Who Should Undergo Chronic Total Occlusion Percutaneous Coronary Intervention? The EXPLORation Continues ∗

Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has been growing by leaps and bounds in recent years, fueled by advances in techniques, equipment, and underpinning clinical evidence (1). A major gap, however, has been the lack of randomized controlled trials comparing CTO PCI with medical therapy (2).

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Veterans Affairs Health Care System as Cardiology Training Site A Fellow’s Perspective

A majority of cardiology fellows receive at least part of their training at the Veterans Affairs Health Administration (VHA) hospitals and clinics. In this paper, we discuss the unique role and challenges of advanced cardiology training at the VHA from the fellow's perspective. Finally, we explore the potential improvements and future directions of cardiology training at the VHA, which will have a significant effect on future generation of cardiologists.

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Late Outcomes of Transcatheter Aortic Valve Replacement in High-Risk Patients The FRANCE-2 Registry

Background

Transcatheter aortic valve replacement (TAVR) has revolutionized management of high-risk patients with severe aortic stenosis. However, survival and the incidence of severe complications have been assessed in relatively small populations and/or with limited follow-up.

Objectives

This report details late clinical outcome and its determinants in the FRANCE-2 (FRench Aortic National CoreValve and Edwards) registry.

Methods

The FRANCE-2 registry prospectively included all TAVRs performed in France. Follow-up was scheduled at 30 days, at 6 months, and annually from 1 to 5 years. Standardized VARC (Valve Academic Research Consortium) outcome definitions were used.

Results

A total of 4,201 patients were enrolled between January 2010 and January 2012 in 34 centers. Approaches were transarterial (transfemoral 73%, transapical 18%, subclavian 6%, and transaortic or transcarotid 3%) or, in 18% of patients, transapical. Median follow-up was 3.8 years. Vital status was available for 97.2% of patients at 3 years. The 3-year all-cause mortality was 42.0% and cardiovascular mortality was 17.5%. In a multivariate model, predictors of 3-year all-cause mortality were male sex (p Conclusions

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Lipid Measurements Fasting or Nonfasting, Women or Men

I read the article by Driver et al. (1), which was recently published in the Journal, with great interest. The investigators reported that to assess the initial risk of atherosclerotic cardiovascular disease in an untreated patient, fasting or nonfasting total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels provide all that is required. Among those with a nonfasting non–HDL-C level ≥220 mg/dl, a familial cause of hyperlipidemia should be suspected and evaluated further (1).

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TAVR Prognosis, Aging, and the Second TAVR Tsunami Insights From France ∗

The early results of the French national transcatheter aortic valve implantation registry, FRANCE 2 (FRench Aortic National CoreValve and Edwards registry), were reported previously (1). The initial report of FRANCE 2 identified the need for safer and more effective technology to reduce the need for alternative access and the high rates of paravalvular leakage. The current publication in this issue of the Journal includes longer-term outcomes of 4,201 patients treated at all sites in France from January 2010 to January 2012 (2). The registry has multiple positive attributes including use of a clinical events committee to adjudicate the cause of mortality.

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The Supply and Demand of the Cardiovascular Workforce Striking the Right Balance

As the burden of cardiovascular disease in the United States continues to increase, uncertainty remains on how well-equipped the cardiovascular workforce is to meet the challenges that lie ahead. In a time when health care is rapidly shifting, numerous factors affect the supply and demand of the cardiovascular workforce. This Council Commentary critically examines several factors that influence the cardiovascular workforce. These include current workforce demographics and projections, evolving health care and practice environments, and the increasing burden of cardiovascular disease. Finally, we propose 3 strategies to optimize the workforce. These focus on cardiovascular disease prevention, the effective utilization of the cardiovascular care team, and alterations to the training pathway for cardiologists.

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Mechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy Insights From Wave Intensity Analysis and Magnetic Resonance

Background

Angina is common in hypertrophic cardiomyopathy (HCM) and is associated with abnormal myocardial perfusion. Wave intensity analysis improves the understanding of the mechanics of myocardial ischemia.

