Generation of Monosomy 21q Human iPS Cells by CRISPR/Cas9-Mediated Interstitial Megabase Deletion.

Missing an entire chromosome or chromosome arm in normal diploid cells has a deleterious impact on cell viability, which may contribute to the development of specific birth defects. Nevertheless, the effects of chromosome loss in human cells have remained unexplored due to the lack of suitable model systems. Here, we developed an efficient, selection-free approach to generate partial monosomy in human induced pluripotent stem cells (iPSCs).

AMIGO2 is involved in the spread of peritoneal metastasis in serous ovarian cancer via promoting adhesion to the peritoneal mesothelial cells.

Background: Amphoterin-induced gene and open reading frame 2 (AMIGO2) have been reported to be related to the prognosis of colorectal, gastric, and cervical cancer. However, their association with ovarian cancer remains unclear. This study aimed to elucidate the role of AMIGO2 in ovarian cancer.

Exosomal miR-493 suppresses MAD2L1 and induces chemoresistance to intraperitoneal paclitaxel therapy in gastric cancer patients with peritoneal metastasis.

Intraperitoneal (IP) chemotherapy with paclitaxel (PTX) for gastric cancer (GC) with peritoneal metastasis (PM) is considered a promising treatment approach, however, there are no useful biomarkers to predict the efficacy of IP therapy. We examined the association between intra-peritoneal exosomes, particularly exosomal micro-RNAs (exo-miRNAs), and IP-chemo sensitivity. MKN45 cells that were cultured with intra-peritoneal exosomes from patients who did not respond to IP therapy with PTX (IP group) exhibited resistance to PTX compared with exosomes from responding patients (IP group) (p = 0.

Increased chemokine ligand 26 expression and its involvement in epithelial-mesenchymal transition in the endometrium with adenomyosis.

Objective: Adenomyosis is a gynecologic disorder characterized by symptoms of dysmenorrhea, abnormal uterine bleeding, and infertility. This study aimed to analyze the expression profiles of key inflammatory cytokines in the endometrium with adenomyosis and their involvement in epithelial-mesenchymal transition (EMT).

Study Design: Endometrial tissues collected from premenopausal women with (n = 3) or without (n = 3) adenomyosis during the secretory phase were subjected to DNA array analysis to examine inflammatory cytokines.

AMIGO2 expression as a predictor of recurrence in cervical cancer with intermediate risk.

Patients with recurrent cervical cancer have limited treatment options and are often considered to be incurable. Since the expression of amphoterin-induced gene and open reading frame 2 (AMIGO2) in clinical samples is a prognostic factor for colorectal cancer and gastric cancer, the present aimed to elucidate whether it is also a prognostic factor for cervical cancer. Patients with primary cervical cancer who underwent radical hysterectomy or radical trachelectomy at our institution (Faculty of Medicine, Tottori University, Yonago, Japan) between September 2005 and October 2016 were retrospectively collected.

Full-length human dystrophin on human artificial chromosome compensates for mouse dystrophin deficiency in a Duchenne muscular dystrophy mouse model.

Dystrophin maintains membrane integrity as a sarcolemmal protein. Dystrophin mutations lead to Duchenne muscular dystrophy, an X-linked recessive disorder. Since dystrophin is one of the largest genes consisting of 79 exons in the human genome, delivering a full-length dystrophin using virus vectors is challenging for gene therapy.

Epstein-Barr virus reactivation in peripheral B lymphocytes induces IgM-type thyrotropin receptor autoantibody production in patients with Graves' disease.

Epstein-Barr virus (EBV) is a human herpes virus that latently infects B lymphocytes. When EBV is reactivated, host B cells differentiate into plasma cells and produce IgM-dominant antibodies as well as many progeny virions. The aims of the present study were to confirm the IgM dominance of thyrotropin-receptor antibodies (TRAbs) produced by EBV reactivation and investigate the roles of TRAb-IgM in Graves' disease.

Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis.

DNA methyltransferases (DNMTs) catalyze methylation at the C5 position of cytosine with S-adenosyl-L-methionine. Methylation regulates gene expression, serving a variety of physiological and pathophysiological roles. The chemical mechanisms regulating DNMT enzymatic activity, however, are not fully elucidated.

Kidney organoid derived from renal tissue stem cells is a useful tool for histopathological assessment of nephrotoxicity in a cisplatin-induced acute renal tubular injury model.

Organoids derived from renal tissue stem cells (KS cells) isolated from the S3 segment of adult rat nephrons have previously been developed and evaluated. However, data regarding the histopathological evaluation of these organoids are limited. Therefore, in this study, we performed histopathological examinations of the properties of these organoids and evaluated the nephrotoxicity changes induced by cisplatin treatment.

Liver Metastasis Formation Is Defined by AMIGO2 Expression via Adhesion to Hepatic Endothelial Cells in Human Gastric and Colorectal Cancer Cells.

The adhesion of circulating cancer cells to vascular endothelial cells is an initial and critical step in distant metastases. Amphoterin-induced gene and open reading frame 2 (AMIGO2) was found to regulate tumor cell adhesion to hepatic endothelial cells and act as a driver gene for liver metastasis in mouse cell lines. However, whether the role of AMIGO2 observed in mouse tumor cells can be extrapolated to human cancer cells in vivo has not been verified.

