Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2α contributes to human bladder cancer cell survival

<p>Abstract</p> <p>Background</p> <p>Survival rate for patients presenting muscle invasive bladder cancer is very low, and useful therapeutic target has not been identified yet. In the present study, new COX2 downstream signals involved in urothelial carcinoma cell survival were investigated <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>COX2 gene was silenced by siRNA transfection. Orthotopic implantation animal model and transurethral instillation of siRNA with atelocollagen was constructed to examine the effects of COX2 knockdown <it>in vivo</it>. Cell cycle was examined by flowcytoketry. Surgical specimens derived from patients with urinary bladder cancer (all were initially diagnosed cases) were used for immunohistochemical analysis of the indicated protein expression in urothelial carcinoma cells.</p> <p>Results</p> <p>Treatment with the COX2 inhibitor or knockdown of COX2 reduced expression of casein kinase (CK) 2 α, a phophorylated Akt and urokinase type plasminogen activator (uPA), resulting in p27 induction, cell cycle arrest at G1 phase and cell growth suppression in human urothelial carcinoma cell lines expressing COX2. Silencing of CK2α exhibited the similar effects. Even in UMUC3 cells lacking the COX2 gene, COX2 inhibition also inhibited cell growth through down-regulation of the CK2α-Akt/uPA axis. The mouse orthotropic bladder cancer model demonstrated that the COX2 inhibitor, meloxicam significantly reduced CK2α, phosphorylated Akt and uPA expression, whereas induced p27 by which growth and invasiveness of bladder cancer cells were strongly inhibited. Immunohistochemically, high expression of COX2, CK2α and phosphorylated form of Akt was found in high-grade, invasive carcinomas as well as carcinoma <it>in situ</it>, but not in low-grade and noninvasive phenotypes.</p> <p>Conclusions</p> <p>COX2-dependent and independent activation of CK2α-Akt/uPA signal is mainly involved in urothelial carcinoma cell survival, moreover, not only COX2 but also CK2α could be direct targets of COX2 inhibitors.</p

Derivation of a Triple Mosaic Adenovirus for Cancer Gene Therapy

A safe and efficacious cancer medicine is necessary due to the increasing population of cancer patients whose particular diseases cannot be cured by the currently available treatment. Adenoviral (Ad) vectors represent a promising therapeutic medicine for human cancer therapy. However, several improvements are needed in order for Ad vectors to be effective cancer therapeutics, which include, but are not limited to, improvement of cellular uptake, enhanced cancer cell killing activity, and the capability of vector visualization and tracking once injected into the patients. To this end, we attempted to develop an Ad as a multifunctional platform incorporating targeting, imaging, and therapeutic motifs. In this study, we explored the utility of this proposed platform by generating an Ad vector containing the poly-lysine (pK), the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK), and the monomeric red fluorescent protein (mRFP1) as targeting, tumor cell killing, and imaging motifs, respectively. Our study herein demonstrates the generation of the triple mosaic Ad vector with pK, HSV-1 TK, and mRFP1 at the carboxyl termini of Ad minor capsid protein IX (pIX). In addition, the functionalities of pK, HSV-1 TK, and mRFP1 proteins on the Ad vector were retained as confirmed by corresponding functional assays, indicating the potential multifunctional application of this new Ad vector for cancer gene therapy. The validation of the triple mosaic Ad vectors also argues for the ability of pIX modification as a base for the development of multifunctional Ad vectors

Estimating the Global Clinical Burden of Plasmodium falciparum Malaria in 2007

Simon Hay and colleagues derive contemporary estimates of the global clinical burden of Plasmodium falciparum malaria (the deadliest form of malaria) using cartography-based techniques

Water Extract from the Leaves of Withania somnifera Protect RA Differentiated C6 and IMR-32 Cells against Glutamate-Induced Excitotoxicity

Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative disorders. Search for herbal remedies that may possibly act as therapeutic agents is an active area of research to combat these diseases. The present study was designed to investigate the neuroprotective role of Withania somnifera (Ashwagandha), also known as Indian ginseng, against glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6) and human neuroblastoma (IMR-32) cells. The neuroprotective activity of the Ashwagandha leaves derived water extract (ASH-WEX) was evaluated. Cell viability and the expression of glial and neuronal cell differentiation markers was examined in glutamate challenged differentiated cells with and without the presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule) and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty

Vitamin D deficiency, skin, and sunshine: A review

The sunshine vitamin - “Vitamin D” is a subject of interest that attracted researcher’s attention in the past few decades. Vitamin D is a fat-soluble vitamin and also a nutrient which increases the calcium absorption and plays an important part in the maintenance of body’s immune system and bone formation. However, the deficiency of Vitamin D, also known as hypovitaminosis D, will affect various body parts such as the brain, heart, muscle, immune system, and bones. Thus, the deficiency leads to severe conditions such as osteopenia, osteoporosis, rickets (in children), hypertension, fractures and falls in adults, cancers, diabetes, autoimmune diseases, infections, and neurological disorders. An effective approach for the deficiency prevention is the thorough understanding of Vitamin D sources, Vitamin D serum levels, and deficiency symptoms, linked with different pathological conditions, requirement and maintenance in the body, sunlight exposure duration, and effective treatment dose. Therefore, the present review will lay an emphasis on the role of Vitamin D, the reasons for its deficiency, available sources, and treatment options reported so far

Oxygen plasma assisted end-opening and field emission enhancement in vertically aligned multiwall carbon nanotubes

This paper highlights the changes in micro-structural and field emission properties of vertically aligned carbon nanotubes (VACNTs) via oxygen plasma treatment. We find that exposure of very low power oxygen plasma (6 W) at 13.56 MHz for 15-20 min, opens the tip of vertically aligned CNTs. Scanning electron microscopy and transmission electron microscopy images were used to identify the quality and microstructural changes of the nanotube morphology and surfaces. Raman spectra showed that the numbers of defects were increased throughout the oxygen plasma treatment process. In addition, the hydrophobic nature of the VACNTs is altered significantly and the contact angle decreases drastically from 110 degrees to 40 degrees. It was observed that the electron field emission (EFE) characteristics are significantly enhanced. The turn-on electric field (ETOE) of CNTs decreased from similar to 0.80 V mu m(-1) (untreated) to similar to 0.60 V mu m(-1) (oxygen treated). We believe that the open ended VACNTs would be immensely valuable for applications such as micro/nanofluidic based filtering elements and display devices. (C) 2012 Elsevier B.V. All rights reserved

Treatment strategies against diabetes: Success so far and challenges ahead

© 2019 Elsevier B.V. The growing disease burden of diabetes mellitus is an important public health concern, affecting over 400 million people globally. This epidemic, if not controlled in time, leads to life threatening complications, compromise in quality of life, and eventually mortality. Over time, many attempts have been made for the effective treatment of diabetes but true success has never been achieved. Pharmacological and non-pharmacological approaches for the treatment of hyperglycaemia have been ever-evolving due to limitations of current therapies. Non pharmacological management which includes diet management and exercise, has been the primary focus for self-management of diabetes. The pharmacological management includes oral antihyperglycaemics, phytoconstituents, and combination products. Advancements such as nanocarrier delivery systems have been made in drug delivery to overcome the challenges such as poor bioavailability associated with conventional dosage forms currently employed in diabetes treatment. In recent years, much emphasis has been given to synbiotics that act on gut microbiota, as an emerging therapy for diabetes. The current review discusses different treatment strategies for diabetes management starting from insulin therapy to synbiotics. The combination of herbal phytoconstituents with synthetic drugs, synthetic drug combinations, novel drug delivery systems for insulin are highlighted. Moreover, the role of gut dysbiosis in diabetes and its treatment by administration of synbiotics in various clinical as well as non clinical studies has been discussed in detail