Objectives

Wave intensity analysis was used to describe the mechanisms underlying perfusion abnormalities in patients with HCM.

Methods

Simultaneous pressure and flow were measured in the proximal left anterior descending artery in 33 patients with HCM and 20 control patients at rest and during hyperemia, allowing calculation of wave intensity. Patients also underwent quantitative first-pass perfusion cardiac magnetic resonance to measure myocardial perfusion reserve.

Results

Patients with HCM had a lower coronary flow reserve than control subjects (1.9 ± 0.8 vs. 2.7 ± 0.9; p = 0.01). Coronary hemodynamics in HCM were characterized by a very large backward compression wave during systole (38 ± 11% vs. 21 ± 6%; p Conclusions

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Preparing for a Value-Based Health Care System

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Cardiac-Coronary Coupling ∗

The coronary circulation is unique among vascular beds, as myocardial perfusion depends not only on aortic pressure, conduit artery patency, and microvascular resistance but also on the dynamic interaction between myocardium and microvasculature during the cardiac cycle. As a result of phasic compression and decompression of intramyocardial vessels by surrounding myocytes, coronary flow is intimately linked to myocardial relaxation and contraction, a process known as cardiac–coronary coupling.

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Transcatheter Aortic Valve Replacement to Treat Pure Aortic Regurgitation on Noncalcified Native Valves

No evidence exists on the feasibility of transcatheter aortic valve replacement (TAVR) using balloon-expandable valves to treat pure aortic regurgitation (AR) on noncalcified native valves (NCNV). We report the first experience of TAVR with SAPIEN 3 prostheses (Edwards Lifesciences, Irvine, California) in patients with pure AR on NCNV.

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Carbamylated Low-Density Lipoproteins Induce a Prothrombotic State Via LOX-1 Impact on Arterial Thrombus Formation In Vivo

Background

Carbamylation alters low-density lipoprotein (LDL) structure and is thought to promote vascular inflammation and dysfunction in patients with chronic kidney disease (CKD).

Objectives

This study sought to determine whether carbamylated LDL (cLDL) exerts prothrombotic effects in vascular cells and platelets and whether cLDL enhances arterial thrombus formation in vivo.

Methods

LDL was isolated from healthy subjects or patients with CKD by sequential ultracentrifugation. Ex vivo carbamylation of LDL from healthy subjects was induced with potassium cyanate. Arterial thrombus formation was analyzed in a murine carotid artery photochemical injury model. Protein expression and mRNA levels were analyzed by Western blotting, flow cytometry, and real-time PCR. Platelet aggregation was measured by impedance aggregometry.

Results

Intravenous administration of cLDL in mice accelerated arterial thrombus formation compared to treatment with native LDL (nLDL) or vehicle. Tissue lysates of mouse carotid arteries revealed that cLDL induced the expression of TF, PAI-1, and LOX-1 mRNA in vascular cells. In human aortic smooth muscle and endothelial cells, cLDL induced TF and PAI-1 expression. In contrast, nLDL had no effect on either cell type. While nLDL and cLDL had no aggregatory effect on resting platelets, cLDL enhanced platelet aggregation in response to different agonists. This effect was mediated by mitogen-activated protein kinase p38 phosphorylation and LOX-1 translocation to the surface. LDL isolated from patients with CKD mimicked the prothrombotic effects of cLDL on vascular cells, platelets, and thrombus formation in vivo.

Conclusions

We found that cLDL induces prothrombotic effects in vascular cells and platelets by activation of the LOX-1 receptor and enhances thrombus formation in vivo. This observation reveals a new mechanism underlying the increased incidence of acute thrombotic events observed in patients with CKD and may lead to the development of new lipid-targeting therapies in this population.

