Clinical Relevance of Myopenia and Myosteatosis in Colorectal Cancer

Sarcopenia was initially described as a decrease in muscle mass associated with aging and subsequently also as a consequence of underlying disease, including advanced malignancy. Accumulating evidence shows that sarcopenia has clinically significant effects in patients with malignancy, including an increased risk of adverse events associated with medical treatment, postoperative complications, and a poor survival outcome. Colorectal cancer (CRC) is one of the most common cancers worldwide, and several lines of evidence suggest that preoperative sarcopenia negatively impacts various outcomes in patients with CRC. In this review, we summarize the current evidence in this field and the clinical relevance of sarcopenia in patients with CRC from three standpoints, namely, the adverse effects of medical treatment, postoperative infectious complications, and oncological outcomes

Yes-Associated Protein (YAP) Modulates Oncogenic Features and Radiation Sensitivity in Endometrial Cancer

<div><p>Background</p><p>Yes-associated protein (YAP) is a transcriptional co-activator and regulates cell proliferation and apoptosis. We investigated the clinical and biological significance of YAP in endometrial cancer (EMCA).</p><p>Methods</p><p>YAP expression in 150 primary tumor tissues from patients with EMCA was evaluated by immunohistochemistry and its association with clinicopathological data was assessed. The biological functions of YAP were determined in EMCA cell lines through knockdown/overexpression of YAP. The role of YAP in modulating radiation sensitivity was also investigated in EMCA cells.</p><p>Results</p><p>Increased nuclear YAP expression was significantly associated with higher grade, stage, lympho-vascular space invasion, postoperative recurrence/metastasis and overall survival in estrogen mediated EMCA, called type 1 cancer (p = 0.019,  = 0.028,  = 0.0008,  = 0.046 and  = 0.015, respectively). In multivariate analysis, nuclear YAP expression was confirmed as an independent prognostic factor for overall survival in type 1 EMCA. YAP knockdown by siRNA resulted in a significant decrease in cell proliferation (p<0.05), anchorage-dependent growth (p = 0.015) and migration/invasion (p<0.05), and a significant increase in the number of cells in G0/G1 phase (p = 0.002). Conversely, YAP overexpression promoted cell proliferation. Clonogenic assay demonstrated enhanced radiosensitivity by approximately 36% in YAP inhibited cells.</p><p>Conclusions</p><p>Since YAP functions as a transcriptional co-activator, its differential localization in the nucleus of cancer cells and subsequent impact on cell proliferation could have important consequences with respect to its role as an oncogene in EMCA. Nuclear YAP expression could be useful as a prognostic indicator or therapeutic target and predict radiation sensitivity in patients with EMCA.</p></div

Clonogenic assay in HEC-1-B cells after radiation exposure.

<p>Knockdown of YAP expression by siRNA reduced clonogenic survival in HEC-1-B cells, resulting in an increase in radiation sensitivity with a dose enhancement factor at 10% survival (DEF 0.1) of 1.36. Results are shown in means ±standard deviations (bars) in triplicate experiments. Similar trends were obtained in other three independent experiments.</p

Yes-Associated Protein (YAP) Modulates Oncogenic Features and Radiation Sensitivity in Endometrial Cancer - Figure 2

<p>(A) Expression of YAP and phospho-YAP (Ser127) in three EMCA cell lines by western blotting. (B) Immunofluorescent cytochemical staining of endogenous YAP using anti-YAP antibody (YAP: green, DAPI: blue).</p

The Kaplan-Meier curve for overall survival rate of patients with type 1 EMCA (n = 120) according to the nuclear expression of YAP.

<p>Increased nuclear immunoreactivity of YAP was significantly associated with worse overall survival (P = 0.015, log-rank test).</p

Comparison of demographic data and YAP expression between type 1 and type 2 EMCA.

<p>BMI; Body mass index, LVSI; Lymphovascular space involvement, N.S.; not significant.</p><p>(a): Student's t-test, (b): Chi square test (there is no <10 number in data)/Fisher's exact test (there is <10 number in data).</p

Circulating MicroRNAs: A Next-Generation Clinical Biomarker for Digestive System Cancers

MicroRNAs (miRNAs) are short noncoding RNAs that post-transcriptionally regulate gene expression and play important roles in various physiological and developmental processes such as oncogenic or tumor suppressive regulators. Specific miRNA expression signatures have been identified in a number of human cancers. Cell-free miRNAs have recently been stably detected in plasma and serum (circulating miRNAs), and their presence in blood has attracted the attention of researchers due to their potential as non-invasive biomarkers. Circulating miRNAs have emerged as tumor-associated biomarkers that reflect not only the existence of early-stage tumors, but also the dynamics and status of advanced stage tumors, tumor recurrence, and drug sensitivities. This methodology for liquid biopsy may provide non-invasive and reproductive biomarkers and individualized therapeutic strategies for cancer patients. We herein review the current phase of biological and clinical research on the circulating miRNAs of solid cancers, particularly digestive tract cancers, and discuss future perspectives. The present review may be beneficial for future research on miRNAs used to detect various cancers