Extrachromosomal DNA dynamics contribute to intratumoural receptor tyrosine kinase genetic heterogeneity and drug resistance in gastric cancer.

Chromosomal instability in gastric cancer cells is associated with the amplification of oncogenes that encode receptor tyrosine kinases (RTKs), such as HER2 and FGFR2; such gene amplification varies from cell to cell and manifests as genetic heterogeneity within tumours. The intratumoural genetic heterogeneity of RTK gene amplification causes heterogeneity in RTK protein expression, which has been suggested to be associated with therapeutic resistance to RTK inhibitors; however, the underlying mechanism is not fully understood. Here, we show that extrachromosomal DNA (ecDNA) causes intratumoural genetic heterogeneity in RTKs and drug resistance due to diverse dynamic changes.

Cancer-related gene mutations and intratumoral genetic heterogeneity in human epidermal growth factor receptor 2 heterogeneous gastric cancer.

Human epidermal growth factor receptor 2 (HER2) protein overexpression is associated with HER2 gene amplification, a critical driver oncogenetic change in gastric cancer. HER2 heterogeneity in advanced gastric cancer is associated with a poor prognosis and affects the clinical efficacy of trastuzumab. However, the mechanisms of HER2 heterogeneity are not fully understood.

Antifibrotic Agent Pirfenidone Suppresses Proliferation of Human Pancreatic Cancer Cells by Inducing G0/G1 Cell Cycle Arrest.

Background: Pirfenidone (PFD), which is an antifibrotic agent used for treatment of idiopathic pulmonary fibrosis, induces G0/G1 cell cycle arrest in fibroblasts. We hypothesized that PFD-induced G0/G1 cell cycle arrest might be achieved in other types of cells, including cancer cells. Here we investigated the effects of PFD on the proliferation of pancreatic cancer cells (PCCs) in vitro.

Association of HER2 gene amplification and tumor progression in early gastric cancer.

Overexpression of human epidermal growth factor receptor 2 (HER2) protein in association with HER2 gene amplification is found in 7-34% of gastric cancers. In breast cancer, HER2 overexpression is a prognostic factor in advanced cases and is associated with tumor progression in ductal carcinoma in situ. However, the biological and clinical significance of HER2 status in early gastric cancer is unknown.

Red Blood Cell-Shaped Microparticles with a Red Blood Cell Membrane Demonstrate Prolonged Circulation Time in Blood.

Prolonging the circulation time (CT) of microparticles (MPs) in the blood is key for a successful microparticle-based medicinal approach to serve as drug delivery systems (DDSs). Previously, we reported that MPs that mimic the shape of red blood cells (RBCs) avoid accumulation in the spleen and lungs. We now describe the effectiveness of mimicking not only the shape of RBCs but also their surface structure for the prolongation of CT.

Acute brainstem compression by intratumoral hemorrhages in an intracranial hypoglossal schwannoma.

A 77-year-old female in the hospital was found tachycardic and hypothermic by a nurse, and the patient's respiration subsequently ceased. Forensic autopsy revealed an intracranial cystic tumor that would have compressed the brainstem. On microscopic examination, the tumor was diagnosed as an Antoni A schwannoma growth, and recent multiple intratumoral hemorrhages in the intracranial schwannoma were observed, suggesting the sudden enlargement of the intracranial schwannoma due to intratumoral hemorrhaging.

Molecular-biological analysis of acute lung injury (ALI) induced by heat exposure and/or intravenous administration of oleic acid.

The aim of this study was to molecular-biologically investigate the interaction between heat exposure and pulmonary fat embolization in regards to the development of acute lung injury (ALI). Ten-week-old Wistar male rats were divided into four groups: (1) oleic acid injected into caudal vein after heat exposure, (2) oleic acid injected without heat exposure, (3) soybean oil injected after heat exposure, and (4) soybean oil injected without heat exposure, and then mRNA expression of eight inflammatory mediators related to ALI/acute respiratory distress syndrome (ARDS) and heat shock protein 70 (Hsp70) in lung was determined 1h after the injection. mRNA expression of interleukin 1 beta (Il1b), tumor necrosis factor alpha (Tnfa), vascular endothelial growth factor A (Vegfa), transforming growth factor beta 1 (Tgfb1) and Hsp70 was significantly increased by heat exposure, while that of Il1b, interleukin 6 (Il6), Tnfa, macrophage inflammatory protein 2 (Mip2) and granulocyte macrophage-colony stimulating factor (Gm-csf) was significantly elevated by the injection of oleic acid.