Ischemic events after percutaneous coronary intervention (PCI) remain a major concern for patients with coronary heart disease (CHD). The aim of the current study was to investigate whether thromboelastography (TEG) was a satisfactory technique to measure platelet function in vitro in order to improve risk stratification and the individual response to antiplatelet therapy. The diagnostic and prognostic utility of the maximum amplitude of adenosine diphosphate induced platelet-fibrin clots (MAADP) was measured with TEG in 759 patients undergoing elective PCI. A 600-mg dose of clopidogrel was taken more than 12 h before surgery in addition to a maintenance dose of aspirin 100 mg/day and clopidogrel 75 mg/day for 2 y. Platelet-fibrin clot strength was also measured in this study. An MAADP > 34 mm significantly predicted ischemic events after PCI, as indicated by an area under the curve (AUC) of 0.79 (95% CI: 0.72-0.87, P < 0.05) according to receiver operating characteristic (ROC) curve analysis. The multivariate Cox proportional hazards model identified MAADP > 34 mm and an FBG level > 7.0 mmol/L as significant independent predictors of first ischemic events at the 2-year time point (P < 0.05). With adequate clopidogrel pretreatment, patients who underwent elective PCI and who experienced ischemic events could be diagnosed with a certain MAADP according to TEG. TEG could be a good tool to measure platelet function.
Recent studies facilitated by DNA sequencing identified the histone modifying gene SETD2 as the second most frequent mutant gene in sporadic clear cell renal cell carcinoma (ccRCC) patients. SETD2 functions as a tumor suppressor in ccRCC. However, its clinical association and biological functions are not fully delineated. The aim of this study is to evaluate the clinical significance of SETD2 in ccRCC patients. SETD2 and its canonical histone modification product H3K36me3 were analyzed by immunohistochemistry (IHC) in 155 ccRCC patients from two independent cohorts retrospectively. Both SETD2 and H3K36me3 were heterogeneously stained and down-regulated in ccRCC tissues, compared with normal controls. The SETD2 protein deficiency rate was 34.07%, which is much higher than the reported SETD2 gene inactive mutation rate. Furthermore, low SETD2 protein expression, but not H3K36me3 expression, was associated with the aggressive phenotype of ccRCC patients. In addition, cox multivariate analysis identified low SETD2 protein expression as an independent prognostic factor for overall survival of ccRCC patients. Consistently, using RNA-Seq data of ccRCC patients from The Cancer Genome Atlas, we validated our findings that low SETD2 mRNA expression is significantly associated with the aggressive phenotypes, and predicted a worse outcome for ccRCC patients. In conclusion, our study demonstrated a massive down-regulation of SETD2 protein in ccRCC, and identified SETD2 protein, but not H3K36me3, as an independent good prognostic marker, which warrants further study focusing on the non-methyltransferase role of SETD2 in kidney tumor biology.
Eleonora G. Dimitrova, Borislav G. Chaushev, Nikolay V. Conev, Javor K. Kashlov, Aleksandar K. Zlatarov, Dilyan P. Petrov, Hristo B. Popov, Nadezhda T. Stefanova, Anelia D. Klisarova, Kameliya Z. Bratoeva, Ivan S. Donev
The current study sought to evaluate the predictive and prognostic performance of the maximum standardized uptake value (SUVmax) prior to treatment in 43 patients with colon cancer and unresectable liver metastases. Patients with colon cancer who underwent 18F-FDG-PET/computed tomography (CT) scans for staging before the start of first-line 5-fluorouracil-based chemotherapy were retrospectively analyzed. Expression of Beclin-1 in cancer cells was evaluated in primary tumors using immunohistochemical staining. The pretreatment SUVmax for liver metastases was not able to predict progression-free survival but was significantly associated with poorer overall survival, with a hazard ratio of 2.05 (95 % CI, 1.016-4.155). Moreover, a negative correlation was noted between SUVmax and expression of a marker of autophagy – Beclin-1 (rho = -0.42, p = 0.006). This suggests that the pretreatment SUVmax in 18F-FDG PET/CT is a useful tool to help predict survival outcome in patients with colon cancer and unresectable liver metastases and may significantly distinguish between patients with low and high levels of Beclin-1 expression (AUC = 0.809, 95% CI: 0.670-0.948, p = 0.001).
