From oxygen sensing to heart failure: role of thioredoxin

Oxidative stress has been widely recognized to be involved in the pathogenesis of cardiopulmonary disorders. In ischemic heart diseases, it is involved not only in the development of atherosclerosis but also in ongoing ischemic injury, especially in the reperfusion process. Cardiomyopathy is another cardiac disorder in which oxidative stress is involved. In diabetic cardiomyopathy, homocysteine, a well-known source of oxidative stress, is believed to play major roles in its development. Thioredoxin (TRX) is a redox-acting protein ubiquitously present in the human body. It also is inducible by a wide variety of oxidative stresses. TRX is a multifunctional protein and has anti-inflammatory and antiapoptotic effects, as well as antioxidative effects. It is therefore feasible to think that TRX is a potential therapy for cardiac disease. Moreover, serum TRX is a well-recognized biomarker of various diseases involving oxidative stress, and this is also the case for cardiac disorders. Here we discuss how TRX is useful as a biomarker of and therapeutic agent for cardiopulmonary disorders, especially focusing on ischemic heart disease, myocarditis and oxygen sensing, and acute respiratory distress syndrome.     

Association of thoracic kyphosis with subjective poor health, functional activity and blood pressure in the community-dwelling elderly

Objectives The prevalence of thoracic kyphosis is considered to increase as the population is ageing in Japan. However, little is known about the clinical and preventive significance of kyphosis. The purpose of the study is to assess the association of kyphosis with subjective poor health and functional activity in the community-dwelling Japanese elderly. The relation of kyphosis with blood pressure, as a subclinical indicator of arteriosclerosis, is also examined. Methods The subjects consisted of 536 (male 241, female 295) elderly persons aged 65 years old and older. Trained examiners measured thoracic kyphosis using a flexicurve, and kyphosis index was calculated. Information on the subjects’ subjective poor health and functional activity were collected through a face-to-face interview, and blood pressure was measured by a conventional method. Results In females, their kyphosis index increased with age increased, whereas in males, there was no clear age-related change. An increased kyphosis index was associated with subjective poor health only among females. Compared with the lowest kyphosis index tertile, adjusted odds ratios for being in poor health were 5.4 (95% confidence interval: 1.1–27.4) in the middle tertile, and 6.4 (95% confidence interval: 1.3–32.1) in the highest tertile. Kyphosis index did not seem to be associated with functional activity score and blood pressure both in males and females even after adjustment. Conclusions Kyphosis is associated with subjective poor health in the community-dwelling female elderly in this study population, but not with functional activity and blood pressure both in males and females.     

Gene expression profiling of 19q-loss astrocytomas suggest a specific pattern associated with the better prognosis

Journal of Neuro-Oncology - Awake surgery is the standard treatment to preserve motor and language functions. This longitudinal study aimed to evaluate the resection rate and preservation of...     

Negative prognostic outcomes of percutaneous transhepatic biliary drainage in distal cholangiocarcinoma: a retrospective analysis using propensity score matching

International Journal of Clinical Oncology - The efficacy of different types of preoperative biliary drainage for cholangiocarcinoma has been debated over the past two decades. Controversy...     

Multiple mutations within individual oncogenes

Recent studies of the cancer genome have identified numerous patients harboring multiple mutations (MM) within individual oncogenes. These MM (de novo MM) in cis synergistically activate the mutated oncogene and promote tumorigenesis, indicating a positive epistatic interaction between mutations. The relatively frequent de novo MM suggest that intramolecular positive epistasis is widespread in oncogenes. Studies also suggest that negative and higher‐order epistasis affects de novo MM. Comparison of de novo MM and MM associated with drug‐resistant secondary mutations (secondary MM) revealed several similarities with respect to allelic configuration, mutational selection and functionality of individual mutations. Conversely, they have several differences, most notably the difference in drug sensitivities. Secondary MM usually confer resistance to molecularly targeted therapies, whereas several de novo MM are associated with increased sensitivity, implying that both can be useful as therapeutic biomarkers. Unlike secondary MM in which specific secondary resistant mutations are selected, minor (infrequent) functionally weak mutations are convergently selected in de novo MM, which may provide an explanation as to why such mutations accumulate in cancer. The third type of MM is MM from different subclones. This type of MM is associated with parallel evolution, which may contribute to relapse and treatment failure. Collectively, MM within individual oncogenes are diverse, but all types of MM are associated with cancer evolution and therapeutic response. Further evaluation of oncogenic MM is warranted to gain a deeper understanding of cancer genetics and evolution.     