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Takotsubo Cardiomyopathy Outcomes Should Be Stratified Based on the Triggering Etiology

The study by Tornvall et al. (1) published in a recent issue of the Journal showed an increased mortality risk associated with Takotsubo cardiomyopathy (TC). After multivariate adjustment for coronary artery disease risk factors and risk markers for TC, the mortality rates were comparable among patients with TC and acute coronary syndrome (ACS). However, one of the major limitations was that the study failed to subdivide the patients of TC into its primary and secondary forms. Primary TC occurs in the setting of emotional or psychic stimuli or no identifiable triggers (idiopathic), whereas secondary TC is triggered by physical stressors such as sepsis, intracranial hemorrhage or cerebrovascular accident, trauma, surgery, or other critical illnesses (2). Secondary TC is associated with much worse short- and long-term prognoses (2). Primary TC, in comparison, generally has a benign spectrum and a good overall prognosis, unless complicated by cardiogenic shock. In a large recent study that used the RETAKO National Registry (Spanish REgistry for TAKOtsubo cardiomyopathy), the patients were divided into primary and secondary TC cohorts, who had otherwise similar demographic, functional, and cardiovascular risk profiles (2). Those with secondary TC had significantly increased mortality rates (hazard ratio: 3.41; 95% confidence interval: 1.14 to 10.16; p = 0.02), recurrences, and a composite of all-cause death, recurrence, and readmission rates due to cardiovascular causes. There were also higher rates of cardiogenic shock, peak creatine kinase levels, and increased use of inotropes and mechanical ventilation in the secondary TC cohort. Thus, the general conclusion of the current study led by Tornvall et al. that patients with TC and ACS have a similar prognosis should be perceived with caution. This is because many patients with secondary TC have increased morbidity and mortality due an alternate primary insult and/or cause. If the investigators could provide a subanalysis based on the etiology of TC (primary vs. secondary), it would be significantly valuable and would serve as a validation or refutation of this concept. Treatment approaches may also need to be tailored based on the presentation, with secondary TC forms needing more intensive monitoring and management.

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Carbamylated Low-Density Lipoprotein and Thrombotic Risk in Chronic Kidney Disease ∗

Carbamylation is a form of post-translational modification in which cyanate/isocyanate covalently modifies nucleophilic groups on proteins (e.g., N-terminal and Ne-amine groups of lysine residues or thiol group of cysteine residues), forming a carbamyl group (1). Historically, carbamylation was believed to predominantly be fostered by uremia. This is because urea is in equilibrium with cyanate/isocyanate, and carbamylation of proteins dramatically increases with severe impairment in renal function (1). Recent studies also discovered a second pathway for generation of the reactive cyanate/isocyanate species and protein carbamylation-leukocyte heme peroxidases like myeloperoxidase (MPO) (2). MPO can use plasma levels of thiocyanate as a cosubstrate to generate cyanate and catalyze protein carbamylation. Because plasma levels of thiocyanate are heightened in smokers and in exposure to second-hand or work-place smoke, this pathway has been linked to heightened cardiovascular disease risks in subjects who smoke (2). MPO has been shown to catalyze protein carbamylation at sites of inflammation, such as within the atherosclerotic artery wall where MPO-catalyzed oxidative processes are enhanced (2). Elevated levels of carbamylated proteins in plasma or serum are associated with adverse prognosis, including enhanced mortality rate in stable cardiac patients (2), subjects with end- stage renal disease on hemodialysis (3), and in patients with chronic heart failure (4).

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Reply Lipid Measurements: Fasting or Nonfasting, Women or Men

We appreciate Dr. Cerit's thoughtful comments on our recent article. We agree with his belief that individual patient characteristics should be carefully considered when deciding whether to order fasting or nonfasting lipids. This is one purpose of the patient–clinician risk discussion as outlined in the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines (1).

