Improving IL12 immunotherapy in glioblastoma by targeting the long noncoding RNA INCR1.

Purpose: The potent antitumor effects of interleukin 12 (IL12) gene therapy in glioblastoma (GBM) are significantly attenuated by the highly immunosuppressive microenvironment and the upregulation of the PD-1/PD-L1 immune checkpoint. However, combining IL12 gene therapy with PD-1/PD-L1 inhibitors failed to improve efficacy. This study aims to assess the effects of silencing the immunosuppressive long noncoding RNA INCR1 when combined with IL12 therapy.

Significance of Melatonin in the Regulation of Circadian Rhythms and Disease Management.

Melatonin, the 'hormone of darkness' is a neuronal hormone secreted by the pineal gland and other extra pineal sites. Responsible for the circadian rhythm and seasonal behaviour of vertebrates and mammals, melatonin is responsible for regulating various physiological conditions and the maintenance of sleep, body weight and the neuronal activities of the ocular sites. With its unique amphiphilic structure, melatonin can cross the cellular barriers and elucidate its activities in the subcellular components, including mitochondria.

ProGlycProt V3.0: updated insights into prokaryotic glycoproteins and their glycosyltransferases.

ProGlycProt is a comprehensive database of experimentally validated information about protein glycosylation in prokaryotes, including the glycoproteins, glycosyltransferases, and their accessory enzymes. The first release of ProGlycProt featured experimentally validated information on glycoproteins only. For the second release in 2019, the size and scope of the database were expanded twofold, and experimental data on cognate glycosyltransferases and their accessory proteins was incorporated.

Unravelling the reactivity of metastable molybdenum carbide nanoclusters in the C-H bond activation of methane, ethane and ethylene.

C-H bond activation steps in non-oxidative methane dehydroaromatization (MDA), constitute a key functionalization of the reactant and adsorbed species to form aromatics. Previous studies have focused on studying the energetics of these steps at the most stable active sites involving molybdenum carbide species. Herein, a different paradigm is presented via studying the reactivity of a metastable molybdenum carbide (MoC) nanocluster for the C-H bond activation of methane, ethane, and ethylene and comparing it with the reactivity of the lowest energy MoC nanocluster.

Electronic Effect in a Ruthenium Catalyst Designed in Nanoporous N-Functionalized Carbon for Efficient Hydrogenation of Heteroarenes.

Active metal catalysts are the key in chemical industry for sustainable production of multitude of chemical resources. Here, we report a new ruthenium (Ru) composite with a synergistically controlled nanostructure and electronic properties as a highly efficient hydrogenation catalyst which comprises stable small Ru nanoparticles (mean particle size, 0.9 nm) in situ generated into a nanoporous N-functionalized carbon with high surface area ( 650 m g) and has strong electron-donating power of Ru sites of nanoparticles.

Theoretical insights of codoping to modulate electronic structure of and for enhanced photocatalytic efficiency.

and are well known materials in the field of photocatalysis due to their exceptional electronic structure, high chemical stability, non-toxicity and low cost. However, owing to the wide band gap, these can be utilized only in the UV region. Thus, it's necessary to expand their optical response in visible region by reducing their band gap through doping with metals, nonmetals or the combination of different elements, while retaining intact the photocatalytic efficiency.

Oxygen vacancy mediated cubic phase stabilization at room temperature in pure nano-crystalline zirconia films: a combined experimental and first-principles based investigation.

We report here the stabilization of the cubic phase under ambient conditions in the thin films of zirconia synthesized by electron beam evaporation. The cubic phase stabilization was achieved without the use of chemical stabilizers and/or concurrent ion beam bombardment. Films of two different thicknesses (660 nm and 140 nm) were deposited.

Stability of non-metal dopants to tune the photo-absorption of TiO at realistic temperatures and oxygen partial pressures: A hybrid DFT study.

TiO anatase is considered to play a significant importance in energy and environmental research. However, for developing artificial photosynthesis with TiO, the major drawback is its large bandgap of 3.2 eV.

MADD silencing enhances anti-tumor activity of TRAIL in anaplastic thyroid cancer.

ATC is an aggressive disease with limited therapeutic options due to drug resistance. TRAIL is an attractive anti-cancer therapy that can trigger apoptosis in a cancer cell-selective manner. However, TRAIL resistance is a major clinical obstacle for its use as a therapeutic drug.

Loss of MADD expression inhibits cellular growth and metastasis in anaplastic thyroid cancer.

Anaplastic Thyroid Cancer (ATC) is an aggressive malignancy with limited therapeutic options and dismal patient survival. We have previously shown MADD to be differentially overexpressed in multiple cancer histologies and to contribute to tumor cell growth and survival. Therefore, we targeted MADD by gene silencing, explored its effect on cellular proliferation and metastases and examined its therapeutic potential in an orthotopic ATC model in athymic nude mice.

Cancer immunotherapy with check point inhibitor can cause autoimmune adverse events due to loss of Treg homeostasis.

Regulatory T-cells (Tregs) can facilitate immune evasion by tumor cells by dampening anti-tumor immunity. Reduced Teff/Treg ratio and enhanced Treg functional activity have been observed in patients suffering from different types of cancers, and attenuated Treg numbers/functions can serve as prognostic indicators. Normally, Tregs play an essential role in the maintenance of immune tolerance and prevention of autoimmunity.

