Mutation Analysis of TMB-High Colorectal Cancer: Insights Into Molecular Pathways and Clinical Implications.

Colorectal cancer (CRC) is well characterized in terms of genetic mutations and the mechanisms by which they contribute to carcinogenesis. Mutations in APC, TP53, and KRAS are common in CRC, indicating key roles for these genes in tumor development and progression. However, for certain tumors with low frequencies of these mutations that are defined by tumor location and molecular phenotypes, a carcinogenic mechanism dependent on BRAF mutations has been proposed.

Adipsin-dependent adipocyte maturation induces cancer cell invasion in breast cancer.

Adipocyte-cancer cell interactions promote tumor development and progression. Previously, we identified adipsin (CFD) and its downstream effector, hepatocyte growth factor (HGF), as adipokines that enhance adipocyte-breast cancer stem cell interactions. Here, we show that adipsin-dependent adipocyte maturation and the subsequent upregulation of HGF promote tumor invasion in breast cancers.

B Cells of Early-life Origin Defined by RAG2-based Lymphoid Cell Tracking under Native Hematopoietic Conditions.

During the perinatal period, the immune system sets the threshold to select either response or tolerance to environmental Ags, which leads to the potential to provide a lifetime of protection and health. B-1a B cells have been demonstrated to develop during this perinatal time window, showing a unique and restricted BCR repertoire, and these cells play a major role in natural Ab secretion and immune regulation. In the current study, we developed a highly efficient temporally controllable RAG2-based lymphoid lineage cell labeling and tracking system and applied this system to understand the biological properties and contribution of B-1a cells generated at distinct developmental periods to the adult B-1a compartments.

Plant GARDEN: a portal website for cross-searching between different types of genomic and genetic resources in a wide variety of plant species.

Background: Plant genome information is fundamental to plant research and development. Along with the increase in the number of published plant genomes, there is a need for an efficient system to retrieve various kinds of genome-related information from many plant species across plant kingdoms. Various plant databases have been developed, but no public database covers both genomic and genetic resources over a wide range of plant species.

Intra-Arterial Injection of Temporary Embolic Material Through a Needle Inserted into the Radial or Ulnar Artery for Distal and Proximal Interphalangeal Joint Osteoarthritis: A Retrospective Study of 92 Patients.

Purpose: To assess the efficacy and safety of intra-arterial injection of imipenem/cilastatin sodium (IPM/CS) via a needle placed into the radial artery or ulnar artery (RA/UA) for distal interphalangeal and proximal interphalangeal joint osteoarthritis (DIP/PIP-OA).

Materials And Methods: This is a retrospective single-arm cohort study. Ninety-two patients [92% women, mean (SD) age 55(8.

Clinical application of long-read nanopore sequencing in a preimplantation genetic testing pre-clinical workup to identify the junction for complex Xq chromosome rearrangement-related disease.

Objective: Xq chromosome duplication with complex rearrangements is generally acknowledged to be associated with neurodevelopmental disorders, such as Pelizaeus-Merzbacher disease (PMD) and MECP2 duplication syndrome. For couples who required a PGT-M (pre-implantation genetic testing for monogenic disease) for these disorders, junction-specific PCR is useful to directly detect pathogenic variants. Therefore, pre-clinical workup for PGT-M requires the identification of the junction of duplicated segments in PMD and MECP2 duplication syndrome, which is generally difficult.

Estimating copy number to determine BRCA2 deletion status and to expect prognosis in localized prostate cancer.

Background: The significance of BRCA alterations has been implicated in the development of metastatic castration-resistant prostate cancer (PC). The details of the frequency and significance of BRCA alterations in localized PC remain unknown. In this study, we investigated the frequency and clinical significance of BRCA alterations in localized PCs using an in-house next-generation sequencer (NGS) system.

Depletion of R270C Mutant p53 in Osteosarcoma Attenuates Cell Growth but Does Not Prevent Invasion and Metastasis In Vivo.

Novel therapeutic targets are needed to better treat osteosarcoma, which is the most common bone malignancy. We previously developed mouse osteosarcoma cells, designated AX (accelerated bone formation) cells from bone marrow stromal cells. AX cells harbor both wild-type and mutant forms of p53 (R270C in the DNA-binding domain, which is equivalent to human R273C).

Pigment epithelium-derived factor promotes peritoneal dissemination of ovarian cancer through induction of immunosuppressive macrophages.

Peritoneal dissemination of ovarian cancer (OC) correlates with poor prognosis, but the mechanisms underlying the escape of OC cells from the intraperitoneal immune system have remained unknown. We here identify pigment epithelium-derived factor (PEDF) as a promoting factor of OC dissemination, which functions through induction of CD206 Interleukin-10 (IL-10)-producing macrophages. High PEDF gene expression in tumors is associated with poor prognosis in OC patients.

