Psoas Muscle Index as an Independent Predictor of Survival in Patients with Hepatocellular Carcinoma Receiving Systemic Targeted Therapy.

Background: This study aimed to investigate the usefulness of the psoas muscle index (PMI) as an independent predictor of survival after systemic targeted therapy initiation in patients with hepatocellular carcinoma (HCC).

Method: In total, 214 patients with HCC who underwent systemic targeted therapy at the Gifu University Hospital were enrolled. The correlation between the PMI and the skeletal muscle index (SMI) was assessed using Pearson's correlation coefficient (PCC).

Development of LAT1-Selective Nuclear Medicine Therapeutics Using Astatine-211.

We investigated nuclear medicine therapeutics targeting the L-type amino acid transporter 1 (LAT1). We previously reported that a nuclear medicine therapeutic drug using astatine 211 (At), an alpha-emitting nuclide that can be produced in an accelerator and targets LAT1 as a molecular target, is effective. The seed compound was 3-[At] Astato-α-methyl-L-tyrosine (At-AAMT-OH-L).

Comparison Length of Linker in Compound for Nuclear Medicine Targeting Fibroblast Activation Protein as Molecular Target.

Novel nuclear medicine therapeutics are being developed by labeling medium-molecular-weight compounds with short-lived alpha-emitting radionuclides. Fibroblast activation protein α (FAPα) is recognized as a highly useful molecular target, and its inhibitor, FAPI, is a compound capable of , both therapeutic and diagnostic, for cancer treatment. In this study, we compared the functions of two compounds that target FAPα: At-FAPI1 and At-FAPI2.

Glyburide Suppresses Inflammation-Related Colorectal Tumorigenesis Through Inhibition of NLRP3 Inflammasome.

Colorectal cancer represents one of the most serious complications of inflammatory bowel disease. The NLRP3 inflammasome plays a pivotal role in the onset and progression of inflammatory bowel disease and is also implicated in colorectal cancer. This study aimed to investigate whether NLRP3 deficiency or glyburide, a sulfonylurea used for diabetes management and known as an NLRP3 inhibitor, could suppress colitis and its related colorectal tumorigenesis.

Evaluation of Targeted Alpha Therapy Using [At]FAPI1 in Triple-Negative Breast Cancer Xenograft Models.

Triple-negative breast cancer (TNBC) presents limited therapeutic options and is associated with poor prognosis. Early detection and the development of novel therapeutic agents are therefore imperative. Fibroblast activation protein (FAP) is a membrane protein expressed on cancer-associated fibroblasts (CAFs) that plays an essential role in TNBC proliferation, migration, and invasion.

Vitamin D deficiency stratifies the risk of covert and overt hepatic encephalopathy in patients with cirrhosis: A retrospective cohort study.

Backgrounds & Aims: This study aimed to investigate the association between vitamin D deficiency and covert hepatic encephalopathy (CHE), overt hepatic encephalopathy (OHE) occurrence, and mortality in patients with cirrhosis.

Methods: This retrospective study reviewed 679 patients with cirrhosis. Vitamin D deficiency was defined as serum 25-hydorxyvitamin D (25-OHD) levels < 20 ng/mL.

Preclinical Evaluation of Biodistribution and Toxicity of [At]PSMA-5 in Mice and Primates for the Targeted Alpha Therapy against Prostate Cancer.

Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA) compound ([At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model.

Possibility of Cell Block Specimens from Overnight-Stored Bile for Next-Generation Sequencing of Cholangiocarcinoma.

The identification of anticancer therapies using next-generation sequencing (NGS) is necessary for the treatment of cholangiocarcinoma. NGS can be easily performed when cell blocks (CB) are obtained from bile stored overnight. We compared NGS results of paired CB and surgically resected specimens (SRS) from the same cholangiocarcinoma cases.

Asymptomatic intestinal tuberculosis of the terminal ileum diagnosed on colonoscopy: a case report and literature review.

Objective: Colonoscopy is useful in diagnosing intestinal tuberculosis. However, the terminal ileum is generally not examined during routine colonoscopy. Therefore, even with colonoscopy, the diagnosis can be missed in patients with lesions confined to the terminal ileum.

Dysphagia risk evaluated by the Eating Assessment Tool-10 is associated with health-related quality of life in patients with chronic liver disease.

Objective: This study aimed to reveal the prevalence and characteristics of individuals at risk of dysphagia in patients with chronic liver disease (CLD) and its association with health-related quality of life (HRQOL).

Methods: This cross-sectional study included 335 outpatients with CLD. Dysphagia risk, sarcopenia risk, malnutrition risk, and HRQOL were assessed using the Eating Assessment tool-10 (EAT-10), SARC-F, Royal Free Hospital-Nutrition Prioritizing Tool (RFH-NPT), and Chronic Liver Disease Questionnaire (CLDQ), respectively.

Production of [At]NaAt solution under GMP compliance for investigator-initiated clinical trial.

Background: The alpha emitter astatine-211 (At) is garnering attention as a novel targeted alpha therapy for patients with refractory thyroid cancer resistant to conventional therapy using beta emitter radioiodine (I). Herein, we aimed to establish a robust method for the manufacturing and quality control of [At]NaAt solution for intravenous administration under the good manufacturing practice guidelines for investigational products to conduct an investigator-initiated clinical trial.

Results: At was separated and purified via dry distillation using irradiated Bi plates containing At obtained by the nuclear reaction of Bi(He, 2n)At.

Animal naming test stratifies the risk of falls and fall-related fractures in patients with cirrhosis.

