Impact of B7-H3 expression on metastasis, immune exhaustion and JAK/STAT and PI3K/AKT pathways in clear cell renal cell carcinoma.

Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors (TKIs) are improving the response rates of advanced renal cancer patients. However, many treated patients do not respond, making novel immune checkpoint-based immunotherapies potentially clinically beneficial only for specific groups of patients. We detected high expression of the immune checkpoint protein B7-H3 in clear cell renal cell carcinomas (ccRCCs) and evaluated B7-H3 immunohistochemistry staining in tissue microarray samples from two distinct renal cancer cohorts.

A functional role for glycosylated B7-H5/VISTA immune checkpoint protein in metastatic clear cell renal cell carcinoma.

Increased expression of the B7 family of immune checkpoint proteins hinders tumor elimination by the immune system. Expression levels of the B7-H5 protein were found to be upregulated in clear cell renal cell carcinomas (ccRCC). We here report the molecular, functional, and clinical characterization of B7-H5 from renal cancer cells and metastatic ccRCC tumors.

Potentiation by Protein Synthesis Inducers of Translational Readthrough of Pathogenic Premature Termination Codons in PTEN Isoforms.

The PTEN tumor suppressor is frequently targeted in tumors and patients with PTEN hamartoma tumor syndrome (PHTS) through nonsense mutations generating premature termination codons (PTC) that may cause the translation of truncated non-functional PTEN proteins. We have previously described a global analysis of the readthrough reconstitution of the protein translation and function of the human canonical PTEN isoform by aminoglycosides. Here, we report the efficient functional readthrough reconstitution of the PTEN translational isoform PTEN-L, which displays a minimal number of PTC in its specific N-terminal extension in association with disease.

Predicting Survival of Metastatic Clear Cell Renal Cell Cancer Treated with VEGFR-TKI-Based Sequential Therapy.

(1) Objective: To develop a clinically useful nomogram that may provide a more individualized and accurate estimation of cancer-specific survival (CSS) for patients with clear-cell (CC) metastatic renal cell carcinoma (mRCC) treated with nephrectomy and vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI)-based sequential therapy. (2) Methods: A prospectively maintained database of 145 patients with mRCC treated between 2008 and 2018 was analyzed to predict the CSS of patients receiving sunitinib and second- and third-line therapies according to current standards of practice. A nomogram based on four independent clinical predictors (Eastern Cooperative Oncology Group status, International Metastatic RCC Database Consortium score, the Morphology, Attenuation, Size and Structure criteria and Response Evaluation Criteria in Solid Tumors response criteria) was calculated.

B7-H3: a robust target for immunotherapy in prostate cancer.

B7-H3, an immune checkpoint glycoprotein, facilitates immune evasion and the promotion of tumors and is highly expressed on the surface of prostate cancer (PCa) cells, which makes it a feasible and robust candidate for immunotherapies against advanced prostate cancer. Here, we summarize and discuss recent findings on the suitability of targeting B7-H3 in PCa treatment.

The lincRNA JUNI regulates the stress-dependent induction of c-Jun, cellular migration and survival through the modulation of the DUSP14-JNK axis.

Cancer cells employ adaptive mechanisms to survive various stressors, including genotoxic drugs. Understanding the factors promoting survival is crucial for developing effective treatments. In this study, we unveil a previously unexplored long non-coding RNA, JUNI (JUN-DT, LINC01135), which is upregulated by genotoxic drugs through the activation of stress-activated MAPKs, JNK, and p38 and consequently exerts positive control over the expression of its adjacent gene product c-Jun, a well-known oncoprotein, which transduces signals to multiple transcriptional outputs.

Induction of Translational Readthrough on Protein Tyrosine Phosphatases Targeted by Premature Termination Codon Mutations in Human Disease.

Nonsense mutations generating premature termination codons (PTCs) in various genes are frequently associated with somatic cancer and hereditary human diseases since PTCs commonly generate truncated proteins with defective or altered function. Induced translational readthrough during protein biosynthesis facilitates the incorporation of an amino acid at the position of a PTC, allowing the synthesis of a complete protein. This may evade the pathological effect of the PTC mutation and provide new therapeutic opportunities.

First-Principles Calculations of Magnetite (FeO) above the Verwey Temperature by Using Self-Consistent DFT + + .

In this report, we have used the DFT + + approach, an extension of the DFT + approach that takes into account both on-site and intersite interactions, to simulate structural, magnetic, and electronic properties together with the Fe and O K-edge XAS spectra of FeO above the Verwey temperature (). Moreover, we compared the simulated XAS spectra with experimental XAS data. We examined both orthogonalized and nonorthogonalized atomic orbital projectors and compared DFT + + to DFT, DFT + , and HSE as a hybrid functional.

Functionalization of breast implants by cyclodextrin polymerization: a local drug delivery system for augmentation mammaplasty.

Mammaplasty is a widely performed surgical procedure worldwide, utilized for breast reconstruction, in the context of breast cancer treatment, and aesthetic purposes. To enhance post-operative outcomes and reduce risks (hematoma with required evacuation, capsular contracture, implant-associated infection and others), the controlled release of medicaments can be achieved using drug delivery systems based on cyclodextrins (CDs). In this study, our objective was to functionalize commercially available silicone breast implants with smooth and textured surfaces through polymerization of two CDs: β-CD/citric acid and 2-hydroxypropyl-β-CD/citric acid.

Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants.

PTEN is a major tumor suppressor gene frequently mutated in human tumors, and germline PTEN gene mutations are the molecular diagnostic of PTEN Hamartoma Tumor Syndrome (PHTS), a heterogeneous disorder that manifests with multiple hamartomas, cancer predisposition, and neurodevelopmental alterations. A diversity of translational and splicing PTEN isoforms exist, as well as PTEN C-terminal truncated variants generated by disease-associated nonsense mutations. However, most of the available anti-PTEN monoclonal antibodies (mAb) recognize epitopes at the PTEN C-terminal tail, which may introduce a bias in the analysis of the expression of PTEN isoforms and variants.

Antibacterial Films of Silver Nanoparticles Embedded into Carboxymethylcellulose/Chitosan Multilayers on Nanoporous Silicon: A Layer-by-Layer Assembly Approach Comparing Dip and Spin Coating.

The design and engineering of antibacterial materials are key for preventing bacterial adherence and proliferation in biomedical and household instruments. Silver nanoparticles (AgNPs) and chitosan (CHI) are broad-spectrum antibacterial materials with different properties whose combined application is currently under optimization. This study proposes the formation of antibacterial films with AgNPs embedded in carboxymethylcellulose/chitosan multilayers by the layer-by-layer (LbL) method.

The expression pattern of pyruvate dehydrogenase kinases predicts prognosis and correlates with immune exhaustion in clear cell renal cell carcinoma.

Renal cancer cells constitute a paradigm of tumor cells with a glycolytic reprogramming which drives metabolic alterations favouring cell survival and transformation. We studied the expression and activity of pyruvate dehydrogenase kinases (PDK1-4), key enzymes of the energy metabolism, in renal cancer cells. We analysed the expression, subcellular distribution and clinicopathological correlations of PDK1-4 by immunohistochemistry of tumor tissue microarray samples from a cohort of 96 clear cell renal cell carcinoma (ccRCC) patients.

First-principles calculations of hematite (α-FeO) by self-consistent DFT+U+V.

Owing to the confined Fe-3d orbitals and self-interaction error of exchange-correlation functionals, approximate DFT fails to describe iron oxides electronic structure and magnetic properties accurately. Hybrid DFT or DFT + U can solve these problems, but the former is expensive, and the latter only considers on-site interactions. Here, we used DFT + U + V, a DFT + U extension including inter-site interactions, to simulate the structural, magnetic, and electronic properties, along with Fe and O K-edge XAS spectra of α-FeO.

Hereditable variants of classical protein tyrosine phosphatase genes: Will they prove innocent or guilty?

Protein tyrosine phosphatases, together with protein tyrosine kinases, control many molecular signaling steps that control life at cellular and organismal levels. Impairing alterations in the genes encoding the involved proteins is expected to profoundly affect the quality of life-if compatible with life at all. Here, we review the current knowledge on the effects of germline variants that have been reported for genes encoding a subset of the protein tyrosine phosphatase superfamily; that of the thirty seven classical members.

Coatings of Cyclodextrin/Citric-Acid Biopolymer as Drug Delivery Systems: A Review.

In the early 2000s, a method for cross-linking cyclodextrins (CDs) with citric acid (CTR) was developed. This method was nontoxic, environmentally friendly, and inexpensive compared to the others previously proposed in the literature. Since then, the CD/CTR biopolymers have been widely used as a coating on implants and other materials for biomedical applications.

Effect of High-Pressure Treatments on the Properties of Food Packaging Materials with or without Antimicrobials.

The aim of this research work was the comparative study of the different properties of interest in the case of plastic materials for food use before and after being subjected to treatment by high hydrostatic pressure (HHP) as well as the impact of additivation with antimicrobials. This method of food preservation is currently on the rise and is of great interest because it is possible to extend the shelf life of many foods without the need for the use of additives or thermal processing, as is the case with other preservation methods currently used. The effects of HHP treatment (680 MPa for 8 min) on plastic materials commonly used in the food industry were studied.

Correlation of expression of Major Vault Protein with androgen receptor and immune checkpoint protein B7-H3, and with poor prognosis in prostate cancer.

Prostate cancer diagnosis and early stratification is an important aspect to avoid undertreatment of high-risk prostate cancer patients. Major Vault Protein (MVP) has been proposed as a prognostic biomarker in prostate cancer. PTEN and the immune checkpoint protein B7-H3 interact with MVP and are important in prostate cancer progression and therapy response.

Hopes on immunotherapy targeting B7-H3 in neuroblastoma.

Neuroblastoma is one of the most aggressive cancer forms in children, with highly heterogenous clinical manifestations ranging from spontaneous regression to high metastatic capacity. High-risk neuroblastoma has the highest mortality rates of all pediatric cancers, highlighting the urgent need for effective novel therapeutic interventions. B7-H3 immune checkpoint protein is highly expressed in neuroblastoma, and it is involved in oncogenic signaling, tumor cell plasticity, and drug resistance.

Effects of Sugar Beet Silage, High-Moisture Corn, and Corn Silage Feed Supplementation on the Performance of Dairy Cows with Restricted Daily Access to Pasture.

A study was undertaken to assess the effect of supplementation with sugar beet silage, corn silage, or high-moisture corn on dairy performance, rumen, and plasma metabolites in dairy cows under conditions of restricted grazing in spring. Eighteen multiparous Holstein Friesian cows, stratified for milk yield (39.4 kg/day ± 3.