Transthyretin cardiac amyloidosis (ATTR‐CA) demonstrates progressive, potentially fatal, and infiltrative cardiomyopathy caused by extracellular deposition of transthyretin‐derived insoluble amyloid ...fibrils in the myocardium. Two distinct types of transthyretin (wild type or variant) become unstable, and misfolding forms aggregate, resulting in amyloid fibrils. ATTR‐CA, which has previously been underrecognized and considered to be rare, has been increasingly recognized as a cause of heart failure with preserved ejection fraction among elderly persons. With the advanced technology, the diagnostic tools have been improving for cardiac amyloidosis. Recently, the efficacy of several disease‐modifying agents focusing on the amyloidogenic process has been demonstrated. ATTR‐CA has been changing from incurable to treatable. Nevertheless, there are still no prognostic improvements due to diagnostic delay or misdiagnosis because of phenotypic heterogeneity and co‐morbidities. Thus, it is crucial for clinicians to be aware of this clinical entity for early diagnosis and proper treatment. In this mini‐review, we focus on recent advances in diagnosis and treatment of ATTR‐CA.
DNA mismatch repair (MMR) deficiency results in a strong mutator phenotype and high-frequency microsatellite instability (MSI-H), which are the hallmarks of tumors arising within Lynch syndrome. ...MSI-H is characterized by length alterations within simple repeated sequences, microsatellites. Lynch syndrome is primarily due to germline mutations in one of the DNA MMR genes; mainly hMLH1 or hMSH2 and less frequently hMSH6 and rarely hPMS2. Germline hemiallelic methylation of MLH1, termed epimutation, has been reported to be a new cause of Lynch syndrome. MSI-H is also observed in ∼15% of colorectal, gastric and endometrial cancers and in lower frequencies in a minority of other tumors, where it is associated with the hypermethylation of the promoter region of hMLH1. MSI-H underlies a distinctive tumorigenic pathway because cancers with MSI-H exhibit many differences in genotype and phenotype relative to cancers without MSI-H, irrespective of their hereditary or sporadic origins. Genetic, epigenetic and transcriptomic differences exist between cancers with and those without the MSI-H. The BRAF V600E mutation is associated with sporadic MSI-H colorectal cancers (CRCs) harboring hMLH1 methylation but not Lynch syndrome-related CRCs. The differences in genotype and phenotype between cancers with and those without MSI-H are likely to be causally linked to their differences in biological and clinical features. Therefore, the diagnosis of MSI-H in cancers is thus considered to be of increasing relevance, because MSI-H is a useful screening marker for identifying patients with Lynch syndrome, a better prognostic factor and could affect the efficacy of chemotherapy. This review addresses recent advances in the field of microsatellite instability research.
IgG4-related disease (IgG4-RD) is considered a systemic, chronic, and inflammatory disorder that is characterized by the enlargement of involved organs, elevated levels of IgG4, and abundant ...infiltration of plasmacytes with IgG4 and fibrosis in involved organs. It is necessary to differentiate IgG4-RD from malignant tumors. Recently we have looked at case reports of IgG4-RD with malignancy that was discovered at systemic screening. In this study, we analyzed the relationship between IgG4-RD and malignancies. The study subjects were 106 patients with IgG4-RD who had been referred to our hospital since April 1997. We analyzed the clinical characteristics of IgG4-RD patients who had cancer that was observed upon the initial diagnosis of IgG4-RD or that occurred during an average follow-up period of 3.1 years. Using data from national cancer registries that monitor cancer incidence in Japan, we evaluated the standardized incidence ratio (SIR) for malignancies in IgG4-RD. Malignancies were observed in 11 of the IgG4-RD patients (10.4%). The malignancies were all different and included lung cancer, colon cancer, and lymphoma. With the exception of the age at which the IgG4-RD diagnosis was made, there were no common features in patients with cancer and those without. The SIR for these malignancies in IgG4-RD was 383.0, which was higher than that for the general population. We should be cognizant of the possible existence of malignancies in patients with IgG4-RD at the time of diagnosis and during follow-up care.
Non-destructive depth profiling with better depth resolution is required for the characterization of nano-materials. Sputter etching is commonly used as the conventional way of depth profiling. ...However, it causes damage because of atomic mixing and surface roughening by ion bombardment. X-ray photoelectron spectroscopy (XPS) is typically non-destructive analysis, however, XPS with a fixed excitation energy source cannot provide a depth profile without an additional technique. On the other hand, analyzing depth of XPS can be varied with energy tunable excitation source, such as synchrotron-radiation (SR), since the escape depth of photoelectrons depends on their kinetic energy. We can obtain XPS spectra from different analyzing depths by varying the excitation energy. This technique can provide depth profiles of the elements and their chemical states non-destructively. In the present study, thermally oxidized and O2+ ion implanted Si(100) surface, initial oxidation process of Fe-Cr (18 %) alloy surface, Ge (2∼4 nm) thin films on Si(100) have been analyzed. The measurements have been performed at KEK-PF, Tsukuba using 1.8∼6.0 keV X-ray. XPS spectra clearly show depth dependences, which can be interpreted into depth profile. Chemical state changes at the surface/interface are also clearly observed.
