Yoga as an ancillary treatment for neurological and psychiatric disorders: a review.

Yoga is gaining acceptance as an ancillary medical treatment, but there have been few studies evaluating its therapeutic benefits in neurological and major psychiatric conditions. The authors reviewed the literature in English on the efficacy of yoga for these disorders. Only randomized, controlled trials were included, with the exception of the only study of yoga for bipolar disorder, which was observational. Trials were excluded if yoga was not the central component of the intervention. Of seven randomized, controlled trials of yoga in patients with neurological disorders, six found significant, positive effects. Of 13 randomized, controlled trials of yoga in patients with psychiatric disorders, 10 found significant, positive effects. These results, although encouraging, indicate that additional randomized, controlled studies are needed to critically define the benefits of yoga for both neurological and psychiatric disorders.

Chemosensitization and immunosensitization of resistant cancer cells to apoptosis and inhibition of metastasis by the specific NF-kappaB inhibitor DHMEQ.

Tumors develop resistance to cytotoxic apoptotic stimuli induced by various chemotherapeutic drugs and immunotherapies. Therefore, there is a need to overcome chemo- and immuno-resistance of tumors through the development of small molecules, as sensitizing agents, aimed at targeting gene products that regulate the apoptotic pathways and allow therapeutics to be effective. The constitutively activated NF-kappaB (nuclear factor kappa B) signaling pathway is involved in cell survival, inflammation and metastasis and is invariably constitutively activated in most cancers. Consequently, NF-kappaB is intimately involved in the regulation of resistance to cytotoxic drugs. A novel NF-kappaB inhibitor, DHMEQ (dehydroxymethylepoxyquinomicin), inhibits the translocation of NF-kappaB into the nucleus as well as inhibits DNA binding of NF-kappaB components and was shown to be a potent chemo- and immuno-sensitizing agent and in combination with cytotoxic therapeutics resulted in significant reversal of resistance and tumor cell death. This review will present various lines of evidence supporting the therapeutic efficacy of DHMEQ when used in combination with conventional/new cytotoxic drugs in the treatment of resistant tumor cells as well as in the prevention of metastasis.

Regulation of tumor cell sensitivity to TRAIL-induced apoptosis by the metastatic suppressor Raf kinase inhibitor protein via Yin Yang 1 inhibition and death receptor 5 up-regulation.

Raf-1 kinase inhibitor protein (RKIP) has been implicated in the regulation of cell survival pathways and metastases, and is poorly expressed in tumors. We have reported that the NF-kappaB pathway regulates tumor resistance to apoptosis by the TNF-alpha family via inactivation of the transcription repressor Yin Yang 1 (YY1). We hypothesized that RKIP overexpression may regulate tumor sensitivity to death ligands via inhibition of YY1 and up-regulation of death receptors (DRs). The TRAIL-resistant prostate carcinoma PC-3 and melanoma M202 cell lines were examined. Transfection with CMV-RKIP, but not with control CMV-EV, sensitized the cells to TRAIL-mediated apoptosis. Treatment with RKIP small interfering RNA (siRNA) inhibited TRAIL-induced apoptosis. RKIP overexpression was paralleled with up-regulation of DR5 transcription and expression; no change in DR4, decoy receptor 1, and decoy receptor 2 expression; and inhibition of YY1 transcription and expression. Inhibition of YY1 by YY1 siRNA sensitized the cells to TRAIL apoptosis concomitantly with DR5 up-regulation. RKIP overexpression inhibited several antiapoptotic gene products such as X-linked inhibitor of apoptosis (XIAP), c-FLIP long, and Bcl-x(L) that were accompanied with mitochondrial membrane depolarization. RKIP overexpression in combination with TRAIL resulted in the potentiation of these above effects and activation of caspases 8, 9, and 3, resulting in apoptosis. These findings demonstrate that RKIP overexpression regulates tumor cell sensitivity to TRAIL via inhibition of YY1, up-regulation of DR5, and modulation of apoptotic pathways. We suggest that RKIP may serve as an immune surveillance cancer gene, and its low expression or absence in tumors allows the tumor to escape host immune cytotoxic effector cells.

Reversal of resistance to cytotoxic cancer therapies: DHMEQ as a chemo-sensitizing and immuno-sensitizing agent.

The development of tumor cell resistance to conventional therapeutics is a major clinical problem. There is an urgent need to develop novel therapeutics to overcome resistance and save patients from tumor recurrences. Novel therapeutics are currently being developed based on better understanding of the underlying molecular mechanisms that govern resistance and the identification of targets that control resistance. One of the major factors that controls resistance is the transcription factor nuclear factor kappaB (NF-kappaB) that has been shown to be constitutively activated in the majority of cancers and is responsible, in large part, for tumor cell survival, growth and direct activation of anti-apoptotic gene products. The development of non-toxic inhibitors of NF-kappaB activity may result in diminishing the anti-apoptotic threshold of resistant tumor cells and leading to inhibition of tumor cell growth and cell death or sensitization to the apoptotic effects of cytotoxic therapeutics. The novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), selectively prevents the translocation of NF-kappaB into the nucleus and, hence, prevents its various transcriptional functions. Thus, DHMEQ is unlike many other NF-kappaB inhibitors that target gene products of the NF-kappaB pathway and it is also unlike proteasome inhibitors that prevent the degradation of pIkappaB. DHMEQ is a small molecule shown to be non-toxic in mice and rodents and exerts direct anti-tumor effects in vitro and in vivo as well as significant chemo- and immuno-sensitizing activities in resistant tumor cells. The present review summarizes studies that have used DHMEQ as a novel anti-cancer agent.