Abstract An 80-year-old woman with a history of endoscopic balloon dilation for esophageal stricture caused by accidental ingestion of caustic soda during infancy presented with dysphagia. Upper gastrointestinal endoscopy revealed a 10-cm-long, highly white, elevated lesion with a feathered appearance. This lesion was determined to be the cause of dysphagia and was completely resected via endoscopic submucosal dissection. Histopathological examination revealed a thick keratin layer on the surface of the stratified squamous epithelium, with a prominent granular layer underneath and some areas showing nuclear atypia. The lesion was diagnosed as a well-differentiated squamous cell carcinoma, pT1a-LPM, derived from epidermoid metaplasia. Cancer genome analysis revealed mutations in TP53 as well as amplification of MYC , FGFR1 , chromosome 7, and chromosome 20q. This case suggests that epidermoid metaplasia caused by chronic irritation from an esophageal stricture may have been exacerbated by the dilation procedure.
MHC class I polypeptide-related chain A (MICA) molecule is induced in response to viral infection and various types of stress. We recently reported that a single nucleotide polymorphism (SNP) rs2596542 located in the MICA promoter region was significantly associated with the risk for hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) and also with serum levels of soluble MICA (sMICA). In this study, we focused on the possible involvement of MICA in liver carcinogenesis related to hepatitis B virus (HBV) infection and examined correlation between the MICA polymorphism and the serum sMICA levels in HBV-induced HCC patients. The genetic association analysis revealed a nominal association with an SNP rs2596542; a G allele was considered to increase the risk of HBV-induced HCC (P = 0.029 with odds ratio of 1.19). We also found a significant elevation of sMICA in HBV-induced HCC cases. Moreover, a G allele of SNP rs2596542 was significantly associated with increased sMICA levels (P = 0.009). Interestingly, HCC patients with the high serum level of sMICA (>5 pg/ml) exhibited poorer prognosis than those with the low serum level of sMICA (≤5 pg/ml) (P = 0.008). Thus, our results highlight the importance of MICA genetic variations and the significance of sMICA as a predictive biomarker for HBV-induced HCC.
threo-4, 4, 4-Trichlorothreonine was synthesized completely stereoselectively through trans-4-alkoxycarbonyl-5-trichloromethyl-2-oxazoline, which was prepared almost quantitatively by the reaction of 2-isocyano acetate with chloral in the presence of an organic base. Several derivatives of these compounds were also synthesized. Furthermore, the stereochemistry of the resulting trichlorocompounds was chemically elucidated. The trichlorothreonine was easily converted into threo-threonine by hydrogenation over Pd/C in the presence of NaHCO3.
Understanding the molecular changes in tumors in response to anti‐VEGF chemotherapy is crucial for optimization of the treatment strategy for metastatic colorectal cancer. We prospectively investigated changes in the amount and constitution of circulating tumor DNA (ctDNA) in serial peripheral blood samples during chemotherapy. Sixty‐one plasma samples taken at different time points (baseline, remission, and post‐progression) and pre‐treatment tumor samples were collected from 21 patients who received bevacizumab‐containing first‐line chemotherapy. Extracted DNA was sequenced by next‐generation sequencing using a panel of 90 oncogenes. Candidate ctDNAs in plasma were validated using mutational data from matching tumors. ctDNAs encoding one to six trunk mutations were found in all 21 cases, and the mutant allele frequency (MAF) was distributed over a wide range (1‐89%). Significant decreases in the MAF at remission and increases in the MAF after progression were observed ( p < 0.001). Reduction in the MAF to below 2% in the remission period was strongly associated with better survival (16.6 vs. 32.5 months, p < 0.001). In two cases, mutations (in CREBBP and FBXW7 genes) were newly detected in ctDNA at a low frequency of around 1% in the post‐progression period. The use of ctDNA allows elucidation of the tumor clonal repertoire and tumor evolution during anti‐VEGF chemotherapy. Changes in ctDNA levels could be useful as predictive biomarkers for survival. Mutations newly detected in ctDNA in the late treatment period might reveal the rise of a minor tumor clone that may show resistance to anti‐VEGF therapy.