Background:Ventricular septal defect (VSD) after myocardial infarction (MI) is a rare but fatal complication. We report patients’ characteristics and operative outcomes after surgical repair of ...post-MI VSD using a national database of Japan.Methods and Results:This was a retrospective review of the Japan Adult Cardiovascular Surgery Database (JCVSD) to identify adults (age ≥18 years) who underwent surgical repair of post-MI VSD between 2008 and 2014. The primary outcome was operative death. We identified 1,397 patients (671 male 48%, 74.1±9.3 years old) undergoing surgical repair of post-MI VSD among 288,736 patients undergoing cardiac surgery enrolled in the JCVSD during the same period. Of these, 1,075 (77.0%) were supported preoperatively with an intra-aortic balloon pump. Surgical status was urgent in 391 (28.0%) and emergency/salvage in 731 (52.3%). Concomitant coronary artery bypass grafting was performed in 475 (34.0%). Overall 30-day and operative mortalities were 24.3% and 33.0%, respectively. Operative mortality varied according to surgical status: 15.6% in elective, 30.9% in urgent, and 40.6% in emergency/salvage cases. Multivariable analysis identified advanced age and emergency/salvage status as being strongly associated with increased odds of operative death.Conclusions:Post-MI VSD remains a devastating complication in Japan as well as in the USA and Europe.
OBJECTIVE:We aimed to elucidate whether minimally invasive esophagectomy (MIE) can be safely performed by reviewing the Japanese National Clinical Database.
SUMMARY OF BACKGROUND DATA:MIE is being ...increasingly adopted, even for advanced esophageal cancer that requires various preoperative treatments. However, the superiority of MIEʼs short-term outcomes compared with those of open esophagectomy (OE) has not been definitively established in general clinical practice.
METHODS:This study included 24,233 esophagectomies for esophageal cancer conducted between 2012 and 2016. Esophagectomy for clinical T4 and M1 stages, urgent esophagectomy, 2-stage esophagectomy, and R2 resection were excluded. The effects of preoperative treatment and surgery on short-term outcomes were analyzed using generalized estimating equations logistic regression analysis.
RESULTS:MIE was superior or equivalent to OE in terms of the incidence of most postoperative morbidities and surgery-related mortality, regardless of the type of preoperative treatment. Notably, MIE performed with no preoperative treatment was associated with significantly less incidence of any pulmonary morbidities, prolonged ventilation ≥48 hours, unplanned intubation, surgical site infection, and sepsis. However, reoperation within 30 days in patients with no preoperative treatment was frequently observed after MIE. The total surgery-related mortality rates of MIE and OE were 1.7% and 2.4%, respectively (P < 0.001). Increasing age, low preoperative activities of daily living, American Society of Anesthesiologists physical status ≥3, diabetes mellitus requiring insulin use, chronic obstructive pulmonary disease, congestive heart failure, creatinine ≥1.2 mg/dL, and lower hospital case volume were identified as independent risk factors for surgery-related mortality.
CONCLUSIONS:The results suggest that MIE can replace OE in various situations from the perspective of short-term outcome.
Deep-sea environments are faced with cumulative effects of many human activities, e.g. accumulation of plastics, overwhelming fishing and resource exploitation, heavy maritime transportation, and ...effects from climate change. Recently, growing interest in deep-sea mining enhances the activities of engineering development on seabed mining and environmental monitoring, and exploration of mining sites within States Exclusive Economic Zones (EEZ) or in areas beyond the limits of national jurisdiction. Since 2010, attention paid to potential environmental impacts caused by deep-sea mining has been increased, and many workshops and research conferences have been held. In the Western Pacific Ocean, the Nautilus Minerals Ltd. has announced that the sea mound located in Papua New Guinea will be a first site likely to be commercially exploited polymetallic sulfide deposit. The Japan Oil, Gas and Metals National Corporation (JOGMEC) conducts a feasibility project for seabed mining in the Okinawa Trough. In 2015, the leaders’ declaration from the G7 summit in Germany identified the conducting of Environmental Impact Assessment (EIA) and scientific research as a priority issue for sustainable development of deep-sea mining. The EIA protocol developed for deep-sea mining is recognized that it will be a practical component for ensuring effective management and protection of ocean ecosystems. The development of EIA protocols is started in Japan as a national project. This paper describes the current situation of technologies concerning deep-sea environmental assessment and monitoring on seabed mining, and technical background of multidisciplinary approaches for deep-sea environmental survey.
Comprehensive metabolomic analyses have been conducted in various institutes and a large amount of metabolomic data are now publicly available. To help fully exploit such data and facilitate their ...interpretation, metabolomic data obtained from different facilities and different samples should be integrated and compared. However, large-scale integration of such data for biological discovery is challenging given that they are obtained from various types of sample at different facilities and by different measurement techniques, and the target metabolites and sensitivities to detect them also differ from study to study. We developed iDMET, a network-based approach to integrate metabolomic data from different studies based on the differential metabolomic profiles between two groups, instead of the metabolite profiles themselves. As an application, we collected cancer metabolomic data from 27 previously published studies and integrated them using iDMET. A pair of metabolomic changes observed in the same disease from two studies were successfully connected in the network, and a new association between two drugs that may have similar effects on the metabolic reactions was discovered. We believe that iDMET is an efficient tool for integrating heterogeneous metabolomic data and discovering novel relationships between biological phenomena.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Large intergenic noncoding RNAs (lincRNA) have been less studied than miRNAs in cancer, although both offer considerable theranostic potential. In this study, we identified frequent upregulation of ...miR-196a and lincRNA HOTAIR in high-risk gastrointestinal stromal tumors (GIST). Overexpression of miR-196a was associated with high-risk grade, metastasis and poor survival among GIST specimens. miR-196a genes are located within the HOX gene clusters and microarray expression analysis revealed that the HOXC and HOTAIR gene were also coordinately upregulated in GISTs which overexpress miR-196a. In like manner, overexpression of HOTAIR was also strongly associated with high-risk grade and metastasis among GIST specimens. RNA interference-mediated knockdown of HOTAIR altered the expression of reported HOTAIR target genes and suppressed GIST cell invasiveness. These findings reveal concurrent overexpression of HOX genes with noncoding RNAs in human cancer in this setting, revealing miR-196a and HOTAIR as potentially useful biomarkers and therapeutic targets in malignant GISTs.
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