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Contents/Barcode

Publication date: November 2016
Source:Magnetic Resonance Imaging, Volume 34, Issue 9





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Editorial Board

Publication date: November 2016
Source:Magnetic Resonance Imaging, Volume 34, Issue 9





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Comments on “Prediction of low-risk breast cancer using perfusion parameters and apparent diffusion coefficient”

Publication date: November 2016
Source:Magnetic Resonance Imaging, Volume 34, Issue 9
Author(s): Li Xu




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Reply to “Breast MRI background parenchymal enhancement (BPE) correlates with the risk of breast cancer”

Publication date: November 2016
Source:Magnetic Resonance Imaging, Volume 34, Issue 9
Author(s): Barbara Bennani-Baiti, Pascal A. Baltzer




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Reply to letter by Dyverfeldt and Ebbers regarding the article “Estimation of turbulent kinetic energy using 4D phase-contrast MRI: Effect of scan parameters and target vessel size”

Publication date: November 2016
Source:Magnetic Resonance Imaging, Volume 34, Issue 9
Author(s): Hojin Ha, Dongha Hwang, Guk Bae Kim, Jihoon Kweon, Sang Joon Lee, Jehyun Baek, Young-Hak Kim, Namkug Kim, Dong Hyun Yang




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Imipramine ameliorates early life stress-induced alterations in synaptic plasticity in the rat lateral amygdala

Publication date: 15 January 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 317
Author(s): Joanna Danielewicz, Aleksandra Trenk, Grzegorz Hess
Long-term potentiation (LTP) and long-term depression (LTD) are two opposite forms of synaptic plasticity at the cortical and thalamic inputs to the lateral amygdala (LA). It has been demonstrated that maternal separation (MS) of rat pups results in alterations in the potential for both pathways to undergo LTP and LTD in adolescence. Imipramine, a prototypic tricyclic antidepressant, has been shown to counteract some detrimental effects of MS on rat behavior, however it is not known whether MS-induced alterations in the potential for bidirectional synaptic plasticity in the LA could be reversed by imipramine treatment. To this end, rat pups were subjected to MS (3h/day) on postnatal days (PNDs) 1–21. On each of PNDs 29–42, male rats previously subjected to MS were injected subcutaneously with imipramine (10mg/kg). Field potentials were recorded ex vivo from slices containing the LA and saturating levels of LTP and LTD were induced. At the thalamic input to the LA, both the maximum LTP and the maximum LTD were reduced in rats subjected to MS when compared to control animals, confirming earlier results. However, these effects were no longer present in rats subjected to MS and later treated with imipramine. At the cortical input in slices prepared from MS-subjected rats, an impairment of the maximum LTP and an enhancement of the maximum LTD were observed. At the cortical input in rats subjected to MS and receiving imipramine treatment, the level of LTD was comparable to control but imipramine did not restore the potential for LTP at this input. These results demonstrate that imipramine fully reverses the effects of MS in the thalamo-amygdalar pathway, however, in the cortico-amygdalar pathway the reversal of the effects of MS by imipramine is partial.



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Prefrontal cortical activity associated with visual stimulus categorization in non-human primates measured with near-infrared spectroscopy

Publication date: 15 January 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 317
Author(s): Young-A Lee, Valentine Pollet, Akemi Kato, Yukiori Goto
In biomedical research of brain dysfunction in psychiatric disorders, utilization of animal models is essential. However, translation of findings in animal models into the realm of human clinical conditions requires reliable biomarkers that are assessed with the methods mutually employed in animal models and human patients. Near-infrared spectroscopy (NIRS) is a functional neuroimaging technique that has now been widely utilized in human basic and clinical research. However, its application to animal models has been barely conducted. In this study, we developed the method to measure neural activity in the cortex of Japanese macaques using NIRS, and examined cortical responses to presentation of a set of visual stimuli that were categorized into four different groups (flower, monkey, snake, food). Prefrontal cortical (PFC) oxy- and deoxy-hemoglobin changes were found to reliably distinguish the categories of these visual stimuli. The results suggest that cortical activity measurement with NIRS in primates can be a valuable model for identifying biomarkers associated with psychiatric disorders.



