Inhibition of PTPN3 Expressed in Activated Lymphocytes Enhances the Antitumor Effects of Anti-PD-1 Therapy in Head and Neck Cancer, Especially in Hypoxic Environments.

In the tumor microenvironment, wherein cytotoxic lymphocytes interact with cancer cells, lymphocyte exhaustion, an immune checkpoint inhibitor target, is promoted. However, the efficacy of these inhibitors is limited, and improving response rates remains challenging. We previously reported that protein tyrosine phosphatase nonreceptor type (PTPN) 3 is a potential immune checkpoint molecule for activated lymphocytes and that PTPN3 inhibition should be a focus area for cancer immunotherapy development.

Biological and genetic characterization of a newly established human external auditory canal carcinoma cell line, SCEACono2.

Squamous cell carcinoma of the external auditory canal (EACSCC) is an extraordinarily rare and aggressive malignant disease. Establishment of EACSCC cell line with robust molecular characteristics is essential for the basic and translational research of EACSCC. Here, we show the newly established EACSCC cell line SCEACono2, derived from a patient with well-to-moderately differentiated EACSCC.

Development of a plasma-free amino acid-based risk score for the incidence of cardiovascular diseases in a general population: The Nagahama study.

Background & Aims: Levels of circulating amino acids (AAs) have been suggested to be associated with cardiovascular diseases (CVDs). This study aimed to develop a plasma-free amino acid (PFAA)-based CVD risk-prediction model in a general population.

Methods: The study participants consisted of 9220 community residents (mean age, 53.

Dietary amino acid intake and sleep duration are additively involved in future cognitive decline in Japanese adults aged 60 years or over: a community-based longitudinal study.

Background: Sleep duration and amino acid intake are independently associated with cognitive decline. This study aimed to determine the longitudinal association between sleep duration and cognitive impairment incidence and to examine the involvement of diet, particularly amino acid intake, in these associations in community dwellers.

Methods: In this longitudinal study in a community-based setting, we analyzed data from 623 adults aged 60-83 years without cognitive impairment at baseline.

PTPN3 inhibition contributes to the activation of the dendritic cell function to be a promising new immunotherapy target.

Purpose: In a previous study, protein tyrosine phosphatase non-receptor type (PTPN) 3 was identified as an immune checkpoint molecule in lymphocytes, and its potential as a novel target for cancer immunotherapy was anticipated. However, evaluation of dendritic cell (DC) function as antigen-presenting cells is critical for the development of immunotherapy. In this study, we aimed to analyze the biological effect of PTPN3 on DCs induced from human peripheral blood monocytes obtained from healthy individuals.

C4orf47 contributes to the dormancy of pancreatic cancer under hypoxic conditions.

In our comprehensive analysis of pancreatic cancer pathology, we found that the C4orf47 molecule was upregulated in hypoxic environments. C4orf47 is reported to be a centrosome-associated protein, but its biological significance in cancer is completely unknown; therefore, we assessed its role in pancreatic cancer. We found that C4orf47 was a direct target of HIF-1α and is upregulated in hypoxic conditions, in which it suppressed the cell cycle and inhibits cell proliferation through up-regulation of the cell cycle repressors Fbxw-7, P27, and p57; and the down-regulation of the cell cycle promoters c-myc, cyclinD1, and cyclinC.

Outcomes of embolization procedures for type II endoleaks following endovascular abdominal aortic repair.

Objective: The objective of this study was to investigate the mid-term outcomes of embolization procedures for type II endoleak after endovascular abdominal aortic repair, and clarify the risk factors for aneurysm enlargement after embolization procedures.

Methods: This was a retrospective multicenter registry study enrolling patients who underwent embolization procedures for type II endoleaks after EVAR from January 2012 to December 2018 at 19 Japanese centers. The primary end point was the rate of freedom from aneurysm enlargement, more than 5 mm in the aortic maximum diameter, after an embolization procedure.

Synthesis of Microporous Aluminosilicate by Direct Thermal Activation of Phenyl-Substituted Single-Source Aluminosilicate Molecular Precursors.

The construction of aluminosilicates from versatile molecular precursors (MPs) represents a promising alternative strategy to conventional processes based on monomeric molecular or polymeric Al and Si sources. However, the use of MPs often suffers from drawbacks such as the decomposition of the core structures in the presence of solvents, acids, or bases. In this work, we demonstrate a simple thermal synthesis of porous aluminosilicates from single-source spiro-7-type MPs that consist of a tetrahedral Al atom and six Si atoms functionalized with 12 phenyl (Ph) groups, (C)[Al{PhSi(OSiPhO)}] (; C = pyridinium cation (PyH), Na, K, Rb, or Cs), without using a solvent or activator.

Effects of an essential amino acid mixture on behavioral and psychological symptoms of dementia and executive function in patients with Alzheimer's disease: A double-blind, randomized, placebo-controlled exploratory clinical trial.

Background: The increasing number of dementia patients has become a global social problem. Amino acids are known to be used as precursors of neurotransmitters in the brain. Amino acid mixtures as a supplement may be used as a solution to Alzheimer's symptoms.

Clinical significance of plasma-free amino acids and tryptophan metabolites in patients with non-small cell lung cancer receiving PD-1 inhibitor: a pilot cohort study for developing a prognostic multivariate model.

