Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review.

Tyrosine kinase inhibitors have been successfully developed in combination with immune checkpoint inhibitors to treat advanced renal cell carcinoma (RCC), further advancing treatment. While safety profiles are generally manageable with combination regimens, overlapping adverse events (AEs) and immune-related AEs can make treatment more complex. The CheckMate 9ER study evaluated the tyrosine kinase inhibitor cabozantinib in combination with the anti-programmed cell death protein-1 antibody nivolumab in patients with previously untreated advanced RCC.

Cabozantinib plus Nivolumab Phase I Expansion Study in Patients with Metastatic Urothelial Carcinoma Refractory to Immune Checkpoint Inhibitor Therapy.

Purpose: This study investigated the efficacy and tolerability of cabozantinib plus nivolumab (CaboNivo) in patients with metastatic urothelial carcinoma (mUC) that progressed on checkpoint inhibition (CPI).

Patients And Methods: A phase I expansion cohort of patients with mUC who received prior CPI was treated with cabozantinib 40 mg/day and nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary goal was objective response rate (ORR) per RECIST v.

Longitudinal trajectories of lifetime body shape and prostate cancer angiogenesis.

Angiogenesis potentially underlies the pathway between excess adiposity and prostate carcinogenesis. This study examined the association between lifetime body shape trajectories and prostate cancer angiogenesis. 521 prostate cancer patients who underwent prostatectomy or transurethral resection between 1986 and 2000 were enrolled from the Health Professionals Follow-up Study.

Multifaceted Regulation of Akt by Diverse C-Terminal Post-translational Modifications.

Akt is a Ser/Thr protein kinase that regulates cell growth and metabolism and is considered a therapeutic target for cancer. Regulation of Akt by membrane recruitment and post-translational modifications (PTMs) has been extensively studied. The most well-established mechanism for cellular Akt activation involves phosphorylation on its activation loop on Thr308 by PDK1 and on its C-terminal tail on Ser473 by mTORC2.

Early phase clinical studies of AR-42, a histone deacetylase inhibitor, for neurofibromatosis type 2-associated vestibular schwannomas and meningiomas.

Objectives: Two pilot studies of AR-42, a pan-histone deacetylase inhibitor, in human neurofibromatosis type 2 (NF2), vestibular schwannomas (VS), and meningiomas are presented. Primary endpoints included safety, and intra-tumoral pharmacokinetics (PK) and pharmacodynamics (PD).

Methods: Pilot 1 is a subset analysis of a phase 1 study of AR-42 in solid tumors, which included NF2 or sporadic meningiomas.

Evolution of Fc Receptor-Like Scavenger in Mammals.

Fc receptor-like (FCRL) molecules comprise a large family of receptors, homologous to the receptors for the Fc portion of immunoglobulins (FCR). Within this family, an unusual gene known to exist in mice, rats and dogs, termed , encodes a chimeric protein with both Ig-like FCRL and type B scavenger-receptor cysteine-rich (SRCR)-like domains. In mice, is located next to the and genes.

Patient Experiences with Screening and Assistance for Social Isolation in Primary Care Settings.

Background: Social isolation is a known predictor of mortality that disproportionately affects vulnerable populations in the USA. Although experts began to recognize it as a public health crisis prior to 2020, the novel coronavirus pandemic has accelerated recognition of social isolation as a serious threat to health and well-being.

Objective: Examine patient experiences with screening and assistance for social isolation in primary care settings, and whether patient experiences with these activities are associated with the severity of reported social isolation.

A phase 1 trial of the histone deacetylase inhibitor AR-42 in patients with neurofibromatosis type 2-associated tumors and advanced solid malignancies.

Purpose: Given clinical activity of AR-42, an oral histone deacetylase inhibitor, in hematologic malignancies and preclinical activity in solid tumors, this phase 1 trial investigated the safety and tolerability of AR-42 in patients with advanced solid tumors, including neurofibromatosis type 2-associated meningiomas and schwannomas (NF2). The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). Secondary objectives included determining pharmacokinetics and clinical activity.

Advanced adenomas may be a red flag for hereditary cancer syndromes.

Background: 16-25% of colorectal cancers (CRCs) diagnosed under age 50 are associated with hereditary cancer syndromes. Advanced adenomas are considered precursors to CRC. Although polyp removal prevents cancer, polypectomy does not change underlying genetic risk.

Induced pluripotent stem cell technology for spinal cord injury: a promising alternative therapy.