This study aimed to determine the relationship between animal naming test (ANT), falls, and fall-related fractures in patients with cirrhosis. Cognitive impairment and frailty were assessed using ANT and Karnofsky performance status (KPS), respectively. Factors stratifying the risk of previous falls and fall-related fractures within 1 year were assessed using a logistic regression model.

Serum MYCN as a predictive biomarker of prognosis and therapeutic response in the prevention of hepatocellular carcinoma recurrence.

The proto-oncogene MYCN expression marked a cancer stem-like cell population in hepatocellular carcinoma (HCC) and served as a therapeutic target of acyclic retinoid (ACR), an orally administered vitamin A derivative that has demonstrated promising efficacy and safety in reducing HCC recurrence. This study investigated the role of MYCN as a predictive biomarker for therapeutic response to ACR and prognosis of HCC. MYCN gene expression in HCC was analyzed in the Cancer Genome Atlas and a Taiwanese cohort (N = 118).

Comparison of Nuclear Medicine Therapeutics Targeting PSMA among Alpha-Emitting Nuclides.

Currently, targeted alpha therapy (TAT) is a new therapy involving the administration of a therapeutic drug that combines a substance of α-emitting nuclides that kill cancer cells and a drug that selectively accumulates in cancer cells. It is known to be effective against cancers that are difficult to treat with existing methods, such as cancer cells that are widely spread throughout the whole body, and there are high expectations for its early clinical implementation. The nuclides for TAT, including Tb, At, Bi, Pb (for Bi), Ra, Ac, Th, and U, are known.

Development and Utility of an Imaging System for Internal Dosimetry of Astatine-211 in Mice.

In targeted radionuclide therapy, determining the absorbed dose of the ligand distributed to the whole body is vital due to its direct influence on therapeutic and adverse effects. However, many targeted alpha therapy drugs present challenges for in vivo quantitative imaging. To address this issue, we developed a planar imaging system equipped with a cadmium telluride semiconductor detector that offers high energy resolution.

A Novel Mouse Model of Intrahepatic Cholangiocarcinoma Induced by Azoxymethane.

Cholangiocarcinoma is the second most common primary cancer of the liver and has a poor prognosis. Various animal models, including carcinogen-induced and genetically engineered rodent models, have been established to clarify the mechanisms underlying cholangiocarcinoma development. In the present study, we developed a novel mouse model of malignant lesions in the biliary ducts induced by the administration of the carcinogen azoxymethane to obese C57BLKS/J-db/db mice.

Targeting transglutaminase 2 mediated exostosin glycosyltransferase 1 signaling in liver cancer stem cells with acyclic retinoid.

Transglutaminase 2 (TG2) is a multifunctional protein that promotes or suppresses tumorigenesis, depending on intracellular location and conformational structure. Acyclic retinoid (ACR) is an orally administered vitamin A derivative that prevents hepatocellular carcinoma (HCC) recurrence by targeting liver cancer stem cells (CSCs). In this study, we examined the subcellular location-dependent effects of ACR on TG2 activity at a structural level and characterized the functional role of TG2 and its downstream molecular mechanism in the selective depletion of liver CSCs.

Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine.

Fibroblast activation proteins (FAP) are overexpressed in the tumor stroma and have received attention as target molecules for radionuclide therapy. The FAP inhibitor (FAPI) is used as a probe to deliver nuclides to cancer tissues. In this study, we designed and synthesized four novel At-FAPI(s) possessing polyethylene glycol (PEG) linkers between the FAP-targeting and At-attaching moieties.

Fibroblast Activation Protein Inhibitor Theranostics: Preclinical Considerations.

Fibroblast activation protein (FAP) was first reported in 1986. However, FAP is not expressed in normal fibroblasts, normal or malignant epithelial cells, or the stroma of benign epithelial tumors. FAP is a cell membrane-bound serine peptidase overexpressed on the surface of cancer-associated fibroblasts and, as such, is a novel target for molecular imaging of several tumors.

Skeletal muscle atrophy is exacerbated by steatotic and fibrotic liver-derived TNF-α in senescence-accelerated mice.

Background And Aim: Although liver diseases, including non-alcoholic steatohepatitis, are associated with skeletal muscle atrophy, the mechanism behind their association has not been fully elucidated. In this study, the effects of aging and non-alcoholic steatohepatitis on the skeletal muscle, and the interaction between the liver and muscle were investigated using a diet-induced non-alcoholic steatohepatitis model in senescence-accelerated mice.

Methods: A total of four groups of senescence-accelerated mice and the control mice were fed either a non-alcoholic steatohepatitis-inducing or control diet, and their livers and skeletal muscles were removed for examinations.

Mathematical Model for Evaluation of Tumor Response in Targeted Radionuclide Therapy with At Using Implanted Mouse Tumor.

Recent introduction of alpha-emitting radionuclides in targeted radionuclide therapy has stimulated the development of new radiopharmaceuticals. Preclinical evaluation using an animal experiment with an implanted tumor model is frequently used to examine the efficiency of the treatment method and to predict the treatment response before clinical trials. Here, we propose a mathematical model for evaluation of the tumor response in an implanted tumor model and apply it to the data obtained from the previous experiment of At treatment in a thyroid cancer mouse model.

Effect to Therapy of Sodium-Iodine Symporter Expression by Alpha-Ray Therapeutic Agent via Sodium/Iodine Symporter.

This study confirmed the effect of sodium/iodine symporter (NIS) expression on existing drugs by in vitro and in vivo tests using cultured cell lines. The tumor growth inhibitory effect of sodium astatide ([At]NaAt) was evaluated by in vitro and in vivo tests using human thyroid cancer cells (K1, K1/NIS and K1/NIS-DOX). NIS expression in cancer cells was controlled using the Tet-On system.