The clinicopathological characteristics of muscle-invasive bladder recurrence in upper tract urothelial carcinoma

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2-4N0-2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non-MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.     

Effects of transurethral resection under general anesthesia on tumor recurrence in non-muscle invasive bladder cancer

International Journal of Clinical Oncology - The effects of the type of anesthesia (spinal (SA) vs. general (GA)) used for transurethral resection of bladder tumor (TURBT) on non-muscle invasive...     

The protective effect of interleukin-11 on the cell death induced by X-ray irradiation in cultured intestinal epithelial cell

Interleukin-11 (IL-11) is a well known anti-inflammatory cytokine that is associated with cell growth, and also participates in limiting X-ray irradiation induced intestinal mucosal injury. The aim of this study was to evaluate the protective effect of IL-11 on the cell injury induced by X-ray irradiation in rat intestinal epithelial IEC-18 cells. Recombinant human IL-11 (rhIL-11) treated cells were irradiated and then examined for cell viability. To evaluate irradiation injury, trypan blue staining was used to detect the dead cells. The viability of irradiated cells was up-regulated by rhIL-11 treatment and also resulted in the activation of p90 ribosomal S6 kinase (p90RSK) and S6 ribosomal protein (S6Rp). Wortmannin, a specific inhibitor of PI3K, suppressed the activation of S6Rp in rhIL-11 treated cells, and decreased the up-regulation of viability by rhIL-11 treatment in irradiated cells. The TUNEL assay was also perfomed to estimate the rate of apoptosis in X-ray induced cell death. There was no difference in the results between trypan blue staining and the TUNEL assay. Further, rhIL-11 down-regulated the expression of cleaved caspase-3 in irradiated cells. These results suggest that rhIL-11 may play an important role in protection from radiation injury.     

Extracts of Momordica charantia suppress postprandial hyperglycemia in rats

Momordica charantia (bitter melon) is commonly known as vegetable insulin, but the mechanisms underlying its hypoglycemic effect remain unclear. To address this issue, the effects of bitter melon extracts on postprandial glycemic responses have been investigated in rats. An aqueous extract (AE), methanol fraction (MF) and methanol insoluble fraction (MIF) were prepared from bitter melon. An oral sucrose tolerance test revealed that administration of AE, MF or MIF each significantly suppressed plasma glucose levels at 30 min as compared with the control. In addition, the plasma insulin level at 30 min was also significantly lower after MF administration than in the control in the oral sucrose tolerance test. By contrast, these effects of bitter melon extracts were not observed in the oral glucose tolerance test. In terms of mechanism, bitter melon extracts dose-dependently inhibited the sucrase activity of intestinal mucosa with IC(50) values of 8.3, 3.7 and 12.0 mg/mL for AE, MF and MIF, respectively. The fraction with a molecular weight of less than 1,300 (LT 1,300) obtained from MF inhibited the sucrase activity most strongly in an uncompetitive manner with an IC(50) value of 2.6 mg/mL. Taken together, these results demonstrated that bitter melon suppressed postprandial hyperglycemia by inhibition of alpha-glucosidase activity and that the most beneficial component is present in the LT 1,300 fraction obtained from MF.     

Isolation of <Emphasis Type="Italic">Pteropine orthoreovirus</Emphasis> from <Emphasis Type="Italic">Pteropus vampyrus</Emphasis> in Garut,Indonesia

Flying foxes belonging to the genus Pteropus are known to be reservoirs of zoonotic viruses. In this study, we describe the isolation of Pteropine orthoreovirus (PRV) from rectal swab samples of Pteropus vampyrus in Indonesia. PRV is an emerging zoonotic respiratory virus that can be transmitted from bats to humans. Rectal swabs (n?=?91) were screened by PCR for PRV and 10 (11%) were positive. Phylogenetic analysis based on nucleotide sequences indicated that the S2, S3, S4, M3, L2, and L3 segments of one isolate (Garut-69) were closely related to previously isolated strains in Indonesia. The remaining gene segments showed both similarity and genetic divergence with other PRV strains, suggesting that re-assortment events had occurred. This is the first report of PRV infection to P. vampyrus in West Java, Indonesia.