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Concurrent Chemotherapy Based on Genetic Testing in Patients With High-Risk Salivary Gland Tumors

Conditions:   Salivary Gland Tumors;   Head and Neck Cancer
Interventions:   Drug: Docetaxel;   Radiation: Intensity-modulated radiotherapy;   Drug: Pemetrexed;   Drug: Cisplatin
Sponsor:   Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Recruiting - verified September 2016

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ReIrradiation With FDG-PET Guided Dose Painting

Condition:   Recurrent and Second Primary Head and Neck Cancer
Intervention:   Radiation: FDG-PET guided dose painting
Sponsors:   Oslo University Hospital;   Norwegian Cancer Society
Recruiting - verified September 2016

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Participatory Research for Fine-tuning of a 2.0 System to Optimise Home Management of Oral Cancer Therapies.

Conditions:   Cancer;   Oral Drug Administration
Intervention:   Device: TreC-Onco
Sponsors:   Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori;   Kessler Foundation
Recruiting - verified September 2016

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Scholar : Oncology Reports - Volume:36 Number:4

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TABLE OF CONTENTS October 2016 Volume 36 Issue 4

Current treatments for advanced melanoma and introduction of a promising novel gene therapy for melanoma (Review) Jae‑Rim Heo, Nam‑Hyung Kim, Jaejin Cho, Kyung‑Chul Choi View Abstract ❯

Parathyroid hormone/parathyroid hormone-related peptide regulate osteosarcoma cell functions: Focus on the extracellular matrix (Review) Dragana Nikitovic, Rafaela‑Maria Kavasi, Aikaterini Berdiaki, Dionysios Papachristou, John Tsiaoussis, Demetrios Spandidos, Aristides Tsatsakis, George Tzanakakis View Abstract ❯

RNAi-mediated HOXD3 knockdown inhibits growth in human RKO cells Fangjun Chen, Guoping Sun, Jun Peng View Abstract ❯

Schisandrin B inhibits cell proliferation and induces apoptosis in human cholangiocarcinoma cells Xiaohui Yang, Shuai Wang, Yunchuan Mu, Yixiong Zheng View Abstract ❯

Crosstalk between Beclin-1-dependent autophagy and caspase‑dependent apoptosis induced by tanshinone IIA in human osteosarcoma MG-63 cells Kun Ma, Chuan Zhang, Man-Yu Huang, Yan-Xing Guo, Guo-Qiang Hu View Abstract ❯

PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN Jianbo Xiong, Zhengrong Li, Yang Zhang, Daojiang Li, Guoyang Zhang, Xianshi Luo, Zhigang Jie, Yi Liu, Yi Cao, Zhibiao Le, Shengxing Tan, Wenyu Zou, Peitao Gong, Lingyu Qiu, Yuanyuan Li, Huan Wang, Heping Chen View Abstract ❯

PTK7 overexpression in colorectal tumors: Clinicopathological correlation and prognosis relevance Xiuyun Tian, Liang Yan, Donghai Zhang, Xiaoya Guan, Bin Dong, Min Zhao, Chunyi Hao View Abstract ❯

TGF-β1 regulating miR-205/miR-195 expression affects the TGF-β signal pathway by respectively targeting SMAD2/SMAD7 Yingjun Duan, Qianxue Chen View Abstract ❯

Circulating tumour cells as biomarkers for evaluating cryosurgery on unresectable hepatocellular carcinoma Jian Shi, Yuan Li, Shuzhen Liang, Jianying Zeng, Guifeng Liu, Feng Mu, Haibo Li, Jibing Chen, Mao Lin, Shihou Sheng, Huaiyu Zhang, Tongjun Liu, Lizhi Niu View Abstract ❯

Decreased LIPF expression is correlated with DGKA and predicts poor outcome of gastric cancer Yi Kong, Yan Zheng, Yanfei Jia, Ping Li, Yunshan Wang View Abstract ❯

