PRRX1 is a master transcription factor of stromal fibroblasts for myofibroblastic lineage progression.

Although stromal fibroblasts play a critical role in cancer progression, their identities remain unclear as they exhibit high heterogeneity and plasticity. Here, a master transcription factor (mTF) constructing core-regulatory circuitry, PRRX1, which determines the fibroblast lineage with a myofibroblastic phenotype, is identified for the fibroblast subgroup. PRRX1 orchestrates the functional drift of fibroblasts into myofibroblastic phenotype via TGF-β signaling by remodeling a super-enhancer landscape.

Perspectives and advances in probiotics and the gut microbiome in companion animals.

As the number of households that raise dogs and cats is increasing, there is growing interest in animal health. The gut plays an important role in animal health. In particular, the microbiome in the gut is known to affect both the absorption and metabolism of nutrients and the protective functions of the host.

Validation of ZMYND8 as a new treatment target in hepatocellular carcinoma.

Background: ZMYND8 (Zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8) has been known to play an important role in tumor regulation in various types of cancer. However, the results of ZMYND8 expression and their clinical significance in hepatocellular carcinoma (HCC) have not yet been published. In the present study, we investigate the expression of ZMYND8 protein and mRNA in HCC and elucidate its prognostic significance.

Validation of ORAOV1 as a new treatment target in hepatocellular carcinoma.

Purpose: Chromosome 11q13.2, which contains genes cyclin D1 (CCND1), fibroblast growth factor 19 (FGF19), and Oral Cancer Overexpressed 1 (ORAOV1), is the most highly amplified peak in hepatocellular carcinoma (HCC). CCND1 and FGF19 have been already suggested as therapeutic targets of HCC, but the role of ORAOV1 in carcinogenesis of HCCs has not been reported.

New screening system using Twist1 promoter activity identifies dihydrorotenone as a potent drug targeting cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAFs) are the most abundant stromal cells in tumor microenvironments. These cells strongly support tumor progression and are considered to be potent therapeutic targets. Therefore, drugs targeting CAFs have been developed, but most of them have failed in clinical trials.

Ubiquitin-Specific Protease 21 Promotes Colorectal Cancer Metastasis by Acting as a Fra-1 Deubiquitinase.

Fos-related-antigen-1 (Fra-1), a member of the activator protein-1 (AP-1) transcription factor superfamily, has an essential role in cancer progress and metastasis and Fra-1 is considered a therapeutic target in metastatic cancer including metastatic colorectal cancer (mCRC). However, its regulation at protein level has not yet been clearly elucidated. We found that ubiquitin-specific protease 21 (USP21) increases Fra-1 stability by deubiquitinating Fra-1 and enhances the expression of Fra-1 target genes in colon cancer cells.

A positive feedback loop bi-stably activates fibroblasts.

Although fibroblasts are dormant in normal tissue, they exhibit explosive activation during wound healing and perpetual activation in pathologic fibrosis and cancer stroma. The key regulatory network controlling these fibroblast dynamics is still unknown. Here, we report that Twist1, a key regulator of cancer-associated fibroblasts, directly upregulates Prrx1, which, in turn, increases the expression of Tenascin-C (TNC).

Drug repurposing screening identifies bortezomib and panobinostat as drugs targeting cancer associated fibroblasts (CAFs) by synergistic induction of apoptosis.

Cancer associated fibroblasts (CAFs) are the most abundant components of cancer-microenvironment. They play important roles in cancer initiation, progression, and metastasis. In addition, CAFs can confer drug-resistance to cancer cells.

Highly Sensitive Flexible Pressure Sensors Based on Printed Organic Transistors with Centro-Apically Self-Organized Organic Semiconductor Microstructures.