The impact of AMIGO2 on prognosis and hepatic metastasis in gastric cancer patients.

Background: Gastric cancer (GC) is one of the most common malignancies, and the liver is the most common site of hematogenous metastasis of GC. AMIGO2 is a type I transmembrane protein that has been implicated in tumour cell adhesion in adenocarcinomas; however, its importance in GC remains undetermined.

Methods: We analyzed AMIGO2 expression by immunohistochemistry using the specific monoclonal antibody for human AMIGO2 in 128 patients who underwent GC surgery to evaluate its relationship between various metastatic and clinical outcomes in GC.

Panel of human cell lines with human/mouse artificial chromosomes.

Human artificial chromosomes (HACs) and mouse artificial chromosomes (MACs) are non-integrating chromosomal gene delivery vectors for molecular biology research. Recently, microcell-mediated chromosome transfer (MMCT) of HACs/MACs has been achieved in various human cells that include human immortalised mesenchymal stem cells (hiMSCs) and human induced pluripotent stem cells (hiPSCs). However, the conventional strategy of gene introduction with HACs/MACs requires laborious and time-consuming stepwise isolation of clones for gene loading into HACs/MACs in donor cell lines (CHO and A9) and then transferring the HAC/MAC into cells via MMCT.

Establishment of an antibody specific for AMIGO2 improves immunohistochemical evaluation of liver metastases and clinical outcomes in patients with colorectal cancer.

Instruction: The human amphoterin-induced gene and open reading frame (AMIGO) was identified as a novel cell adhesion molecule of type I transmembrane protein. AMIGO2 is one of three members of the AMIGO family (AMIGO1, 2, and 3), and the similarity between them is approximately 40% at the amino acid level. We have previously shown that AMIGO2 functions as a driver of liver metastasis.

AMIGO2 contained in cancer cell-derived extracellular vesicles enhances the adhesion of liver endothelial cells to cancer cells.

Adhesion of cancer cells to vascular endothelial cells in target organs is an initial step in cancer metastasis. Our previous studies revealed that amphoterin-induced gene and open reading frame 2 (AMIGO2) promotes the adhesion of tumor cells to liver endothelial cells, followed by the formation of liver metastasis in a mouse model. However, the precise mechanism underlying AMIGO2-promoted the adhesion of tumor cells and liver endothelial cells remains unknown.

Newly Invented Micellized Vitamin K2 Recovered Prolonged Prothrombin Time under Obstructive Jaundice in Rats with Bile Duct Ligation.

In cholestatic liver diseases, coagulopathy is induced by malabsorption of vitamin K. Supplementation of vitamin K has previously been shown to prevent coagulopathy. In this study, we tested the efficacy of a newly invented micellized vitamin K2 (m-vitK2) in treating coagulopathy, using a rat bile duct ligation (BDL) model.

AMIGO2 as a novel indicator of liver metastasis in patients with colorectal cancer.

Our previous study showed that adhesion molecule with immunoglobulin like domain 2 (AMIGO2) is a pivotal driver gene of liver metastasis via regulating tumor cell adhesion to liver endothelial cells in mouse models. The aim of the present study was to clarify the role of AMIGO2 in liver metastasis in patients the colorectal cancer (CRC). Two human CRC cell lines, Caco-2 (AMIGO2-low) and HCT116 (AMIGO2-high), were used in this study.

Inflammation-Related Carcinogenesis: Lessons from Animal Models to Clinical Aspects.

Inflammation-related carcinogenesis has long been known as one of the carcinogenesis patterns in humans. Common carcinogenic factors are inflammation caused by infection with pathogens or the uptake of foreign substances from the environment into the body. Inflammation-related carcinogenesis as a cause for cancer-related death worldwide accounts for approximately 20%, and the incidence varies widely by continent, country, and even region of the country and can be affected by economic status or development.

Engineering of human induced pluripotent stem cells via human artificial chromosome vectors for cell therapy and disease modeling.

Genetic engineering of induced pluripotent stem cells (iPSCs) holds great promise for gene and cell therapy as well as drug discovery. However, there are potential concerns regarding the safety and control of gene expression using conventional vectors such as viruses and plasmids. Although human artificial chromosome (HAC) vectors have several advantages as a gene delivery vector, including stable episomal maintenance and the ability to carry large gene inserts, the full potential of HAC transfer into iPSCs still needs to be explored.

Splice variants of lysosome‑associated membrane proteins 2A and 2B are involved in sunitinib resistance in human renal cell carcinoma cells.

Sunitinib, a tyrosine kinase inhibitor, is among the first‑line treatments for metastatic or advanced stage renal cell carcinoma (RCC). However, patients with RCC develop resistance to sunitinib. We have previously demonstrated that lysosome‑associated membrane protein 2 (LAMP‑2), which has three splice variants with different functions (LAMP‑2A, LAMP‑2B, and LAMP‑2C), is involved in RCC.

Real-time fluorometric evaluation of hepatoblast proliferation in vivo and in vitro using the expression of CYP3A7 coding for human fetus-specific P450.

The fields of drug discovery and regenerative medicine require large numbers of adult human primary hepatocytes. For this purpose, it is desirable to use hepatocyte-like cells (HLCs) differentiated from human pluripotent stem cells (PSCs). Premature hepatoblast-like cells (HB-LCs) differentiated from PSCs provide an intermediate source and steady supply of newly mature HLCs.