Polymorphisms and phenotypic analysis of cytochrome P450 3A4 in the Uygur population in northwest China.

Purpose: Genetic polymorphisms in CYP3A4 can change its activity to a certain degree, thus leading to differences among different populations in drug efficacy or adverse drug reactions.

Methods: The study was intended to validate the genetic polymorphisms in CYP3A4 in Uygur Chinese population, we sequenced and screened for genetic variants including 5'UTR, promoters, exons, introns, and 3'UTR region of the whole CYP3A4 gene in 100 unrelated, healthy.

Results: Twenty-one genetic polymorphisms in CYP3A4, and nine of them were novel.

Neutrophil count improves the GRACE risk score prediction of clinical outcomes in patients with ST-elevation myocardial infarction.

Objective: Both the Global Registry of Acute Coronary Events (GRACE) risk score and neutrophil count could predict clinical outcomes in patients with acute coronary syndromes. However, the ability of them to identify high risk patients leaves room for improvement. The purpose of the present study was to evaluate whether the combination of them could have a better performance in predicting clinical outcomes in patients with ST-elevation myocardial infarction (STEMI).

Association of colorectal cancer susceptibility variants with esophageal cancer in a Chinese population.

Aim: To investigate the association between colorectal cancer (CRC) genetic susceptibility variants and esophageal cancer in a Chinese Han population.

Methods: A case-control study was conducted including 360 esophageal cancer patients and 310 healthy controls. Thirty-one single-nucleotide polymorphisms (SNPs) associated with CRC risk from previous genome-wide association studies were analyzed.

High copy number of mitochondrial DNA (mtDNA) predicts good prognosis in glioma patients.

Alterations in mitochondrial DNA (mtDNA) copy number have been widely identified in many types of human cancers and are considered a common cancer hallmark. However, the prognostic value of altered mtDNA content in gliomas remains largely unknown. The aim of this study was to investigate mtDNA copy number in a cohort of gliomas (n = 124) and non-neoplastic brain tissues (control subjects; n = 27) and to explore the association between variable mtDNA content and clinical outcomes in glioma patients.

Frequent amplification of AIB1, a critical oncogene modulating major signaling pathways, is associated with poor survival in gastric cancer.

Amplified in breast cancer 1 (AIB1) is a member of p160 steroid receptor coactivator (SRC) family that mediates the transcriptional activities of nuclear receptors and other transcription factors. It acts as a major oncogene in diverse cancers, whereas biological function of AIB1 in gastric cancer remains largely unclear. This study was designed to explore the role of AIB1 in gastric tumorigenesis and its potential as a useful prognostic marker and therapeutic target in this cancer.

Genetic polymorphism analysis of the drug-metabolizing enzyme CYP2C9 in a Chinese Tibetan population.

Objectives: The enzymatic activity of CYP2C9 results in broad inter-individual variability in response to certain pharmacotherapies. The present study aimed to screen Tibetan volunteers for CYP2C9 genetic polymorphisms. Previous research has focused on Han Chinese patients, while little is known about the genetic variation of CYP2C9 in Tibetan populations.

Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth.

GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated (TamCart)Igf1r(flox/flox) mice.

Patient age, tumor appearance and tumor size are risk factors for early recurrence of cervical cancer.

The recurrence and metastasis of cervical cancer contribute to a poor prognosis. The aim of this study was to investigate the risk factors for cervical cancer progression. A total of 284 patients with recurrent cervical cancer were retrospectively recruited to evaluate the association of disease recurrence with clinicopathological data.

Frequent amplification of PTP1B is associated with poor survival of gastric cancer patients.

The protein tyrosine phosphatase 1B (PTP1B), a non-transmembrane protein tyrosine phosphatase, has been implicated in gastric pathogenesis. Several lines of recent evidences have shown that PTP1B is highly amplified in breast and prostate cancers. The aim of this study was to investigate PTP1B amplification in gastric cancer and its association with poor prognosis of gastric cancer patients, and further determine the role of PTP1B in gastric tumorigenesis.

