GET4 is a novel driver gene in colorectal cancer that regulates the localization of BAG6, a nucleocytoplasmic shuttling protein

Colorectal cancer (CRC) is one of the most common types of cancer and a significant cause of cancer mortality worldwide. Further improvements of CRC therapeutic approaches are needed. BCL2‐associated athanogene 6 (BAG6), a multifunctional scaffold protein, plays an important role in tumor progression. However, regulation of BAG6 in malignancies remains unclear. This study showed that guided entry of tail‐anchored proteins factor 4 (GET4), a component of the BAG6 complex, regulates the intercellular localization of BAG6 in CRC. Furthermore, GET4 was identified as a candidate driver gene on the short arm of chromosome 7, which is often amplified in CRC, by our bioinformatics approach using the CRC dataset from The Cancer Genome Atlas. Clinicopathologic and prognostic analyses using CRC datasets showed that GET4 was overexpressed in tumor cells due to an increased DNA copy number. High GET4 expression was an independent poor prognostic factor in CRC, whereas BAG6 was mainly overexpressed in the cytoplasm of tumor cells without gene alteration. The biological significance of GET4 was examined using GET4 KO CRC cells generated with CRISPR‐Cas9 technology or transfected CRC cells. In vitro and in vivo analyses showed that GET4 promoted tumor growth. It appears to facilitate cell cycle progression by cytoplasmic enrichment of BAG6‐mediated p53 acetylation followed by reduced p21 expression. In conclusion, we showed that GET4 is a novel driver gene and a prognostic biomarker that promotes CRC progression by inducing the cytoplasmic transport of BAG6. GET4 could be a promising therapeutic molecular target in CRC.     

IgA Vasculitis in an Oldest-old Patient Successfully Treated with Glucocorticoid

A 94-year-old man was diagnosed with immunoglobulin A vasculitis (IgAV), and losartan was initiated. His renal function rapidly deteriorated over a month; therefore, methylprednisolone was administered intravenously for three days followed by oral prednisolone. Renal function improvement and both proteinuria and hematuria remission were observed within six months. Prednisolone tapering was completed at eight months. In this case, we monitored the patient carefully and started glucocorticoids as soon as the patient''s renal function deteriorated. We were thus able to treat the patient with a relatively small dose of glucocorticoids in a short treatment period without any adverse events due to glucocorticoids.     

The wound/burn guidelines – 6: Guidelines for the management of burns

Burns are a common type of skin injury encountered at all levels of medical facilities from private clinics to core hospitals. Minor burns heal by topical treatment alone, but moderate to severe burns require systemic management, and skin grafting is often necessary also for topical treatment. Inappropriate initial treatment or delay of initial treatment may exert adverse effects on the subsequent treatment and course. Therefore, accurate evaluation of the severity and initiation of appropriate treatment are necessary. The Guidelines for the Management of Burn Injuries were issued in March 2009 from the Japanese Society for Burn Injuries as guidelines concerning burns, but they were focused on the treatment for extensive and severe burns in the acute period. Therefore, we prepared guidelines intended to support the appropriate diagnosis and initial treatment for patients with burns that are commonly encountered including minor as well as moderate and severe cases. Because of this intention of the present guidelines, there is no recommendation of individual surgical procedures.     

Combined association of oral and skeletal muscle health with type 2 diabetes mellitus among community-dwelling older adults in Japan: a cross-sectional study

Objective: Although oral health and skeletal muscle status are known to be risk factors for type 2 diabetes mellitus (T2DM), there is limited information on their combined effects among community-dwelling older adults. The purpose of this study was to investigate the association between oral health and skeletal muscle status among older adults with T2DM in Japan.Participants and Methods: This cross-sectional study included data from individuals aged ≥60 years. T2DM was defined as a glycosylated hemoglobin A1c level ≥48 mmol/mol (≥6.5%) or the use of hypoglycemic agents. For oral health status, dental hygienists assessed the number of teeth (NT) and masticatory function (MF). Skeletal muscle status was assessed using skeletal muscle mass index (SMI) and handgrip strength (HGS). Logistic regression analysis examined T2DM in nine-category combinations of oral health status (each of the three categories in NT and MF) and skeletal status (each of the three categories in SMI and HGS).Results: T2DM was prevalent in 83 participants (16.4%) and was significantly associated with low NT and SMI (odds ratio [OR] = 5.93, 95% confidence interval [CI]: 1.37–25.73) and low MF and SMI (OR = 4.48, 95% CI: 1.23–16.35) compared to high NT and SMI and high MF and SMI, respectively.Conclusion: Our findings indicate that low muscle mass with tooth loss or masticatory dysfunction is associated with T2DM among community-dwelling older adults. This suggests that maintaining oral health and muscle mass may be an effective strategy for the prevention of T2DM.     

Light chain cardiac amyloidosis in a nonagenarian

Cardiac amyloidosis is an infiltrative and restrictive cardiomyopathy caused by the extracellular deposition of amyloid fib-rils within the heart as systemic amyloidosis,lead-ing to heart failure,reduced quality of life,and death.[1]There are two major amyloid fibril proteins that af-fect the heart:amyloid immunoglobulin light chain(AL)and amyloid transthyretin(ATTR).The latter is further subdivided into wild-type ATTR and variant types based on the presence of a mutation in the transthyretin gene.     

Muir-Torre syndrome caused by exonic deletion of <Emphasis Type="Italic">MLH1</Emphasis> due to homologous recombination

Background

Muir-Torre syndrome (MTS) is characterized by sebaceous neoplasms with internal malignancies and regarded as a variant of hereditary nonpolyposis colorectal cancer (HNPCC). Pathogenic variations of MTS have been identified in the MSH2, MLH1, and MSH6 genes, with the majority of variations located in MSH2.

Objectives

To present an MTS patient who was the only individual with skin malignancies within a cancer-prone pedigree and to showthe usefulness ofRNA-based genetic analysis in the investigation of MTS.

Materials & methods

A 77-year-old man who had operated X-ray equipment at his workplace in his twenties was clinically diagnosed with MTS and investigated by RNA-based analysis, multiplex ligation-dependent probe amplification, and genomic DNA sequencing.

Results

The patient had suffered from sebaceous tumours, squamous cell carcinomas of the skin, and colon cancer. The patient’s family history was remarkable for visceral malignant diseases. Genetic analysis revealed homologous recombination between two Alu elements within intron 4 and 5 of the MLH1 gene. The rearrangement caused a 1,222-bp deletion, including the entire exon 5. Deletion of exon 5 has previously been reported only in two patients with HNPCC, and not in patients with MTS.

Conclusions

For the genetic analysis of MTS, the possibility of rare copy number variations of MLH1, as well as MSH2 variations, should be considered. RNA-based screening using puromycin is recommended in order to identify such variations. It remains unclear why only the proband among the pedigree had skin malignancies, however, the skin carcinogenesis might have been related to occupational radiation exposure.