Clinical significance of MET in gastric cancer

Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC. Hepatocyte growth factor and its receptor, c-MET (MET), play key roles in tumor growth through activated signaling pathways from receptor in GC cells. Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC. Preclinical studies in animal models have shown that MET antibodies or small-molecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells. These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC.     

Genetic heterogeneity of uncharacterized childhood autoimmune diseases with lymphoproliferation

Autoimmune diseases in children are rare and can be difficult to diagnose.  Single causative genes have been identified for some pediatric autoimmune diseases. Such orphan diseases may not be diagnosed properly due to the variability of patients' phenotypes. Guidelines for the diagnostic process need to be developed. Fifteen patients with uncharacterized childhood autoimmune diseases with lymphoproliferation that had negative testing for autoimmune lymphoproliferative syndrome were subjected to whole‐exome sequencing to identify genes associated with these conditions. Five causative genes, CTLA4, STAT3, TNFAIP3, IKZF1, and PSTPIP1, were identified. These genes should be considered as candidates for uncharacterized childhood autoimmune diseases with lymphoproliferation.     

A nasal vaccine comprising B-subunit derivative of Shiga toxin 2 for cross-protection against Shiga toxin types 1 and 2

Enterohemorrhagic Escherichia coli (EHEC) produces Stx1 and Stx2 causing severe diseases. Their B-subunits (StxBs) exhibit low immunogenicity and the anti-StxB antibodies neutralizing both Stxs has not been prepared yet. By intranasal vaccination with His-tagged-StxB (Stx1B-His or Stx2B-His) plus a mutant heat-labile enterotoxin (mLT) in mice, their serum and lung fluid reacted with appropriate StxB. Mice vaccinated with Stx2B-His plus mLT had antibodies reacting Stx1B and showed the resistance to toxemia of Stx1 and Stx2. This is the first demonstration to get anti-Stx2B serum neutralizing both Stxs. These suggest that the nasal vaccination with Stx2B-His and mLT is effective for preventing toxemias by EHEC.     

Comparison of the health condition between the 8020 achievers and the 8020 non-achievers

AIM: To review of the difference in the health condition between 8020 achievers and 8020 non-achievers covering 25 papers which were published mainly in Japan. BACKGROUND: A campaign targeting the elderly to retain at least 20 teeth by the time they reach the age of 80 years (8020) has been in place since 1991 in Japan. RESULTS: The percentage of 8020 achievers increased from 10.9% in 1993, 15.3% in 1999 and 24.1% in 2005. The 8020 achievers had a tendency towards a strict upbringing and were not fond of sweets in their childhood. Physical indices such as height, weight, BMI score, bone mineral density, balance ability, grip strength, and exercise function in the 8020 achievers were better than the 8020 non-achievers. A close inverse relationship between the number of teeth and heart rate was recognised. The food intake survey showed that 8020 achievers ate many kinds of food. However, these foods were those with less kilocalories and lower levels of carbohydrate. The 8020 achievers had good activity in daily life (ADL) level, were satisfied with life, and had a higher cumulative survival rate. Oral health conditions including periodontal condition, masticatory ability, occlusal force, occlusal and maxillofacial forms in the 8020 achievers were better than the 8020 non-achievers.