Next generation deep sequencing identified a novel lncRNA n375709 associated with paclitaxel resistance in nasopharyngeal carcinoma Shuling Ren, Guo Li, Chao Liu, Tao Cai, Zongwu Su, Ming Wei, Li She, Yongquan Tian, Yuanzheng Qiu, Xin Zhang, Yong Liu, Yunyun Wang View Abstract ❯

Expression pattern and methylation of estrogen receptor α in breast intraductal proliferative lesions Xiaoyun Mao, Zhen Qiao, Chuifeng Fan, Ayao Guo, Xinmiao Yu, Feng Jin View Abstract ❯

Combination of the histone deacetylase inhibitor depsipeptide and 5-fluorouracil upregulates major histocompatibility complex class II and p21 genes and activates caspase-3/7 in human colon cancer HCT-116 cells Kouji Okada, Shuko Hakata, Jun Terashima, Toshie Gamou, Wataru Habano, Shogo Ozawa View Abstract ❯

Ultrasound-targeted microbubble destruction of calcium channel subunit α 1D siRNA inhibits breast cancer via G protein-coupled receptor 30 Yanlei Ji, Zhen Han, Limei Shao, Yuehuan Zhao View Abstract ❯

Metastasis-associated protein is a predictive biomarker for metastasis and recurrence in gastric cancer Yoshinaga Okugawa, Yasuhiko Mohri, Koji Tanaka, Mikio Kawamura, Susumu Saigusa, Yuji Toiyama, Masaki Ohi, Yasuhiro Inoue, Chikao Miki, Masato Kusunoki View Abstract ❯

High expression of miR-15b predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy Wen-Bin Ji, Xin Liu, Ying Luo, Wen-Zhi Zhang View Abstract ❯

Exogenous hydrogen sulfide exerts proliferation, anti-apoptosis, migration effects and accelerates cell cycle progression in multiple myeloma cells via activating the Akt pathway Dong Zheng, Ziang Chen, Jingfu Chen, Xiaomin Zhuang, Jianqiang Feng, Juan Li View Abstract ❯

miR-145 suppresses colorectal cancer cell migration and invasion by targeting an ETS-related gene Shuling Li, Xiaobing Wu, Yuandong Xu, Shangbiao Wu, Zhifa Li, Rong Chen, Nanqi Huang, Ziyuan Zhu, Xuehu Xu View Abstract ❯

RUNX3 plays an important role in As2O3‑induced apoptosis and allows cells to overcome MSC‑mediated drug resistance Guo‑Zheng Pan, Feng‑Xian Zhai, Yin Lu, Zhi‑Gang Fang, Rui‑Fang Fan, Xiang‑Fu Liu, Dong‑Jun Lin View Abstract ❯

Suppression of CEP55 reduces cell viability and induces apoptosis in human lung cancer Ligang Liu, Qi Mei, Jing Zhao, Yuhong Dai, Qiang Fu View Abstract ❯

Cortactin promotes cell migration and invasion through upregulation of the dedicator of cytokinesis 1 expression in human colorectal cancer Xiaoqian Jing, Huo Wu, Xiaopin Ji, Haoxuan Wu, Minmin Shi, Ren Zhao View Abstract ❯

An integrin αvβ3 antagonistic modified peptide inhibits tumor growth through inhibition of the ERK and AKT signaling pathways Lirong Hu, Jingjing Wang, Ying Wang, Hanmei Xu View Abstract ❯

Fucoidan inhibits angiogenesis induced by multiple myeloma cells Fen Liu, Guoping Luo, Qing Xiao, Liping Chen, Xiaohua Luo, Jinglong Lv, Lixue Chen View Abstract ❯

Downregulation of DNA-PKcs suppresses P-gp expression via inhibition of the Akt/NF-κB pathway in CD133-positive osteosarcoma MG-63 cells Ka Li, Xin Li, Jiguang Tian, Hongliang Wang, Jingbo Pan, Jianmin Li View Abstract ❯

Expression status of cyclase‑associated protein 2 as a prognostic marker for human breast cancer Lihua Xu, Sida Peng, Qunai Huang, Yu Liu, Hua Jiang, Xi Li, Jiani Wang View Abstract ❯