RUNX3 site-specific hypermethylation predicts papillary thyroid cancer recurrence.

Papillary thyroid cancer (PTC) is the most common epithelial thyroid tumor, accounting for more than 80% of all thyroid cancers. Although PTC shows an indolent character and excellent prognosis, patients with aggressive characteristics are more likely to have a disease recurrence and die in the end. The aim of this study was to analyze BRAF(V600E) mutation and methylation levels of CpG sites in the promoters of CDH1, DAPK, RARβ and RUNX3 genes in a cohort of PTCs, and investigate their association with tumor recurrence.

Epithelial cell-derived periostin functions as a tumor suppressor in gastric cancer through stabilizing p53 and E-cadherin proteins via the Rb/E2F1/p14ARF/Mdm2 signaling pathway.

Periostin is usually considered as an oncogene in diverse human cancers, including breast, prostate, colon, esophagus, and pancreas cancers, whereas it acts as a tumor suppressor in bladder cancer. In gastric cancer, it has been demonstrated that periglandular periostin expression is decreased whereas stromal periostin expression is significantly increased as compared with normal gastric tissues. Moreover, periostin produced by stromal myofibroblasts markedly promotes gastric cancer cell growth.

Pathogenetic mechanisms in gastric cancer.

Gastric cancer (GC) is a major public health issue as the fourth most common cancer and the second leading cause of cancer-related death. Recent advances have improved our understanding of its molecular pathogenesis, as best exemplified by elucidating the fundamental role of several major signaling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these signaling pathways, such as gene mutations, copy number variants, aberrant gene methylation and histone modification, nucleosome positioning, and microRNAs.

Association between bone marrow dosimetric parameters and acute hematologic toxicity in cervical cancer patients undergoing concurrent chemoradiotherapy: comparison of three-dimensional conformal radiotherapy and intensity-modulated radiation therapy.

Objective: We compare different dosimetric parameters in cervical cancer patients receiving concurrent chemotherapy and three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT) and explore the incidence of hematological toxicity (HT) in these patients.

Methods: Twenty patients receiving 3DCRT or IMRT and 4 weekly doses of cisplatin (25 mg/m/w) were studied. The volumes of bone marrow receiving 10, 20, 30, 40 and 50 Gy or greater (V10, V20, V30, V40, and V50, respectively) were calculated.

Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats.

We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar-Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions.

[Expressions of FOXC1 and MMP-7 in molecular subtypes of breast cancer and their association with clinicopathological characteristics].

Objective: To investigate the expressions of FOXC1 and matrix metalloproteinase 7 (MMP-7) in different molecular subtypes of breast cancer and their association with clinicopathological characteristics of the disease.

Methods: Based on immunohistochemical results of ER, PR, HER2, CK5/6, CK14 and EGFR, 105 breast cancer patients were classified as 4 subtypes: luminal, HER2 positive, basal-like subtype (BLs) and normal breast-like subtype (NBLs). The association of FOXC1 and MMP-7 expressions with clinicopathological parameters in different molecular subtypes was analyzed.

Catheter-directed thrombolysis in the treatment of acute deep venous thrombosis: a meta-analysis.

We performed a meta-analysis for systematic evaluation of the status quo of catheter thrombolysis for the treatment of acute lower limb deep vein thrombosis in China. We searched the China Biomedical bibliographic database (CBM), China National Knowledge Infrastructure (CNKI), Weipu full-text electronic journals, Wanfang full-text database, and Medline (1990 through June 2011) for clinical randomized controlled trials of catheter-directed thrombolysis and superficial venous thrombolysis to compare their efficacies for the treatment of acute deep vein thrombosis. The results were analyzed by using the Cochrane-recommended RevMan 4.

Necrolytic migratory erythema as the first manifestation of pancreatic neuroendocrine tumor.

Necrolytic migratory erythma (NME) is an obligatory paraneoplastic syndrome. Here we describe a woman admitted to the dermatology ward with NME which was later found to be associated with glucagonoma, a slow-growing, rare pancreatic neuroendocrine tumor. Even more rarely, the tumor was located in the pancreas head, while most of such lesions are located in the distal pancreas.