With the increasing use of capsule endoscopy (CE), screening tests for the small bowel can be performed with minimal invasiveness. However, occasionally, the entire small bowel cannot be observed because of decreased peristalsis of the stomach. For such cases, we perform delivery of CE by an endoscope. We retrospectively examined the usefulness of the endoscopic delivery method using a retrieval net for patients with CE stagnation in the stomach. From 2,270 patients who underwent small-bowel CE at Hiroshima University Hospital from January 2013 to January 2020, 29 consecutive patients (1.3% of the total number) in whom the small bowel could not be observed due to CE stagnation in the stomach at the time of the initial CE underwent the endoscopic delivery method using a retrieval net for secondary small-bowel CE. This study included 16 male (55%) and 13 female (45%) patients with a mean age of 69.2 ± 13.2 years. 11 patients (38%) had a history of gastrointestinal surgical resection. The entire small bowel could be observed in 19 patients (66%), and CE reached the terminal ileum in the remaining patients. A history of gastrointestinal surgical resection was significantly more frequent in the group where the entire small bowel could not be observed. The rate of small-bowel lesion detection was 55% (16/29). There were no adverse events associated with our endoscopic delivery method. Thus, the endoscopic delivery method using a retrieval net for patients with initial CE stagnation in the stomach may be safe and useful for the detection of small-bowel lesions.
The arene-supported cationic nickel allyl complexes serve as good catalysts for olefin hydrosilylation at room temperature. Detailed mechanistic studies based on experiments and DFT calculations support the novel mechanism, which includes the facile Si-H bond cleavage and Si-C bond formation, assisted by a non-innocent allyl ligand.
Electrical characteristics of HfO2/InGaAs metal–oxide–semiconductor (MOS) capacitors fabricated on In0.53Ga0.47As(001) surfaces with various surface reconstructions were investigated. To explore the effect of interface structure on the MOS properties, we prepared atomically-controlled Ga-, In-, and Al-rich (4×2) and As-rich (2×4) surfaces on InGaAs(001), and identified their atomic structures. The MOS capacitors fabricated on cation-rich InGaAs surfaces show a smaller capacitance–voltage frequency dispersion, suggesting that the cation-oxide-rich HfO2/InGaAs interfaces is preferable for suppressing interface-state density in the upper half band gap. It was also found that the interface containing higher-atomic-number cation has smaller frequency dispersion. We discuss the origin for the electrical improvement by the cation adsorption.
A novel large neutral amino acid transporter 1 (LAT1)-specific inhibitor, JPH203, is expected to cause cancer-specific starvation and possess anti-tumor effects; however, its anti-tumor mechanism for colorectal cancer (CRC) remains unclear. We analyzed LAT family gene expressions in public databases using UCSC Xena and evaluated LAT1 protein expression using immunohistochemistry in 154 cases of surgically resected CRC. We also evaluated mRNA expression using polymerase chain reaction in 10 CRC cell lines. Furthermore, JPH203 treatment experiments were conducted in vitro and in vivo using an allogeneic immune-responsive mouse model with abundant stroma created via the orthotopic transplantation of the mouse-derived CRC cell line CT26 and mesenchymal stem cells. The treatment experiments were followed by comprehensive gene expression analyses with RNA sequencing. Database analyses and immunohistochemistry research on clinical specimens revealed that LAT1 expression was cancer-dominant, and its increase was accompanied by tumor progression. In vitro, JPH203 was effective in an LAT1 expression-dependent manner. In vivo, JPH203 treatment considerably reduced tumor size and metastasis, and RNA sequencing-based pathway analysis showed that not only tumor growth and amino acid metabolism pathways, but also stromal activation-related pathways were suppressed. The results of the RNA sequencing were validated in the clinical specimens, as well as both in vitro and in vivo. LAT1 expression in CRC plays an important role in tumor progression. JPH203 may inhibit the progression of CRC and tumor stromal activity.