JQ1, a small molecule inhibitor of BRD4, suppresses cell growth and invasion in oral squamous cell carcinoma Limei Wang, Xiuyin Wu, Ping Huang, Zhijun Lv, Yuping Qi, Xiujuan Wei, Pishan Yang, Fenghe Zhang View Abstract ❯

Membrane bile acid receptor TGR5 predicts good prognosis in ampullary adenocarcinoma patients with hyperbilirubinemia Min-Chan Chen, Yi-Ling Chen, Tzu-Wen Wang, Hui-Ping Hsu, Ming-Derg Lai View Abstract ❯

Oleuropein inhibits the proliferation and invasion of glioma cells via suppression of the AKT signaling pathway Ming Liu, Jian Wang, Bin Huang, Anjing Chen, Xingang Li View Abstract ❯

CCL22 and IL-37 inhibit the proliferation and epithelial-mesenchymal transition process of NSCLC A549 cells Yu-Hua Chen, Bi-Yun Zhou, Xian-Jing Wu, Jun-Fa Xu, Jun‑Ai Zhang, Yong-Hua Chen, Si-Si Liang View Abstract ❯

Acidic extracellular pH promotes prostate cancer bone metastasis by enhancing PC-3 stem cell characteristics, cell invasiveness and VEGF-induced vasculogenesis of BM-EPCs Sheng Huang, Yubo Tang, Xinsheng Peng, Xingdong Cai, Qingde Wa, Dong Ren, Qiji Li, Jiaquan Luo, Liangping Li, Xuenong Zou, Shuai Huang View Abstract ❯

Overexpression of long non-coding RNA MFI2 promotes cell proliferation and suppresses apoptosis in human osteosarcoma Zhixun Yin, Hongmei Ding, Erming He, Jingmhen Chen, Ming Li View Abstract ❯

MicroRNA-181d is a tumor suppressor in human esophageal squamous cell carcinoma inversely regulating Derlin-1 Dejun Li, Mo Shi, Hongsheng Ji, Gang Chen, Hua Jiang, Zhou Wang View Abstract ❯

miR-451 suppresses bladder cancer cell migration and invasion via directly targeting c-Myc Jun Wang, Xiaomei Zhao, Jianhua Shi, Yiwei Pan, Qinghai Chen, Pengfei Leng, Yan Wang View Abstract ❯

Anticancer effect of 20(S)-ginsenoside Rh2 on HepG2 liver carcinoma cells: Activating GSK-3β and degrading β-catenin Qingqiang Shi, Xueping Shi, Gei Zuo, Wei Xiong, Haixing Li, Pei Guo, Fen Wang, Yi Chen, Jing Li, Di‑Long Chen View Abstract ❯

Depletion of SENP1 suppresses the proliferation and invasion of triple-negative breast cancer cells Zhonghua Wang, Jia Jin, Jian Zhang, Leiping Wang, Jun Cao View Abstract ❯

MicroRNA-19b inhibits proliferation of gastric cancer cells by targeting B-cell CLL/lymphoma 3 Huan Wang, Mei Xiong, Yongwu Hu, Yusheng Sun, Qing Ma View Abstract ❯

AKT1 as the PageRank hub gene is associated with melanoma and its functional annotation is highly related to the estrogen signaling pathway that may regulate the growth of melanoma Jingjing Zhao, Xue Zeng, Ping Song, Xiaohong Wu, Hongbo Shi View Abstract ❯

Casticin induces DNA damage and inhibits DNA repair-associated protein expression in B16F10 mouse melanoma cancer cells Yung-Luen Shih, Jason Chou, Ming-Yang Yeh, Hsiao-Min Chou, Hsiu-Chen Chou, Hsu-Feng Lu, Hung-Sheng Shang, Fu-Shin Chueh, Yung-Lin Chu, Shu-Ching Hsueh, Jing-Gung Chung View Abstract ❯