Pseudomonas fluorescens is a plant growth promoting rhizobacterium that provides nutrients for growth and induces systemic resistance against plant diseases. It has been linked with a number of human diseases including nosocomial infections and bacterial cystitis. Chemotactic motility of P. fluorescens towards root exudates plays a crucial role in establishing a symbiotic relationship with host plants. The P. fluorescens chemotactic transducer of amino acids type B (CtaB) mediates chemotaxis towards amino acids. As a step towards elucidation of the structural basis of ligand recognition by CtaB, we have produced crystals of its recombinant sensory domain and performed their X-ray diffraction analysis. The periplasmic sensory domain of CtaB has been expressed, purified, and crystallized by the hanging-drop vapor diffusion method using ammonium sulfate as a precipitating agent. A complete data set was collected to 2.2 Å resolution using cryocooling conditions and synchrotron radiation. The crystals belong to space group P212121, with unit-cell parameters a = 34.5, b = 108.9, c = 134.6 Å. Calculation of the Matthews coefficient and the self-rotation function using this data set suggested that the asymmetric unit contains a protein dimer. Detailed structural analysis of CtaB would be an important step towards understanding the molecular mechanism underpinning the recognition of environmental signals and transmission of the signals to the inside of the cell.
Ovarian cancer is one of the common gynecological malignancies worldwide. It is usually diagnosed at a later stage, thus missing the best opportunity for treatment. Despite the advancement of ovarian cancer treatment, the prognosis is still poor. Androgen receptor (AR) may play a role in ovarian carcinogenesis. Previous studies regarding the association between AR CAG repeat length and ovarian cancer risk reported inconsistent results. Therefore, we conducted a meta-analysis to evaluate the association between AR CAG repeat length and ovarian cancer risk following the MOOSE guidelines. PubMed, Web of Science, EBSCO and other databases were searched up to September 15th 2016. Case control studies with clear definition of CAG repeat length and detailed genotype information were included. Two authors independently reviewed and extracted data. Pooled analysis and subgroup analysis stratified by ethnicity were performed for different genetic models. Begg's funnel plot and Egger's test were performed for publication bias estimation. Overall, there was no association between the AR CAG repeat polymorphism and ovarian cancer risk. However, short CAG repeat polymorphism was associated with increased ovarian cancer risk in African Americans and Chinese under the dominant model, whereas a reverse association was observed in Caucasians and Italians under the other three models. Our study results should be interpreted with caution. Further well-designed epidemiological and functional studies are needed to elucidate the role of AR in ovarian carcinogenesis.
Because of the prevalence of viral hepatitis and nonalcoholic fatty liver disease (NAFLD), liver fibrosis has become a very common disease in Asia and elsewhere in the world, constantly increasing the burden of care borne by society. Hepatic sinusoidal capillarization, characterized by gradually shrinking fenestrae on the surface of liver sinusoidal endothelial cells (LSECs) and the formation of an organized basement membrane, is an initial pathologic change associated with liver fibrosis. Basic and clinical studies have indicated that LSECs play a key role in hepatic sinusoidal capillarization by affecting various aspects of the development and progression of liver fibrosis. Reviewing studies on the effect of LSECs on liver fibrosis is essential to better understanding the pathogenesis of liver fibrosis and its mechanism of progression. Moreover, such a review will provide a theoretical basis for identifying new methods to promote the regression or even inhibition of fibrosis. This review will focus on structural and functional changes in LSECs during hepatic sinusoidal capillarization and the interaction between the micro-environment of the liver and the body's immune system.