TAS-Seq is a robust and sensitive amplification method for bead-based scRNA-seq.

Single-cell RNA-sequencing (scRNA-seq) is valuable for analyzing cellular heterogeneity. Cell composition accuracy is critical for analyzing cell-cell interaction networks from scRNA-seq data. However, droplet- and plate-based scRNA-seq techniques have cell sampling bias that could affect the cell composition of scRNA-seq datasets.

Regulatory roles of fibronectin and integrin α5 in reorganization of the actin cytoskeleton and completion of adipogenesis.

Cellular differentiation is characterized by changes in cell morphology that are largely determined by actin dynamics. We previously showed that depolymerization of the actin cytoskeleton triggers the differentiation of preadipocytes into mature adipocytes as a result of inhibition of the transcriptional coactivator activity of megakaryoblastic leukemia 1 (MKL1). The extracellular matrix (ECM) influences cell morphology via interaction with integrins, and reorganization of the ECM is associated with cell differentiation.

Downregulation of Odd-Skipped Related 2, a Novel Regulator of Epithelial-Mesenchymal Transition, Enables Efficient Somatic Cell Reprogramming.

Somatic cell reprogramming proceeds through a series of events to generate induced pluripotent stem cells (iPSCs). The early stage of reprogramming of mouse embryonic fibroblasts is characterized by rapid cell proliferation and morphological changes, which are accompanied by downregulation of mesenchyme-associated genes. However, the functional relevance of their downregulation to reprogramming remains poorly defined.

Structurally-discovered KLF4 variants accelerate and stabilize reprogramming to pluripotency.

Non-genetically modified somatic cells can only be inefficiently and stochastically reprogrammed to pluripotency by exogenous expression of reprogramming factors. Low competence of natural reprogramming factors may prevent the majority of cells to successfully and synchronously reprogram. Here we screened DNA-interacting amino acid residues in the zinc-finger domain of KLF4 for enhanced reprogramming efficiency using alanine-substitution scanning methods.

Target enrichment long-read sequencing with adaptive sampling can determine the structure of the small supernumerary marker chromosomes.

Structural analysis of small supernumerary marker chromosomes (sSMCs) has revealed that many have complex structures. Structural analysis of sSMCs by whole genome sequencing using short-read sequencers is challenging however because most present with a low level of mosaicism and consist of a small region of the involved chromosome. In this present study, we applied adaptive sampling using nanopore long-read sequencing technology to enrich the target region and thereby attempted to determine the structure of two sSMCs with complex structural rearrangements previously revealed by cytogenetic microarray.

Early reactivation of clustered genes on the inactive X chromosome during somatic cell reprogramming.

Reprogramming of murine female somatic cells to induced pluripotent stem cells (iPSCs) is accompanied by X chromosome reactivation (XCR), by which the inactive X chromosome (Xi) in female somatic cells becomes reactivated. However, how Xi initiates reactivation during reprogramming remains poorly defined. Here, we used a Sendai virus-based reprogramming system to generate partially reprogrammed iPSCs that appear to be undergoing the initial phase of XCR.

Transcatheter Arterial Embolization Using Imipenem/Cilastatin Sodium for Chronic Low Back Pain Resistant to Conservative Treatment: A Pilot Study with 2-Year Follow-Up.

Purpose: To evaluate the safety and 2-year follow-up clinical outcomes of transcatheter arterial embolization (TAE) using imipenem/cilastatin sodium for chronic low back pain resistant to conservative treatment.

Materials And Methods: A retrospective review identified 14 patients who underwent TAE for chronic low back pain between October 2017 and August 2018. Patients with low back pain related to the facet or sacroiliac joint, lasting ≥ 6 months, refractory to ≥ 3 months of conservative treatment were eligible for TAE.

Intra-arterial Infusion of Temporary Embolic Material in a Patient with Plantar Fasciitis: A Case Report.

This case report concerns a 51-year-old woman with a 6-month history of severe right heel pain diagnosed as plantar fasciitis (PF) treated with intra-arterial infusion of imipenem/cilastatin (IPM/CS) through a 24G indwelling needle directly inserted into the posterior tibial artery (PTA). Angiography of the indwelling needle immediately before the infusion of IPM/CS demonstrated an increased number of abnormal vessels at the calcaneal attachment of the plantar fascia. Two procedures were planned: The first procedure was performed, and the second was performed 1 month after the first.

Molecular classification and diagnostics of upper urinary tract urothelial carcinoma.

Upper urinary tract urothelial carcinoma (UTUC) is one of the common urothelial cancers. Its molecular pathogenesis, however, is poorly understood, with no useful biomarkers available for accurate diagnosis and molecular classification. Through an integrated genetic study involving 199 UTUC samples, we delineate the landscape of genetic alterations in UTUC enabling genetic/molecular classification.