Tumor Infiltrating Effector Regulatory T Cells Express VEGF Receptor 2 in Patients With Colorectal Cancer.

Background/aim: Regulatory T cells (Tregs) suppress various anti-tumor immune responses in the tumor microenvironment (TME) and their control is considered essential to enhancing efficacy of cancer immunotherapy. The purpose of the study was to evaluate the strategy to regulate Tregs through the vascular endothelial growth factor (VEGF) pathway.

Materials And Methods: We evaluated VEGF receptor (VEGFR) expression in subtypes of Tregs by analysis of public databases and through flow cytometry by investigating surgically resected specimens and peripheral blood mononuclear cells (PBMCs) from 26 patients with advanced colorectal cancer (CRC).

TGFβ-Responsive Stromal Activation Occurs Early in Serrated Colorectal Carcinogenesis.

Activated TGFβ signaling in the tumor microenvironment, which occurs independently of epithelial cancer cells, has emerged as a key driver of tumor progression in late-stage colorectal cancer (CRC). This study aimed to elucidate the contribution of TGFβ-activated stroma to serrated carcinogenesis, representing approximately 25% of CRCs and often characterized by oncogenic mutations. We used a transcriptional signature developed based on TGFβ-responsive, stroma-specific genes to infer TGFβ-dependent stromal activation and conducted in silico analyses in 3 single-cell RNA-seq datasets from a total of 39 CRC samples and 12 bulk transcriptomic datasets consisting of 2014 CRC and 416 precursor samples, of which 33 were serrated lesions.

Small bowel fistula with colorectal cancer and mesenteric lymph node metastasis: a report of two cases.

A 65-year-old man presented to our hospital with complaints of diarrhea. Computed tomography showed a fistula with the small intestine, and a single incision laparoscopic low anterior resection for rectum with D3 dissection and partial resection of the small intestine were performed. Lymph node dissection, including a part of the inflow vessel area, was also performed because lymph node swelling was observed in the mesentery of the small intestine around the fistula.

M2 tumor-associated macrophages resist to oxidative stress through heme oxygenase-1 in the colorectal cancer tumor microenvironment.

M2 tumor-associated macrophages (M2-TAMs) promote cancer cell proliferation and metastasis in the TME. Our study aimed to elucidate the mechanism of increased frequency of M2-TAMs infiltration in the colorectal cancer (CRC)-TME, focusing on the resistance to oxidative stress through nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In this study, we evaluated the correlation between M2-TAM signature and mRNA expression of antioxidant related genes using public datasets, and the expression level of antioxidants in M2-TAMs by flow cytometry and the prevalence of M2-TAMs expressing antioxidants by immunofluorescence staining using surgically resected specimens of CRC (n = 34).

Laparoscopic total gastrectomy performed for juvenile polyposis of the stomach: A case report.

Introduction And Importance: Juvenile polyposis of the stomach (JPST) is a very rare disease and has been reported to have malignant potential. Total gastrectomy has been recommended as a standard treatment. Recently, the usefulness of laparoscopic surgery for this disease has been reported; however, in laparoscopic surgery, maintaining the surgical space is difficult because of the distended and thickened stomach wall that polyposis causes.

Antihypertensive drug prescription trends for pregnant women with hypertension in acute hospitals in Japan.

Hypertensive disorders of pregnancy cause maternal organ damage. Therefore, appropriate management with antihypertensive medication is required from the first trimester. We aimed to clarify the antihypertensive drug prescription trends in pregnant women with hypertension in Japan.

Immune escape mechanism behind resistance to anti-PD-1 therapy in gastrointestinal tract metastasis in malignant melanoma patients with multiple metastases.

Immunotherapy targeting the PD-1 axis has recently become a standard treatment for patients with malignant melanoma. However, approximately 25% of reported malignant melanoma patients who initially responded to immunotherapy with anti-PD-1 mAb had progressive disease, and the immune escape mechanism behind resistance to anti-PD-1 therapy is not yet fully understood in the clinical setting. In the present study, we included four malignant melanoma patients, in whom multiple metastases other than gastrointestinal tract metastasis had disappeared or were controlled under multidisciplinary treatment that included anti-PD-1 therapy.

SH2D4A downregulation due to loss of chromosome 8p is associated with poor prognosis and low T cell infiltration in colorectal cancer.

Background: Colorectal cancer (CRC) develops through chromosomal instability (CIN) or microsatellite instability (MSI) due to deficient mismatch-repair (dMMR). We aimed to characterise novel cancer-associated genes that are downregulated upon malignant transformation in microsatellite stable (MSS) CRCs, which typically exhibit CIN with proficient mismatch-repair (pMMR).

Methods: Comprehensive screening was conducted on adenomas, MSI/MSS CRCs and cell lines, followed by copy number analysis, and their genetic and prognostic relevance was confirmed in microarray and RNA-seq cohorts (n = 3262, in total).

[Immunotherapy Targeting Tumor-Associated Carbohydrate Antigens in Deficient Mismatch Repair Colorectal Cancer].

The Tn antigen is the most prevalent tumor-associated carbohydrate antigen. It interacts with macrophage galactose-specific lectin(MGL)on dendric cells and macrophages, driving immune inhibitory signals. Colorectal cancer(CRC)exhibiting deficient mismatch repair(dMMR)is characterized by tumor-infiltrating lymphocytes(TILs), the expression of immune checkpoint molecules, and immune evasion.