A complex PGRMC1-centred regulatory system controls multiple cell functions. Although PGRMC1 is phosphorylated at several positions, we do not understand the mechanisms regulating its function. PGRMC1 is the archetypal member of the membrane associated progesterone receptor (MAPR) family. Phylogentic comparison of MAPR proteins suggests that the ancestral metazoan "PGRMC-like" MAPR gene resembled PGRMC1/PGRMC2, containing the equivalents of PGRMC1 Y139 and Y180 SH2 target motifs. It later acquired a CK2 site with phosphoacceptor at S181. Separate PGRMC1 and PGRMC2 genes with this "PGRMC-like" structure diverged after the separation of vertebrates from protochordates. Terrestrial tetrapods possess a novel proline-rich PGRMC1 SH3 target motif centred on P64 which in mammals is augmented by a phosphoacceptor at PGRMC1 S54, and in primates by an additional S57 CK2 site. All of these phosphoacceptors are phosphorylated in vivo. This study suggests that an increasingly sophisticated system of PGRMC1-modulated multicellular functional regulation has characterised animal evolution since Precambrian times.
Fibroblasts play several homeostatic roles, including electrical coupling, paracrine signaling and tissue repair after injury. Fibroblasts have low secretory activity. However, in response to injury, they differentiate to myofibroblasts. These cells have an increased extracellular matrix synthesis and secretion, including collagen fibers, providing stiffness to the tissue. In pathological conditions myofibroblasts became resistant to apoptosis, remaining in the tissue, causing excessive extracellular matrix secretion and deposition, which contributes to the progressive tissue remodeling. Therefore, increased myofibroblast content within damaged tissue is a characteristic hallmark of heart, lung, kidney and liver fibrosis. Recently, it was described that cardiac fibroblast to myofibroblast differentiation is triggered by the transforming growth factor β1 (TGF-β1) through a Smad-independent activation of Forkhead box O (FoxO). FoxO proteins are a transcription factor family that includes FoxO1, FoxO3, FoxO4 and FoxO6. In several cells types, they play an important role in cell cycle arrest, oxidative stress resistance, cell survival, energy metabolism, and cell death. Here, we review the role of FoxO family members on the regulation of cardiac fibroblast proliferation and differentiation.
The optimal surgical strategy for treating colorectal cancer with synchronous liver metastases is subject to debate. The current study sought to evaluate the outcomes of simultaneous colorectal cancer and liver metastases resection in a single center. Prospectively collected data on all patients with synchronous colorectal liver metastases who underwent simultaneous resection with curative intent were analyzed retrospectively. Patient outcomes were compared depending on the primary tumor location and type of liver resection (major or minor). Between January 2005 and August 2016, 108 patients underwent simultaneous resection of primary colorectal cancer and liver metastases. The tumor was localized to the right side of the colon in 24 patients (22%), to the left side in 40 (37%), and to the rectum in 44 (41%). Perioperative mortality occurred in 3 patients (3%). Postoperative complications were noted in 32 patients (30%), and most of these complications (75%) were grade 1 to 3 according to the Clavien-Dindo classification. Neither perioperative mortality nor the rate of postoperative complications after simultaneous resection differed among patients with cancer of the right side of the colon, those with cancer of the left side of the colon, and those with rectal cancer (4%, 2.5%, and 2%, respectively, p = 0.89) and (17%, 33%, and 34%, respectively; p = 0.29)]. The 5-year overall survival of the entire sample was 54% and the 3-year overall survival was 67 %. In conclusion, simultaneous resection for primary colorectal cancer and liver metastases is a safe procedure and can be performed without excess morbidity in carefully selected patients regardless of the location of the primary tumor and type of hepatectomy.
Edited and published by : International Research and Cooperation Association for Bio & Socio-Sciences Advancement Produced and listed by : International Advancement Center for Medicine & Health Research