Muscarinic receptor activation increases hERG channel expression through phosphorylation of ubiquitin ligase Nedd4-2.

The human ether-à-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel, which is important for cardiac repolarization. Reduction of hERG current due to genetic mutations or drug interferences causes long QT syndrome, leading to cardiac arrhythmias and sudden death. To date, there is no effective therapeutic method to restore or enhance hERG channel function.

ZIC1 is a putative tumor suppressor in thyroid cancer by modulating major signaling pathways and transcription factor FOXO3a.

Context: ZIC1 has been reported to be overexpressed and plays an oncogenic role in some brain tumors, whereas it is inactivated by promoter hypermethylation and acts as a tumor suppressor in gastric and colorectal cancers. However, until now, its biological role in thyroid cancer remains totally unknown.

Objectives: The aim of this study is to explore the biological functions and related molecular mechanism of ZIC1 in thyroid carcinogenesis.

Inherited defects in thyroid hormone cell-membrane transport and metabolism.

The description of two novel human defects in the last ten years has uncovered new aspects of thyroid hormone physiology with regard to cell-membrane transport and intracellular metabolism. Mutations in the X-linked monocarboxylate transporter 8 (MCT8) gene result in an invalidating neurodevelopmental phenotype in males and pathognomonic thyroid functions tests with high T3, low rT3, low or low normal T4, and normal or slightly high TSH. Recessive mutations in the selenocysteine insertion sequence binding protein 2 (SBP2) gene present a variable clinical phenotype depending on the severity of the defect and its consequences on the selenoprotein hierarchy.

Analysis of BRAF(V600E) mutation and DNA methylation improves the diagnostics of thyroid fine needle aspiration biopsies.

Background: Thyroid nodules with indeterminate cytological features on fine needle aspiration biopsy specimens (FNABs) have a ~20% risk of thyroid cancer. BRAF(V600E) mutation and DNA methylation are useful markers to distinguish malignant thyroid neoplasm from benign. The aim of this study was to determine whether combined detection of BRAF(V600E) mutation and methylation markers on FNABs could improve the diagnostic accuracy of thyroid cancer.

Inactivation of von Hippel-Lindau increases ovarian cancer cell aggressiveness through the HIF1α/miR-210/VMP1 signaling pathway.

The inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene not only results in tumor initiation, but also mediates tumor metastasis. However, the mechanisms by which VHL inactivation leads to metastasis have not yet been well defined. In this study, the silencing of VHL in 3AO and SKOV3 ovarian cancer cells was found to promote cell motility and to increase the expression of matrix metalloproteinase (MMP)2, MMP9, hypoxia-inducible factor 1-α (HIF-1α) and microRNA (miR)-210.

Low copy number of mitochondrial DNA (mtDNA) predicts worse prognosis in early-stage laryngeal cancer patients.

Objectives: Alterations in mitochondrial DNA (mtDNA) copy number have been widely reported in various human cancers, and been considered to be an important hallmark of cancers. However, little is known about the value of copy number variations of mtDNA in the prognostic evaluation of laryngeal cancer.

Design And Methods: Using real-time quantitative PCR method, we investigated mtDNA copy number in a cohort of laryngeal cancers (n =204) and normal laryngeal tissues (n =40), and explored the association of variable mtDNA copy number with clinical outcomes of laryngeal cancer patients.

Associations between Fas/FasL polymorphisms and susceptibility to cervical cancer: a meta-analysis.

Unlabelled: Genetic polymorphisms in the Fas/Fas ligand (FasL) gene were proposed to be associated with susceptibility to cervical cancer, but previous studies reported controversial findings. We performed a meta-analysis to assess the associations between Fas/FasL polymorphisms and susceptibility to cervical cancer. We carried out a literature search in PubMed and Embase databases for studies on the associations between Fas/FasL polymorphisms and susceptibility to cervical cancer.