose less height than Anglos or Mexican-Americans. Mexican-Americans lose less height than Anglos from 24 to 54 years and then have a greatly increased height loss so that by age 74 their total height loss is the same as Anglos. Standing height, sitting height, body mass index, and the Poverty Index were found to be negatively correlated with height loss. Age was positively correlated to height loss. The most important determinants of the magnitude of height loss with age were sex and ethnicity. ^

Association of processed red meat and prostate cancer stage in Mexican-Americans: A population based case-control study

Objective: The objective of this study is to investigate the association between processed and unprocessed red meat consumption and prostate cancer (PCa) stage in a homogenous Mexican-American population. Methods: This population-based case-control study had a total of 582 participants (287 cases with histologically confirmed adenocarcinoma of the prostate gland and 295 age and ethnicity-matched controls) that were all residing in the Southeast region of Texas from 1998 to 2006. All questionnaire information was collected using a validated data collection instrument. Statistical Analysis: Descriptive analyses included Student's t-test and Pearson's Chi-square tests. Odds ratios and 95% confidence intervals were calculated to quantify the association between nutritional factors and PCa stage. A multivariable model was used for unconditional logistic regression. Results: After adjusting for relevant covariates, those who consume high amounts of processed red meat have a non-significant increased odds of being diagnosed with localized PCa (OR = 1.60 95% CI: 0.85 - 3.03) and total PCa (OR = 1.43 95% CI: 0.81 - 2.52) but not for advanced PCa (OR = 0.91 95% CI: 1.37 - 2.23). Interestingly, high consumption of carbohydrates shows a significant reduction in the odds of being diagnosed with total PCa and advanced PCa (OR = 0.43 95% CI: 0.24 - 0.77; OR = 0.27 95% CI: 0.10 - 0.71, respectively). However, consuming high amounts of energy from protein and fat was shown to increase the odds of being diagnosed with advanced PCa (OR = 4.62 95% CI: 1.69 - 12.59; OR = 2.61 95% CI: 1.04 - 6.58, respectively). Conclusion: Mexican-Americans who consume high amounts of energy from protein and fat had increased odds of being diagnosed with advanced PCa, while high amounts of carbohydrates reduced the odds of being diagnosed with total and advanced PCa.^