Circulating Tumor DNA in Cancer Management.

Molecular techniques can be very useful in detecting a patient's tumor to guide treatment decisions is increasingly been applied in the care and management of cancer patients. Circulating tumor DNA (ctDNA) containing mutations can be identified in the plasma of cancer patients during the course of the disease. As a non-invasive "liquid biopsies",ctDNA is a potential surrogate for the entire tumor genome. The use of ctDNA might help to determine the disease prognosis,monitor disease progression,monitor the molecular resistance and monitor the tumor heterogeneity. Future developments will need to provide clinical standards to validate the ctDNA as a clinical biomarker and improve the reproducibility and accuracy,in order to be better exploited for personalized medicine.

How the effects of aging and stresses of life are integrated in mortality rates: insights for genetic studies of human health and longevity.

Increasing proportions of elderly individuals in developed countries combined with substantial increases in related medical expenditures make the improvement of the health of the elderly a high priority today. If the process of aging by individuals is a major cause of age related health declines then postponing aging could be an efficient strategy for improving the health of the elderly. Implementing this strategy requires a better understanding of genetic and non-genetic connections among aging, health, and longevity. We review progress and problems in research areas whose development may contribute to analyses of such connections. These include genetic studies of human aging and longevity, the heterogeneity of populations with respect to their susceptibility to disease and death, forces that shape age patterns of human mortality, secular trends in mortality decline, and integrative mortality modeling using longitudinal data. The dynamic involvement of genetic factors in (i) morbidity/mortality risks, (ii) responses to stresses of life, (iii) multi-morbidities of many elderly individuals, (iv) trade-offs for diseases, (v) genetic heterogeneity, and (vi) other relevant aging-related health declines, underscores the need for a comprehensive, integrated approach to analyze the genetic connections for all of the above aspects of aging-related changes. The dynamic relationships among aging, health, and longevity traits would be better understood if one linked several research fields within one conceptual framework that allowed for efficient analyses of available longitudinal data using the wealth of available knowledge about aging, health, and longevity already accumulated in the research field.

Epidemiological evidence that indoor air pollution from cooking with solid fuels accelerates skin aging in Chinese women.

BACKGROUND: Recently, we showed that outdoor air pollution exposure from traffic and industry is associated with an increased risk of skin aging in Caucasian women. In China, indoor air pollution exposure caused by the use of solid fuels like coal is a major health problem and might also increase the risk of skin aging in Chinese women. OBJECTIVE: As cooking with solid fuels is a major source of indoor air pollution exposure in China, we aimed to test if cooking with solid fuels is associated with more pronounced skin aging in Chinese women. METHODS: We conducted two cross-sectional studies in China to assess the association between cooking with solid fuels and signs of skin aging. In Pingding (in northern China) we assessed N=405 and in Taizhou (in southern China) N=857 women between 30 and 90 years of age. Skin aging was evaluated by the SCINEXA score. Indoor air pollution exposure, sun exposure, smoking and other confounders were assessed by questionnaires. Associations were then tested by linear and logistic regression analyses adjusted for further confounders. RESULTS: The analysis showed that cooking with solid fuels was significantly associated with a 5-8% more severe wrinkle appearance on face and an 74% increased risk of having fine wrinkles on back of hands in both studies combined, independent of age and other influences on skin aging. CONCLUSION: The present studies thus corroborate our previous finding that air pollution is associated with skin aging and extend it by showing that indoor air pollution might be another risk factor for skin aging.

Genetics of aging, health, and survival: dynamic regulation of human longevity related traits.