Spinal cord injury has long been a prominent challenge in the trauma repair process. Spinal cord injury is a research hotspot by virtue of its difficulty to treat and its escalating morbidity. Furthermore, spinal cord injury has a long period of disease progression and leads to complications that exert a lot of mental and economic pressure on patients.

Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study.

Background: Higher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood.

Methods: We examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC.

CDK5 Inhibition Abrogates TNBC Stem-Cell Property and Enhances Anti-PD-1 Therapy.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, in which the higher frequency of cancer stem cells (CSCs) correlates with the poor clinical outcome. An aberrant activation of CDK5 is found to associate with TNBC progression closely. CDK5 mediates PPAR phosphorylation at its Ser 273, which induces CD44 isoform switching from CD44s to CD44v, resulting in an increase of stemness of TNBC cells.

B7-H3 augments the pro-angiogenic function of tumor-associated macrophages and acts as a novel adjuvant target for triple-negative breast cancer therapy.

B7-H3 is an immune checkpoint molecule from the B7 superfamily. It has been widely studied in tumor immune evasion in certain types of cancer. In our preliminary study, we found that B7-H3 is specifically enriched in tumor-associated macrophages (TAMs) in triple-negative breast cancer (TNBC) patients and strongly correlated with poor clinical prognosis.

Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects.

Background And Aims: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes.

Methods: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355).

Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors.

Purpose: We assessed the safety and efficacy of cabozantinib and nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignances.

Patients And Methods: Patients received escalating doses of CaboNivo or CaboNivoIpi. The primary objective was to establish a recommended phase II dose (RP2D).

Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.

Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry.

Live imaging of intra-lysosome pH in cell lines and primary neuronal culture using a novel genetically encoded biosensor.

Disorders of lysosomal physiology have increasingly been found to underlie the pathology of a rapidly growing cast of neurodevelopmental disorders and sporadic diseases of aging. One cardinal aspect of lysosomal (dys)function is lysosomal acidification in which defects trigger lysosomal stress signaling and defects in proteolytic capacity. We have developed a genetically encoded ratiometric probe to measure lysosomal pH coupled with a purification tag to efficiently purify lysosomes for both proteomic and evaluation of their function.

How to Apply Supervised Machine Learning Tools to MS Imaging Files: Case Study with Cancer Spheroids Undergoing Treatment with the Monoclonal Antibody Cetuximab.

As the field of mass spectrometry imaging continues to grow, so too do its needs for optimal methods of data analysis. One general need in image analysis is the ability to classify the underlying regions within an image, as healthy or diseased, for example. Classification, as a general problem, is often best accomplished by supervised machine learning strategies; unfortunately, conducting supervised machine learning on MS imaging files is not typically done by mass spectrometrists because a high degree of specialized knowledge is needed.

Randomized Double-Blind Phase II Study of Maintenance Pembrolizumab Versus Placebo After First-Line Chemotherapy in Patients With Metastatic Urothelial Cancer.

Purpose: Platinum-based chemotherapy for first-line treatment of metastatic urothelial cancer is typically administered for a fixed duration followed by observation until progression. "Switch maintenance" therapy with PD-1 blockade at the time of chemotherapy cessation may be attractive for mechanistic and pragmatic reasons.

Patients And Methods: Patients with metastatic urothelial cancer achieving at least stable disease on first-line platinum-based chemotherapy were enrolled.

Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position statement on multigene panel testing for patients with colorectal cancer and/or polyposis.

Multigene panel tests for hereditary cancer syndromes are increasingly utilized in the care of colorectal cancer (CRC) and polyposis patients. However, widespread availability of panels raises a number of questions including which patients should undergo testing, which genes should be included on panels, and the settings in which panels should be ordered and interpreted. To address this knowledge gap, key questions regarding the major issues encountered in clinical evaluation of hereditary CRC and polyposis were designed by the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position Statement Committee and leadership.

In situ metabolite and lipid analysis of GluN2D and wild-type mice after ischemic stroke using MALDI MSI.

The N-methyl-D-aspartate (NMDA) receptor is a crucial mediator of pathological glutamate-driven excitotoxicity and subsequent neuronal death in acute ischemic stroke. Although the roles of the NMDAR's composite GluN2A-C subunits have been investigated in this phenomenon, the relative importance of the GluN2D subunit has yet to be evaluated. Herein, GluN2D mice were studied in a model of ischemic stroke using MALDI FT-ICR mass spectrometry imaging to investigate the role of the GluN2D subunit of the NMDA receptor in brain ischemia.