Efficacy of pembrolizumab in microsatellite-stable, tumor mutational burden-high metastatic colorectal cancer: genomic signatures and clinical outcomes.

Background: Pembrolizumab, an immune checkpoint inhibitor (ICI), shows significant survival benefits in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but its efficacy in microsatellite-stable (MSS) mCRC is limited. Although ICIs are effective in tumor mutational burden-high (TMB-H) solid tumors, the impact on MSS-TMB-H mCRC, a rare subset within MSS mCRC, remains unclear.

Materials And Methods: We conducted a retrospective analysis using clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) repository in Japan.

Molecular orientation of dielectric layers at indigo/dielectric interfaces impacts the ordering of indigo films in organic field-effect transistors.

Organic multilayer systems, which are stacked layers of different organic materials, are used in various organic electronic devices such as organic light-emitting diodes (OLEDs) and organic field-effect transistors (OFETs). In particular, OFETs are promising as key components in flexible electronic devices. In this study, we investigated how the inclusion of an insulating tetratetracontane (TTC) interlayer in ambipolar indigo-based OFETs can be used to alter the crystallinity and electrical properties of the indigo charge transport layer.

Plasma and serum concentrations of VEGF-A121, but not of VEGF-A165, increase post-bevacizumab administration.

Background: VEGF-A concentrations were measured in the blood of bevacizumab-treated cancer patients in previous studies, but a consensus has not formed that would develop VEGF-A into a clinical biomarker. Recently, methods to strictly distinguish between the VEGF-A isoforms have been developed but have not yet been applied to cancer patients undergoing bevacizumab treatment.

Methods: An ELISA that strictly distinguishes between VEGF-A121 and VEGF-A165-the major isoforms of VEGF-A-and a commercially available ELISA for VEGF-A are used to determine the concentration of VEGF-A121, VEGF-A165, and VEGF-A in the blood of 12 patients with advanced colorectal cancer receiving bevacizumab therapy.

The Vascular Endothelial Growth Factor-A121/Vascular Endothelial Growth Factor-A165 Ratio as a Predictor of the Therapeutic Response to Immune Checkpoint Inhibitors in Gastric Cancer.

Background/objectives: The response rate to immune checkpoint inhibitor (ICI) therapy is limited. Further, there is a need to discover biomarkers to predict therapeutic efficacy. The vascular endothelial growth factor (VEGF) is strongly associated with intra-tumoral immunity; however, its utility as a marker remains unknown.

Impact of Genomic Alterations on Efficacy of Trastuzumab Deruxtecan Against Human Epidermal Growth Factor Receptor-2-Positive Advanced Gastric Cancer.

Purpose: The impact of genomic alterations on response and resistance to trastuzumab deruxtecan (T-DXd) has not been elucidated. Thus, we sought to identify factors predicting sensitivity to T-DXd in gastric or gastroesophageal junction (G/GEJ) cancer.

Methods: We conducted a retrospective study using real-world clinical data and next-generation sequencing-based comprehensive genomic profiling (CGP) data from patients with advanced G/GEJ cancers, collected by the nationwide database in Japan.

Treatment with lysophosphatidic acid improves glomerulonephritis through the suppression of macrophage activation in a murine model of systemic lupus erythematosus.

Objectives: Several therapeutic agents have been developed and used for the clinical treatment of systemic lupus erythematosus (SLE). In cases where SLE is accompanied by severe organ failures, such as neuropsychiatric lupus erythematosus (NPSLE) and acute onset of lupus nephritis, the use of potent immunosuppressive drugs, such as cyclophosphamide, is necessary. However, potent immunosuppressive drugs are known to increase infection risks.

A heterozygous germline deletion within USP8 causes severe neurodevelopmental delay with multiorgan abnormalities.

Ubiquitin-specific protease 8 (USP8) is a deubiquitinating enzyme involved in deubiquitinating the enhanced epidermal growth factor receptor for escape from degradation. Somatic variants at a hotspot in USP8 are a cause of Cushing's disease, and a de novo germline USP8 variant at this hotspot has been described only once previously, in a girl with Cushing's disease and developmental delay. In this study, we investigated an exome-negative patient with severe developmental delay, dysmorphic features, and multiorgan dysfunction by long-read sequencing, and identified a 22-kb de novo germline deletion within USP8 (chr15:50469966-50491995 [GRCh38]).

The impact of COVID-19 on Japanese patients with eosinophilic gastrointestinal disorders during the vaccination era.

Background: Eosinophilic gastrointestinal disorders (EGIDs) are chronic allergic diseases categorized as eosinophilic esophagitis (EoE) and non-EoE EGIDs. Few studies regarding the association between EGIDs and coronavirus disease 2019 (COVID-19) have been reported. Although most Japanese individuals received the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, the incidence of COVID-19 remained high in 2022.

SGLT2 and SGLT1 inhibitors suppress the activities of the RVLM neurons in newborn Wistar rats.

Hypertension is well-known to often coexist with diabetes mellitus (DM) in humans. Treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors has been shown to decrease both the blood glucose and the blood pressure (BP) in such patients. Some reports show that SGLT2 inhibitors improve the BP by decreasing the activities of the sympathetic nervous system.

Preferential B cell differentiation by combined immune checkpoint blockade for renal cell carcinoma is associated with clinical response and autoimmune reactions.

Combined immune checkpoint blockade (ICB) is effective therapy for renal cell carcinoma (RCC). However, the dynamic changes in circulating B cells induced by combined ICB have not been clarified. The present study prospectively examined 22 patients scheduled to receive ICB for unresectable or metastatic RCC between March 2018 and August 2021.

Risk factors for adverse events associated with endoscopic submucosal dissection for superficial pharyngeal cancer.

Background: Superficial pharyngeal cancer can be treated with curative intent while preserving function using minimally invasive peroral endoscopic resection techniques such as endoscopic submucosal dissection (ESD). However, severe adverse events occasionally occur, such as laryngeal edema requiring temporary tracheotomy and fistula formation. Therefore, we investigated the risk factors for adverse events associated with ESD for superficial pharyngeal cancer.

VEGF-A165 is the predominant VEGF-A isoform in platelets, while VEGF-A121 is abundant in serum and plasma from healthy individuals.

Vascular endothelial growth factor A (VEGF-A) plays pivotal roles in regulating tumor angiogenesis as well as physiological vascular function. The major VEGF-A isoforms, VEGF-A121 and VEGF-A165, in serum, plasma, and platelets have not been exactly evaluated due to the lack of the appropriate assay system. Antibodies against human VEGF-A121 and VEGF-A165 (hVEGF-A121 and hVEGF-A165) were successfully produced and Enzyme-Linked ImmunoSorbent Assay (ELISA) for hVEGF-A121 and hVEGF-A165 were separately created by these monoclonal antibodies.