Notes

Aftereffect of second-line chemo in treating relapsed or even refractory soften big W cellular lymphoma and prospects investigation.
AIMS Electro-acupuncture pretreatment (EAP) plays a protective role in myocardial ischemia (MI) injury. However, the underlying mechanism remains unclear. A growing body of evidence suggests postinfarction inflammatory response directly affects the remodeling of ventricular function. The purpose of this study was to investigate whether EAP alleviates MI through NLRP3 inflammasome inhibition. MATERIALS AND METHODS We constructed an AMI model by ligating the left anterior descending (LAD) coronary artery after 3 days of EAP with C57BL/6 mice. Echocardiography and TTC staining were employed to evaluate cardiac function and infarct size after 24 h of ischemia. HE staining and immunohistochemistry were employed to determine inflammatory level. Then, inflammasome activation was detected by western blotting, and macrophage polarization and neutrophil infiltration were observed by flow cytometry. KEY FINDINGS Our preliminary findings showed that EAP reduced the infarct area and increased fractional shortening (FS) and ejection fraction (EF) and decreased the degree of inflammation after AMI injury. Meanwhile, EAP inhibited the expression of NLRP3, cleaved caspase-1 and IL-1β in ischemia myocardial tissue, companied by inhibiting the expression of F4/80+, CD11b+, CD206low macrophages and activated M2 macrophage, and decreasing Ly-6G+CD11b+ neutrophils in ischemia myocardial and spleen tissue. SIGNIFICANCE EAP inhibits the activation of NLRP3 inflammasome, promotes M2 polarization of macrophages and reduces the recruitment of neutrophils in damaged myocardium, thereby decreases the infarct size and improves the cardiac function. AIMS Prostate cancer (PCa) is the most common type of cancer and a major cause of death in men worldwide. Aberrant Androgen receptor (AR) and PI3K-AKT signaling are very frequent in PCa patients and, therefore, considered as therapeutic targets in the clinic. Sin1 is an essential component of mTORC2 complex, which determines full AKT activation and PCa development in PTEN-/- mice. Here we examined the role of Sin1 in human PCa cell lines and respective tumor samples. MAIN METHODS Western blotting and immunohistochemistry (IHC) were performed to analyze the expression of Sin1-mTORC2-AKT related proteins in human PCa cells, as well as prostate tumors and normal tissue counterparts. Cell viability and invasion assays were also pursued in the presence or not of Sin1 in PCa cells. Immunoprecipitation assays were additionally carried out to examine the interaction of Sin1 with AR. KEY FINDINGS We have presently demonstrated that high levels of Sin1 expression in human PCa tissues correlate with cancer progression. Sin1-mediated cell proliferation and invasion of PCa cells occurs by regulating mTORC2-AKT signaling, epithelial-mesenchymal transition and matrix metalloproteinases. Moreover, androgens are able to induce Sin1 expression, which is further translocated to the nucleus of PCa cells. Finally, Sin1 interacts with AR to suppress its transcriptional activity. SIGNIFICANCE Taken together, these data indicate that both Sin1-mediated mTORC2-AKT signaling and Sin1-AR interaction regulate PCa development. Hence, Sin1 may be considered a novel biomarker of PCa progression. AIMS Dihydroartemisinin (DHA) is currently considered as the promising cancer therapeutic drug. In this study, we aimed to investigate the anti-proliferative and anti-metastasis effects of DHA. MAIN METHODS Utilizing breast cancer cells MCF-7, MDA-MB-231 and BT549, cell proliferation, migration and invasion were detected. RT-qPCR was performed to detect CIZ1, TGF-β1 and Snail expression, and the interactions of these related molecules were analyzed by GeneMANIA database. Western blot detected CIZ1, TGF-β1/Smads signaling and Snail expression in DHA-treated cells, in TGFβ1-induced cells with enhanced metastatic capacity, and in cells treated with DHA plus TGFβ1/TGFβ1 inhibitor SD-208. KEY FINDINGS Results indicated DHA inhibited breast cancer cell proliferation and migration, with more potent effects compared with that of artemisinin. RT-qPCR and Western blot showed DHA inhibited CIZ1, TGF-β1 and Snail expression, and these molecules were shown to have protein-protein interactions by bioinformatics. Furthermore, TGFβ1-treatment enhanced MCF-7 migration and invasion, and CIZ1, TGF-β1/Smads signaling and snail activities; DHA, SD-208, combination of DHA and SD-208 reversed these conditions, preliminarily proving the cascade regulation between TGF-β1 signaling and CIZ1. MCF-7 xenografts model demonstrated the inhibition of DHA on tumor burden, and its mechanisms and well-tolerance in vivo; combination of DHA and SD-208 tried by us for the first time showed better treatment effects, but possible liver impairment made its use still keep cautious. SIGNIFICANCE DHA treatment inhibits the proliferation and metastasis of breast cancer, through suppressing TGF-β1/Smad signaling and CIZ1, suggesting the promising potential of DHA as a well-tolerated antitumor TGF-β1 pathway inhibitor. BACKGROUND Intracerebral hemorrhage (ICH) can lead to inflammation. Serum amyloid A (SAA) is an acute phase protein, which might be implicated in acute brain injury. We ascertain relationship between serum SAA and inflammation, severity plus outcome after ICH. METHODS In this prospective, observational study, serum SAA concentrations were quantified in 159 healthy volunteers and 159 acute primary basal ganglia hemorrhage patients admitted within 24 h after