Background: Amino acid metabolism is essential for tumor cell proliferation and regulation of immune cell function. However, the clinical significance of free amino acids (plasma-free amino acids (PFAAs)) and tryptophan-related metabolites in plasma has not been fully understood in patients with non-small cell lung cancer (NSCLC) who receive immune checkpoint inhibitors.

Methods: We conducted a single cohort observational study.

[Cross-sectional association between the amino acid intake and episodic memory in middle- and old-aged community dwellers].

Aim: The specific amino acid intake has been suggested to be positively associated with the cognitive function. However, few reports have investigated the association between the amino acid intake and episodic memory (EM). Therefore, we investigated this association.

PTPN3 is a potential target for a new cancer immunotherapy that has a dual effect of T cell activation and direct cancer inhibition in lung neuroendocrine tumor.

In our previous study, we found that inhibition of protein tyrosine phosphatase non-receptor type 3 (PTPN3), which is expressed in lymphocytes, enhances lymphocyte activation, suggesting PTPN3 may act as an immune checkpoint molecule. However, PTPN3 is also expressed in various cancers, and the biological significance of PTPN3 in cancer cells is still not well understood, especially for lung neuroendocrine tumor (NET).Therefore, we analyzed the biological significance of PTPN3 in small cell lung cancer and examined the potential for PTPN3 inhibitory treatment as a cancer treatment approach in lung NET including small cell lung cancer (SCLC) and large cell neuroendocrine cancer (LCNEC).

Establishment and characterization of a primary cell culture derived from external auditory canal squamous cell carcinoma.

There are no human cancer cell lines of external auditory canal origin available for research use. This report describes the establishment of a culture condition for external auditory canal squamous cell carcinoma, derived from human tumor tissue. Successive squamous cell carcinoma colonies were dissociated by trypsin, subcultured, and maintained on a feeder layer (MMC-TIG-1-20), yielding a clonally proliferating cell culture.

Anatomy of Left Inferior Phrenic Vein in Patients Without Portal Hypertension.

The left inferior phrenic vein (LIPV) can be an origin of a gastrorenal shunt from gastric varices. The purpose of our study was to evaluate the angiographic anatomy of the LIPV, particularly anastomoses of the LIPV with the portal vein (PV). Of 240 patients with primary aldosteronism who underwent adrenal venous sampling from April 2011 to July 2019, 236 had normal liver and renal function and were included in this study.

GLI2 but not GLI1/GLI3 plays a central role in the induction of malignant phenotype of gallbladder cancer.

We previously reported that Hedgehog (Hh) signal was enhanced in gallbladder cancer (GBC) and was involved in the induction of malignant phenotype of GBC. In recent years, therapeutics that target Hh signaling have focused on molecules downstream of smoothened (SMO). The three transcription factors in the Hh signal pathway, glioma‑associated oncogene homolog 1 (GLI1), GLI2, and GLI3, function downstream of SMO, but their biological role in GBC remains unclear.

NFκB and TGFβ contribute to the expression of PTPN3 in activated human lymphocytes.

We previously reported that protein tyrosine phosphatase non-receptor type 3 (PTPN3), which is upregulated in activated lymphocytes, acts as an immune checkpoint. However, the mechanism by which PTPN3 expression is enhanced in activated lymphocytes is unknown. In this study, we analyzed the mechanism of PTPN3 expression in activated lymphocytes with a view for developing a novel immune checkpoint inhibitor that suppresses PTPN3.

Transarterial fiducial marker implantation for CyberKnife radiotherapy to treat pancreatic cancer: an experience with 14 cases.

Purpose: The purpose of this study was to evaluate the safety and feasibility of transarterial fiducial marker implantation for CyberKnife radiotherapy to treat locally advanced pancreatic cancer.

Materials And Methods: Fifteen pancreatic cancer patients were enrolled for transarterial marker implantation. Embolization platinum coils were implanted as a fiducial marker within 20 mm of the cancer edge, and preferably within 3 mm.

Patched 1-interacting Peptide Represses Fibrosis in Pancreatic Cancer to Augment the Effectiveness of Immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is resistant to immunotherapy. As a factor of resistance, the dense fibrosis of this cancer acts as a barrier to inhibit immune cell infiltration into a tumor. We examined the influence of a Hedgehog signal inhibitor, Patched 1-interacting peptide, on fibrosis, infiltration of immune cells, and immunotherapeutic effects on PDAC.

PTPN3 expressed in activated T lymphocytes is a candidate for a non-antibody-type immune checkpoint inhibitor.

It has been shown that protein tyrosine phosphatase non-receptor type (PTPN) 3 inhibits T-cell activation. However, there is no definitive conclusion about how the inhibition of PTPN3 in lymphocytes affects immune functions in human lymphocytes. In the present study, we showed that PTPN3 inhibition significantly contributes to the enhanced activation of activated human lymphocytes.

Methods for Absolute Quantification of Human Plasma Free Amino Acids by High-Performance Liquid Chromatography/Electrospray Ionization Mass Spectrometry Using Precolumn Derivatization.

Plasma free amino acid (PFAA) concentrations in humans are affected by various diseases. However, the variations caused are not dramatic, so a high accurate and precise method for analyzing PFAAs is required. The PFAA analysis protocol described in this chapter covers blood sampling, sample pretreatment, amino acid derivatization, and LC-MS analysis.