BACKGROUND: The roles of genetic factors in human longevity would be better understood if one can use more efficient methods in genetic analyses and investigate pleiotropic effects of genetic variants on aging and health related traits. DATA AND METHODS: We used EMMAX software with modified correction for population stratification to perform genome wide association studies (GWAS) of female lifespan from the original FHS cohort. The male data from the original FHS cohort and male and female data combined from the offspring FHS cohort were used to confirm findings. We evaluated pleiotropic effects of selected genetic variants as well as gene-smoking interactions on health and aging related traits. Then we reviewed current knowledge on functional properties of genes related to detected variants. RESULTS: The eight SNPs with genome-wide significant variants were negatively associated with lifespan in both males and females. After additional QC, two of these variants were selected for further analyses of their associations with major diseases (cancer and CHD) and physiological aging changes. Gene-smoking interactions contributed to these effects. Genes closest to detected variants appear to be involved in similar biological processes and health disorders, as those found in other studies of aging and longevity e.g., in cancer and neurodegeneration. CONCLUSIONS: The impact of genes on longevity may involve trade-off-like effects on different health traits. Genes that influence lifespan represent various molecular functions but may be involved in similar biological processes and health disorders, which could contribute to genetic heterogeneity of longevity and the lack of replication in genetic association studies.

AlloDerm implants for prevention of Frey syndrome after parotidectomy: a systematic review and meta-analysis.

Although Frey syndrome is not life-threatening, it is identified as the most serious and widely recognized sequela of parotidectomy and has significant potential negative social and psychological implications. Several studies have investigated whether AlloDerm® implants prevent Frey syndrome effectively and safely, however, the conclusions are inconsistent. We aimed to evaluate the precise effectiveness of AlloDerm implants for preventing Frey syndrome after parotidectomy, using a systematic review and meta-analysis. We searched randomized and quis-randomized controlled trials in which AlloDerm implants were compared to blank controls for preventing Frey syndrome after parotidectomy, from the PubMed, Embase, the Cochrane Library and the ISI Web of Knowledge databases, without any language restriction. Two reviewers independently searched, identified, extracted data and assessed methodological quality. Relative risks with 95% confidence intervals were calculated and pooled. Five articles involving 409 patients met the inclusion criteria. Meta-analyses showed a significant 85% relative risk reduction in objective incidence (RR=0.15, 95% CI 0.08-0.30; P<0.00001) and 68% in subjective incidence (RR=0.32, 95% CI 0.19-0.57; P<0.00001) of Frey syndrome with AlloDerm implants; there was a significant 91% relative risk reduction in salivary fistula (RR=0.09, 95% CI 0.01-0.66; P=0.02); there was no statistical significance for the incidence of facial nerve paralysis (RR=0.96, 95% CI 0.84-1.09; P=0.51); there was no statistical significance for the incidence of seroma/sialocele (RR=1.36, 95% CI 0.66-2.80; P=0.40); there was a trend for a small effect in improving facial contour. Adverse events related to AlloDerm implants were not found. There is evidence that AlloDerm reduces the incidence of Frey syndrome effectively and safely, and also has the potential to improve facial contour and decrease salivary fistula. However, it is unclear whether AlloDerm implants improve facial contour and decrease other complications. Thus, further controlled evaluative studies incorporating more precise measures are required.

Deletion of the late cornified envelope genes LCE3C and LCE3B is associated with psoriasis in a Chinese population.

A common deletion comprising LCE3B and LCE3C, members of the late cornified envelope (LCE) gene cluster, has been shown to be significantly associated with psoriasis in several Caucasian populations. The expression of LCE can be induced by skin barrier disruption, leading to psoriatic lesions. To identify whether deletion of genes in the LCE region is a genetic risk factor in the pathogenesis of psoriasis, we genotyped the LCE3C and LCE3B deletion and single-nucleotide polymorphism rs4112788, which is in strong linkage disequilibrium with the LCE gene cluster, via direct sequencing in 468 psoriasis patients and 768 controls in a Chinese population. We found that deletion of the two LCE genes was associated with psoriasis (odds ratio=1.917; 95% confidence interval=1.291-2.847, P=0.001), a conclusion that was similar to that of another independent Chinese cohort study. The deletion was not significantly associated with the age of disease onset, and there was no significant epistatic interaction between deletion and PSORS1 risk allele on 6p21.3. Our study confirms an association between the deletion of LCE3C and LCE3B and psoriasis in a Chinese population.