A highly sensitive pressure sensor based on printed organic transistors with three-dimensionally self-organized organic semiconductor microstructures (3D OSCs) was demonstrated. A unique organic transistor with semiconductor channels positioned at the highest summit of printed cylindrical microstructures was achieved simply by printing an organic semiconductor and polymer blend on the plastic substrate without the use of additional etching or replication processes. A combination of the printed organic semiconductor microstructure and an elastomeric top-gate dielectric resulted in a highly sensitive organic field-effect transistor (FET) pressure sensor with a high pressure sensitivity of 1.

Twist1 is highly expressed in cancer-associated fibroblasts of esophageal squamous cell carcinoma with a prognostic significance.

Cancer-associated fibroblasts (CAFs) play important roles in cancer progression. Twist1 was recently reported to be a key regulator of CAFs in gastric cancer, but its role in other types of cancer remains unclear, especially for esophageal squamous cell carcinoma (ESCC). We assessed the Twist1 expression on stromal fibroblasts using immunohistochemistry in 169 tissue specimens from ESCC patients, and performed and experiments to confirm the role of Twist1 in CAFs of ESCC.

Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma.

Background: Tenascin-C, an adhesion modulatory extracellular matrix molecule, is highly expressed in numerous human malignancies; thus, it may contribute to carcinogenesis and tumor progression. We explored the clinicopathological significance of Tenascin-C as a prognostic determinant of esophageal squamous cell carcinoma (ESCC).

Methods: In ESCC patient tissues and cell lines, the presence of isoforms were examined using western blotting.

Centro-Apical Self-Organization of Organic Semiconductors in a Line-Printed Organic Semiconductor: Polymer Blend for One-Step Printing Fabrication of Organic Field-Effect Transistors.

Here we report the first demonstration for centro-apical self-organization of organic semiconductors in a line-printed organic semiconductor: polymer blend. Key feature of this work is that organic semiconductor molecules were vertically segregated on top of the polymer phase and simultaneously crystallized at the center of the printed line pattern after solvent evaporation without an additive process. The thickness and width of the centro-apically segregated organic semiconductor crystalline stripe in the printed blend pattern were controlled by varying the relative content of the organic semiconductors, printing speed, and solution concentrations.

High-concentration boron doping of graphene nanoplatelets by simple thermal annealing and their supercapacitive properties.

For the utilization of graphene in various energy storage and conversion applications, it must be synthesized in bulk with reliable and controllable electrical properties. Although nitrogen-doped graphene shows a high doping efficiency, its electrical properties can be easily affected by oxygen and water impurities from the environment. We here report that boron-doped graphene nanoplatelets with desirable electrical properties can be prepared by the simultaneous reduction and boron-doping of graphene oxide (GO) at a high annealing temperature.

ZNF282 (Zinc finger protein 282), a novel E2F1 co-activator, promotes esophageal squamous cell carcinoma.

Zinc finger protein 282 (ZNF282) is a newly identified transcription factor and little is known about its expression and function. Originally, ZNF282 is known to bind U5RE (U5 repressive element) of HLTV-1 (human T cell leukemia virus type 1) with a repressive effect. Recently we reported that ZNF282 functions as an estrogen receptor co-activator and plays an essential role in breast tumorigenesis.

Twist1 is a key regulator of cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAF) are key contributors to malignant progression, but their critical regulators remain largely unknown. In this study, we examined the role of Twist1, a central regulator of epithelial-mesenchymal transition in carcinoma cells, in the transdifferentiation of normal quiescent fibroblasts to CAF and we defined its upstream controls and downstream effectors. Primary human gastric fibroblast and CAF cultures were established from gastrectomy specimens and validated as nontumor cells by somatic mutation analyses.

The prognostic significance of cancer-associated fibroblasts in esophageal squamous cell carcinoma.

Background: Cancer-associated fibroblasts (CAF) are activated fibroblasts in the cancer stroma and play an important role in cancer progression. Some reports have indicated the correlation between the expression of CAF markers and adverse prognosis in several cancers. However, no reports have studied CAF phenotype and its clinical relevance in esophageal squamous cell carcinoma (ESCC).