stroke symptom. Prognostic parameters included death and a poor outcome (modified Rankin Scale score > 2) at 90 days after stroke. RESULTS Serum SAA concentrations were substantially higher in patients than in controls. Among patients, serum SAA concentrations were strongly correlated with serum C-reactive protein concentrations, hematoma volume and National Institutes of Health Stroke Scale scores. Serum SAA appeared to be an independent predictor for 90-day death, overall survival and poor outcome. Under receiver operating characteristic curve, this protein exhibited similar prognostic capability, as compared to hematoma volume and National Institutes of Health Stroke Scale scores. CONCLUSIONS Rising serum SAA concentrations, in close correlation with inflammation and hemorrhagic severity, are independently related to mortality and poor outcome after ICH, indicating that serum SAA might serve as a potential prognostic biomarker for ICH. Chromothripsis is a unique type of genomic instability and is recognized in various cancers. In myeloid neoplasms (MNs), chromothripsis was linked to poor prognosis and specific genetic alterations (complex karyotype, 5q deletions, and loss of TP53). However, the clinicopathologic features of MNs with chromothripsis have not been thoroughly characterized. We identified chromothripsis in 11 cases of MNs (9 acute myeloid leukemia [AML] and 2 myelodysplastic syndrome [MDS] cases) and noted that all chromothripsis-positive AML cases were AML with myelodysplasia-related changes (AML-MRC). We performed a comparative clinicopathologic and genetic characterization of AML-MRC cases with and without chromothripsis. AML-MRC with chromothripsis is associated with lower white blood cell and platelet counts and higher degree of karyotypic complexity. Chromothripsis in AML-MRC most frequently involves chromosomes 8 and 11 with consequent amplification of either MYC or KMT2A. Comparative morphologic assessment of blast morphology revealed unique features characteristic of AML-MRC with chromothripsis a variable degree of cytoplasmic vacuolization, granulation, and blebbing. These morphologic markers in the context of AML-MRC may prompt additional studies to identify cases with chromothripsis. Juvenile papillomatosis (JP), the so-called Swiss cheese disease is a rare benign breast disease of young adults. An association (up to 28 %) with breast-cancer within the family of affected patients has been reported. A multinodular cystic breast-mass lesion and calcifications characterizes JP in imaging studies. The histological picture is diverse and comprises multiple intraductal-papillomas, usual ductal hyperplasia (UDH), ductectasias, perifocal sclerosing adenosis and calcification. Patients with complete excision of JP lesions have an excellent follow-up; breast cancer develops only on a very low subset of patients. Molecular background of JP has not been investigated until now. In this study, we addressed mutational analysis of JP cases and correlated these results with follow-up and family-history in context with a comprehensive review of JP literature. We identified 13 cases fulfilling the criteria of JP. All patients were female with a median-age of 38 years (26 to 50 years). Follow-up information gh these mutations are not specific for JP. The genetic link between JP, positive family history and subsequent risk of breast cancer, needs further studies. BACKGROUND Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has demonstrated high efficacy with a favorable safety profile in various psoriatic disease manifestations. TRIAL DESIGN AND METHODS Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, moderate-to-severe psoriasis patients received secukinumab for 40 weeks. Vascular inflammation using FDG-PET/CT imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. RESULTS The difference in change in aortic inflammation from baseline to Week 12 for secukinumab (N=46) versus placebo (N=45) was -0.053 (95% CI -0.169, 0.064; P=0.37). Small increases in total cholesterol, LDL, and LDL particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At Week 52, reductions in TNF-α (P=0.0063) and ferritin (P=0.0354), and an increase in fetuin A (P=0.0024), were observed with secukinumab treatment compared to baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared to baseline. CONCLUSION Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment. BACKGROUND AND AIMS The heterogeneity among colorectal tumors is probably due to differences in developmental pathways and might associate with patient survival times. We studied the relationship among markers of different subtypes of colorectal tumors and patient survival. METHODS We pooled data from 7 observational studies, comprising 5010 patients with colorectal cancer. All the studies collected information on microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in KRAS and BRAF in tumors. Tumors with complete marker data were classified as type 1 (MSI high, CIMP positive, with pathogenic mutations in BRAF but not KRAS), type 2 (not MSI high, CIMP positive, with pathogenic mutations in BRAF but not KRAS); type 3 (not MSI high or CIMP, with pathogenic mutations in KRAS but not BRAF); type 4 (not MSI-high or CIMP, no pathogenic mutations in BRAF or KRAS), or type 5 (MSI-high, no CIMP, no pathogenic mutations in BRAF or KRAS). We used Cox regression to estimate hazard ratios (HR) and 95% CIs for associations of these subtypes and tumor markers with disease-specific survival (DSS) and overall survival (OS) times, adjusting for age, sex, stage at diagnosis, and study population.
My Website: