Pilot Study on Clinical Effectiveness of Autofluorescence Imaging for Early Gastric Cancer Diagnosis by Less Experienced Endoscopists

This study aimed to assess and compare effectiveness of Autofluorescence imaging (AFI) in diagnosis of early gastric cancer (EGC) between experienced and less experienced endoscopists. Fifty selected images (20 neoplastic lesions and 30 benign lesions/areas) of both white light endoscopy (WLE) and AFI were blindly reviewed by two groups; first consisted of five experienced endoscopists and second included five less experienced endoscopists. Sensitivity, specificity, and accuracy were 70%, 78%, and 75%, respectively, for AFI and 81%, 76%, and 78%, respectively, for WLE in the experienced group. In the less experienced group, sensitivity, specificity and accuracy were 80%, 81% and 80%, respectively, for AFI and 65%, 77%, and 72%, respectively, for WLE. Interobserver variability for the less experienced group was better with AFI than WLE. AFI improved sensitivity of endoscopic diagnosis of neoplastic lesions by less experienced endoscopists, and its use could beneficially enhance the clinical effectiveness of EGC screening

Decreased responsiveness of naturally occurring mutants of human estrogen receptor α to estrogens and antiestrogens

金沢大学大学院医学系研究科機能分子医薬学Estrogen receptor α (ERα) is a ligand-inducible transcription factor that mediates the biological effects of estrogens and antiestrogens. Many point mutations in the human ERα gene have been reported to be associated with breast cancer, endometrial cancer, and psychiatric diseases. However, functional analyses for most mutants with amino acid changes are still lacking. In the present study, to investigate the effects of point mutations on the function, gel-shift assays and luciferase assays were performed for eight kinds of mutated ERα proteins, including a single nucleotide change of C207G (N69K), G478T (G160C), T887C (L296P), A908G (K303R), C926T (S309F), A1058T (E353V), A1186G (M396V), and G1231deletion (411fsX7). The mutated ERα expression plasmids were constructed by site-directed mutagenesis. With gel-shift assays using in vitro translated ERα proteins, binding to the consensus estrogen response element (ERE) was observed for the mutated ERα proteins except ERα (G160C) and ERα (411fsX7), the binding of which was comparable with that of the wild type. Western blot analyses showed that ERα (G160C) could not be efficiently translated with the in vitro transcription/translation system and that ERα (411fsX7) produced a truncated protein. To investigate the transactivation potency, wild-type or mutated ERα expression plasmids were co-transfected with pGL3-3EREc38 reporter plasmid into human breast adenocarcinoma MDA-MB-435 cells. The concentration-response curves (10 pM-100 nM E2) of the mutant ERα proteins except ERα (E353V) and ERα (411fsX7) were similar to that of wild-type ERα. However, at a low level of E2 (100 pM), the mutants ERα (N69K), ERα (L296P), ERα (S309F), and ERα (M396V) showed a significant decrease of transactivation compared with that of the wild-type ERα. The mutants ERα (E353V) and ERα (411fsX7) did not show responsiveness to E2 and antiestrogens, 4-hydroxytamoxifen (4OHT) and ICI 182,780. The mutant ERα (S309F) showed decreased responsiveness for the antiestrogenicity of 4OHT. In conclusion, we found that some of the naturally occurring human ERα mutants with amino acid changes may have an altered responsiveness to estrogen and antiestrogens. © 2006 Elsevier Ltd. All rights reserved

Combination Treatment of Perioperative Rehabilitation and Psychoeducation Undergoing Thoracic Surgery