The Expression of Immune Checkpoint Receptors and Ligands in the Colorectal Cancer Tumor Microenvironment.

Background/aim: The limited efficacy of immune checkpoint inhibitors in colorectal cancer (CRC) is likely due to immunosuppressive mechanisms including T cell exhaustion caused by inhibitory immune checkpoints in the tumor microenvironment.

Materials And Methods: We investigated the expression status of the inhibitory immune checkpoint receptors on tumor-infiltrating T cells and their ligands on tumor cells by flow cytometry and immunohistochemistry, using surgically-resected specimens of CRC.

Results: Flow cytometry analysis indicated that TIM-3, TIGIT, and PD-1 were expressed on tumor-infiltrating CD4+ (8.

The effects of T-DXd on the expression of HLA class I and chemokines CXCL9/10/11 in HER2-overexpressing gastric cancer cells.

Trastuzumab deruxtecan (T-DXd), a HER2-targeting antibody-drug conjugate with a topoisomerase I inhibitor deruxtecan (DXd), exhibits an excellent anti-tumor effect in previously treated HER2-positive tumors. A recent study demonstrated that T-DXd not only suppressed tumor growth but also enhanced anti-tumor immunity through increasing the number of tumor-infiltrating CD8 T cells and enhancement of major-histocompatibility-complex class I expression on tumor cells in a mouse model. However, the effect of T-DXd on anti-tumor immune responses in human cancers is largely unknown.

Drug prescription for attention deficit hyperactivity disorder drugs in pediatric outpatients: A retrospective survey of Japanese administrative data (2012-2018).

We aimed to clarify the prescription trend of ADHD drugs in Japanese pediatric outpatients. From January 2012 to December 2018, we evaluated the trends of prescribing methylphenidate-osmotic-controlled release oral delivery system (OROS), atomoxetine, and guanfacine as monotherapy. In boys, methylphenidate-OROS and atomoxetine prescriptions decreased from 46.

Tn Antigen Expression Defines an Immune Cold Subset of Mismatch-Repair Deficient Colorectal Cancer.

Colorectal cancer (CRC) cells often express Tn antigen, a tumor-associated truncated immature O-glycan (GalNAcα-O-Ser/Thr) that can promote tumor progression. Immunotherapies against Tn antigen have been developed and are being evaluated in clinical trials. Tn antigen can also be considered a novel immune checkpoint that induces immunosuppressive signaling through glycan-biding lectins to lead effector T cell apoptosis.

Effect of azygos arch preservation during thoracoscopic esophagectomy on facilitation of postoperative refilling.

Purpose: In esophageal cancer surgery, the significance of preserving the azygos arch during thoracoscopic esophagectomy remains unknown. To determine the significance, we examined the difference in postoperative courses between patients who underwent an azygos arch-preserving technique and patients whose azygos arch had been dissected.

Methods: We retrospectively analyzed 119 patients with esophageal cancer who underwent thoracoscopic esophagectomy from January 2017 to December 2019.

The hybrid procedure of thoracoscopic and hand-assisted laparoscopic resection of an esophageal gastrointestinal stromal tumor: A case report.

Esophageal gastrointestinal stromal tumors (E-GIST) are very rare tumors, and there is no consensus regarding the optimal surgical approach for E-GISTs. Here, we report a case of a large E-GIST that was resected via video-assisted thoracoscopic surgery (VATS) and hand-assisted laparoscopic surgery (HALS). When examining for comorbidities of myasthenia gravis using computed tomography, a 7-cm-sized tumor was detected in the lower esophagus of a 68-year-old woman.

Effects of AS2819899, a novel selective PI3Kδ inhibitor, in a NZB/W F1 mouse lupus-like nephritis model.

Phosphoinositide 3-kinases generate lipid-based second messengers that control an array of intracellular signaling pathways. In particular, phosphoinositide 3-kinases delta (PI3Kδ) is expressed primarily in hematopoietic cells and plays an important role in B-cell development and function. B cells play a critical role in autoimmune diseases by producing autoantibodies.

Grade 3 well-differentiated neuroendocrine tumor of the rectum: a case report.

Background: The 2019 revised World Health Organization (WHO) classification of tumors of endocrine organs classifies grade 3 gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN G3) into well-differentiated tumors (NET G3) and poorly differentiated carcinomas (NEC G3). There are few reported cases of NET G3 occurring in the rectum.

Case Presentation: A 71-year-old man complained of bright red blood in his stool.

Dehydrative Allylation of α C(sp)-H Bonds of Alkylamines with Allylic Alcohols.

Herein reported is a dehydrative coupling reaction of alkyl amines with allylic alcohols promoted by co-operation of photoredox and palladium catalysts. A range of homoallylic amines are efficiently synthesized. A mechanistic study suggests that an in situ generated carboxylic acid activates an allylic alcohol to facilitate its oxidative addition onto palladium.

Impact of endoscopic resection on the choice of surgical procedure in patients with additional laparoscopic gastrectomy.

Background: Additional surgery is recommended for patients with noncurative resection after endoscopic submucosal dissection (ESD) for early gastric cancer. Additional resection requires the excision of an area larger than that of the resected mucosa in ESD, which is larger than the lesion, with convergence of the gastric mucosa due to scarring. Thus, the selection of the surgical procedure for lesion removal in specific areas can be affected by ESD.