Effects of an integrated yoga program in modulating perceived stress levels, anxiety, as well as depression levels and radiation-induced DNA damage were studied in 68 breast cancer patients undergoing radiotherapy. Two psychological questionnaires-Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS)-and DNA damage assay were used in the study. There was a significant decrease in the HADS scores in the yoga intervention group, whereas the control group displayed an increase in these scores. Mean PSS was decreased in the yoga group, whereas the control group did not show any change pre-and postradiotherapy. Radiation-induced DNA damage was significantly elevated in both the yoga and control groups after radiotherapy, but the postradiotherapy DNA damage in the yoga group was slightly less when compared to the control group. An integrated approach of yoga intervention modulates the stress and DNA damage levels in breast cancer patients during radiotherapy.

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Background: Cause of the complete loss of CDC73 in a subset of parathyroid tumors remains to be elucidated in the absence of a second mutation and promoter methylation. Results: Oncogenic miR-155 causes down-regulation of tumor suppressor CDC73 in OSCC. Conclusion: miR-155 up-regulation adds yet another mechanism for CDC73 down-regulation in tumors. Significance: Targeting miR-155 adds novelty to OSCC therapeutics.

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Metastable phenotypic state transitions in cancer cells can lead to the development of transient adaptive resistance or tolerance to chemotherapy. Here, we report that the acquisition of a phenotype marked by increased abundance of CD44 (CD44Hi) by breast cancer cells as a tolerance response to routinely used cytotoxic drugs, such as taxanes, activated a metabolic switch that conferred tolerance against unrelated standard-of-care chemotherapeutic agents, such as anthracyclines. We characterized the sequence of molecular events that connected the induced CD44Hi phenotype to increased activity of both the glycolytic and oxidative pathways and glucose flux through the pentose phosphate pathway (PPP). When given in a specific order, a combination of taxanes, anthracyclines, and inhibitors of glucose-6-phosphate dehydrogenase (G6PD), an enzyme involved in glucose metabolism, improved survival in mouse models of breast cancer. The same sequence of the three-drug combination reduced the viability of patient breast tumor samples in an explant system. Our findings highlight a convergence between phenotypic and metabolic state transitions that confers a survival advantage to cancer cells against clinically used drug combinations. Pharmacologically targeting this convergence could overcome cross-drug tolerance and could emerge as a new paradigm in the treatment of cancer.

Background: ESRRA is frequently up-regulated in several cancers. However, the mechanism underlying its up-regulation remains elusive. Results: Down-regulation of tumor suppressor miR-125a causes up-regulation of ESRRA in OSCC. Conclusion: Down-regulation of miR-125a is a novel mechanism for up-regulation of ESRRA in OSCC. Significance: Targeting miR-125a via a synthetic mimic adds novelty to OSCC therapeutics.

Mutations in the MCPH1 (microcephalin 1) gene, located at chromosome 8p23.1, result in two autosomal recessive disorders: primary microcephaly and premature chromosome condensation syndrome. MCPH1 has also been shown to be downregulated in breast, prostate and ovarian cancers, and mutated in 1/10 breast and 5/41 endometrial tumors, suggesting that it could also function as a tumor suppressor (TS) gene. To test the possibility of MCPH1 as a TS gene, we first performed LOH study in a panel of 81 matched normal oral tissues and oral squamous cell carcinoma (OSCC) samples, and observed that 14/71 (19.72%) informative samples showed LOH, a hallmark of TS genes. Three protein truncating mutations were identified in 1/15 OSCC samples and 2/5 cancer cell lines. MCPH1 was downregulated at both the transcript and protein levels in 21/41 (51.22%) and 19/25 (76%) OSCC samples respectively. A low level of MCPH1 promoter methylation was also observed in 4/40 (10%) tumor samples. We further observed that overexpression of MCPH1 decreased cellular proliferation, anchorage-independent growth in soft agar, cell invasion and tumor size in nude mice, indicating its tumor suppressive function. Using bioinformatic approaches and luciferase assay, we showed that the 3′-UTR of MCPH1 harbors two non-overlapping functional seed regions for miR-27a which negatively regulated its level. The expression level of miR-27a negatively correlated with the MCPH1 protein level in OSCC. Our study indicates for the first time that, in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is regulated by miR-27a.