Postoperative pulmonary complications are a risk associated with thoracic surgery. However, there have been few reports on cases at high risk of postoperative complications. Cancer patients often have negative automatic thoughts about illness, and these negative automatic thoughts are associated with reduced health behavior and physical activity. This case series demonstrates the successful combination treatment of perioperative rehabilitation and psychoeducation for negative automatic thoughts in two cancer patients who underwent thoracic surgery. One patient underwent pneumonectomy with laryngeal recurrent nerve paralysis; the other patient, who had a history of recurrent hepatic encephalopathy and dialysis, underwent S6 segmentectomy. Both patients had negative automatic thoughts about cancer-related stress and postoperative pain. The physical therapists conducted a perioperative rehabilitation program in which the patients were educated to replace their maladaptive thoughts with more adaptive thoughts. After rehabilitation, the patients had improved adaptive thoughts, increased physical activity, and favorable recovery without pulmonary complications. This indicates that the combination treatment of perioperative rehabilitation and psychoeducation was useful in two thoracic cancer surgery patients. The psychoeducational approach should be expanded to perioperative rehabilitation of patients with cancer

Deregulated GSK3β sustains gastrointestinal cancer cells survival by modulating human telomerase reverse transcriptase and telomerase

金沢大学がん研究所分子標的がん医療研究開発センターPurpose: Glycogen synthase kinase-3β (GSK3β) regulates multiple cell signaling pathways and has been implicated in glucose intolerance, neurodegenerative disorders, and inflammation. We investigated the expression, activity, and putative pathologic role of GSK3β in gastrointestinal, pancreatic, and liver cancers. Experimental Design: Colon, stomach, pancreatic, and liver cancer cell lines; nonneoplastic HEK293 cells; and matched pairs of normal and tumor tissues of stomach and colon cancer patients were examined for GSK3β expression and its phosphorylation at serine 9 (inactive form) and tyrosine 216 (active form) by Western immunoblotting and for GSK3β activity by in vitro kinase assay. The effects of small-molecule GSK3β inhibitors and of RNA interference on cell survival, proliferation, and apoptosis were examined in vitro and on human colon cancer cell xenografts in athymic mice. The effects of GSK3β inhibition on human telomerase reverse transcriptase (hTERT) expression and telomerase activity were compared between colon cancer and HEK293 cells. Results: Cancer cell lines and most cancer tissues showed increased GSK3β expression and increased tyrosine 216 phosphorylation and activity but decreased serine 9 phosphorylation compared with HEK293 cells and nonneoplastic tissues. Inhibition of GSK3β resulted in attenuated cell survival and proliferation and increased apoptosis in most cancer cell lines and in HT-29 xenografts in rodents but not in HEK293 cells. GSK3β inhibition in colon cancer cells was associated with decreased hTERT expression and telomerase activity. Conclusion: The results indicate that deregulated GSK3β sustains gastrointestinal cancer cells survival through modulation of hTERT and telomerase. © 2009 American Association for Cancer Research

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in 2018

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in 2018

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI

Measurement of interleukins in vitreous infusion fluid

Measurements of interleukin (IL)-6 and -10 concentrations in the vitreous can be used to differentiate intraocular lymphoma (IOL) from uveitis. This is the first study reporting the IL-6 and -10 concentrations in the undiluted vitreous fluid and vitreous infusion fluid, which were simultaneously examined in the patients. A total of 2 females presented with intraocular inflammation, and underwent pars plana vitrectomy. Undiluted anterior vitreous and vitreous infusion fluid were collected simultaneously. IL concentrations were determined by enzyme-linked immunosorbent assay systems. Vitreous infusion fluid of 20 ml was eventually collected following completion of core vitrectomy in the two patients. IL-6 concentrations of the first patient were 513 and 106 pg/ml in the undiluted vitreous and the infusion fluid, respectively, while those of the second patient were 263 and 29 pg/ml. By contrast, IL-10 was under the detectable levels in all the fluids. The IL-10/-6 ratio was <1 in both fluids in the patients. Cytological examination revealed the presence of reactive inflammatory cells in the vitreous fluid. The two patients were eventually diagnosed with uveitis. Measurements of IL concentrations in the vitreous infusion fluid provided significant evidence on the differential diagnosis between IOL and uveitis, when considering how vitreous infusion fluid was diluted. The present study highlighted a novel application of cytokine analyses using the vitreous infusion fluid, which may contribute to the development of future translational researches on uveitis/IOL patients