Molecular aberrations and signaling cascades implicated in the pathogenesis of anaplastic thyroid cancer.

Anaplastic Thyroid Cancer (ATC) accounts for >40% thyroid cancer-related deaths and has a dismal prognosis. In the past decade, significant efforts have been made towards understanding the pathogenesis of this disease and developing novel therapeutics. Unfortunately, effective treatment is still lacking and a more thorough understanding of ATC pathogenesis may provide new opportunities to improve ATC therapeutics.

Restoring self-tolerance in autoimmune diseases by enhancing regulatory T-cells.

Self-tolerance, the state of unresponsiveness to self-tissues/antigens, is maintained through central and peripheral tolerance mechanisms, and a breach of these mechanisms leads to autoimmune diseases. Foxp3 + T-regulatory cells (Tregs) play an essential role in suppressing autoimmune response directed against self-antigens and thereby regulate self-tolerance. Natural Tregs are differentiated in the thymus on the basis of their higher TCR-affinity to self-antigens and migrate to the periphery where they maintain peripheral tolerance.

Therapeutic advances in anaplastic thyroid cancer: a current perspective.

Thyroid cancer incidence is increasing at an alarming rate, almost tripling every decade. In 2017, it was the fifth most common cancer in women. Although the majority of thyroid tumors are curable, about 2-3% of thyroid cancers are refractory to standard treatments.

Critical role of OX40 signaling in the TCR-independent phase of human and murine thymic Treg generation.

Regulatory T cells (Tregs) play a pivotal role in immune-tolerance, and loss of Treg function can lead to the development of autoimmunity. Natural Tregs generated in the thymus substantially contribute to the Treg pool in the periphery, where they suppress self-reactive effector T cells (Teff) responses. Recently, we showed that OX40L (TNFSF4) is able to drive selective proliferation of peripheral Tregs independent of canonical antigen presentation (CAP-independent) in the presence of low-dose IL-2.

Targeting cancer testis antigens for biomarkers and immunotherapy in colorectal cancer: Current status and challenges.

Colorectal cancer ranks third among the estimated cancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor associated molecules to target for biomarker development and immunotherapy.

Sperm associated antigen 9 plays an important role in bladder transitional cell carcinoma.

Background: Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC) which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9) in bladder TCC.

Methodology And Findings: We examined SPAG9 expression and humoral response in 125 bladder TCC patients.

Down regulation of SPAG9 reduces growth and invasive potential of triple-negative breast cancer cells: possible implications in targeted therapy.

Background: Recently, we reported an association of a novel cancer testis (CT) antigen, sperm-associated antigen 9 (SPAG9) expression in breast cancer clinical samples, indicating its potential role in carcinogenesis. Around 15% breast cancers are designated as triple-negative for which treatment modalities are limited. Therefore, in the present study, we assessed the role of SPAG9 in triple-negative breast cancer cells.

The novel cancer-testis antigen A-kinase anchor protein 4 (AKAP4) is a potential target for immunotherapy of ovarian serous carcinoma.

Ovarian cancer is one of the neoplasms affecting the reproductive tract associated with high mortality rate because of limited therapeutic options and an elevated incidence of chemoresistance and recurrence. In this context, immunotherapy may constitute a promising approach to improve survival rates and clinical outcome, raising the need for specific target antigens. Cancer-testis antigens (CTAs) are considered promising candidates in this sense because they are aberrant expressed by various malignancies but not by non-transformed tissue, with the exception of testes.

Expression and humoral response of A-kinase anchor protein 4 in cervical cancer.

Background: Cervical cancer is one of the major gynecologic cancers. In developing countries, because of a lack of medical support and infrastructure, cervical cancer is the leading cause of cancer-related deaths. Therefore, there is a need to identify novel biomarkers for cervical cancers.

A novel cancer testis antigen, A-kinase anchor protein 4 (AKAP4) is a potential biomarker for breast cancer.

Background: Breast cancer is the second leading cause of cancer related deaths in women worldwide. Reports about the early diagnosis of breast cancer are suggestive of an improved clinical outcome and overall survival rate in cancer patients. Therefore, cancer screening biomarker for early detection and diagnosis is urgently required for timely treatment and better cancer management.

Cancer testis antigens: A new paradigm for cancer therapy.

Cancer immunotherapy is a promising field with limited success, also due to lack of tumor-specific targets. In our attempt of exploring novel biomarkers and immunotherapeutic targets against cancer, we have discovered a novel cancer testis antigen, SPAG9, in cancers of different histological origin and demonstrated its potential role in oncogenesis.

Germ cell-specific heat shock protein 70-2 is expressed in cervical carcinoma and is involved in the growth, migration, and invasion of cervical cells.

Background: Cervical cancer is a major cause of death among women worldwide, and the most cases are reported in the least developed countries. Recently, a study on DNA microarray gene expression analysis demonstrated the overexpression of heat shock protein 70-2 (HSP70-2) in cervical carcinoma cells (HeLa). The objective of the current study was to evaluate the association between HSP70-2 expression in cervical carcinogenesis and its potential role in various malignant properties that result in disease progression.