Overexpression of microRNA-497 suppresses cell proliferation and induces apoptosis through targeting paired box 2 in human ovarian cancer Zhong Lin, Junling Zhao, Xindan Wang, Xuehong Zhu, Liansheng Gong View Abstract ❯

Epigenetically deregulated miR-200c is involved in a negative feedback loop with DNMT3a in gastric cancer cells Yingfei Li, Yuqiang Nie, Sanfang Tu, Hong Wang, Yongjian Zhou, Yanlei Du, Jie Cao, Min Ye View Abstract ❯

Clinical significance of α‑ and β‑Klotho in urothelial carcinoma of the bladder Shunta Hori, Makito Miyake, Sayuri Onishi, Yoshihiro Tatsumi, Yosuke Morizawa, Yasushi Nakai, Satoshi Anai, Nobumichi Tanaka, Kiyohide Fujimoto View Abstract ❯

An efficient and simple co-culture method for isolating primary human hepatic cells: Potential application for tumor microenvironment research Wei Dong, Aiguo Lu, Jingkun Zhao, Shuai Yin, Baochi Ou, Hao Feng View Abstract ❯

MicroRNA-106a regulates phosphatase and tensin homologue expression and promotes the proliferation and invasion of ovarian cancer cells Liang Chen, Fang Zhang, Xiu-Gui Sheng, Shi-Qian Zhang, Yue-Ting Chen, Bo-Wen Liu View Abstract ❯

Genome-wide profiling of chemoradiation‑induced changes in alternative splicing in colon cancer cells Wei Xiong, Depei Gao, Yunfeng Li, Xin Liu, Peiling Dai, Jiyong Qin, Guanshun Wang, Kangming Li, Han Bai, Wenhui Li View Abstract ❯

Knockdown of FOXK1 alone or in combination with apoptosis-inducing 5-FU inhibits cell growth in colorectal cancer Yao Wu, Ruyi Xie, Xuehua Liu, Jing Wang, Ying Peng, Weimei Tang, Meiyan Wu, Pei Zhang, Yang Ba, Jinjun Zhao, Aimin Li, Qingzhen Nan, Ye Chen, Side Liu, Jide Wang View Abstract ❯

Nitidine chloride inhibits the malignant behavior of human glioblastoma cells by targeting the PI3K/AKT/mTOR signaling pathway Ming Liu, Jiwei Wang, Qichao Qi, Bin Huang, Anjing Chen, Xingang Li, Jian Wang View Abstract ❯

miR-15a induces cell apoptosis by targeting BCL2L2 and BCL2 in HPV-positive hypopharyngeal squamous cell carcinoma Wuhao Lu, Long Feng, Yan Zhang, Yunyun Ma, Ping Li, Yuanyuan Wang, Yuwen Du, Xiaonan Chen, Shujun Wu, Guoqiang Zhao, Weihua Lou View Abstract ❯

miR-17 inhibits ovarian cancer cell peritoneal metastasis by targeting ITGA5 and ITGB1 Cheng Gong, Zongyuan Yang, Fenghua Wu, Lintao Han, Yi Liu, Wei Gong View Abstract ❯

Clinical effects of miR-101 on prognosis of hepatocellular carcinoma and carcinogenic mechanism of anti-miR-101 Xuecheng Lv, Jinghua Li, Bingnan Yang View Abstract ❯

Increased NEK2 in hepatocellular carcinoma promotes cancer progression and drug resistance by promoting PP1/Akt and Wnt activation Sailan Wen, Yuwu Liu, Manyi Yang, Keda Yang, Jianghai Huang, Deyun Feng View Abstract ❯

Combination of nadroparin with radiotherapy results in powerful synergistic antitumor effects in lung adenocarcinoma A549 cells Xibing Zhuang, Tiankui Qiao, Guoxiong Xu, Sujuan Yuan, Qi Zhang, Xue Chen View Abstract ❯

Curcumin causes DNA damage and affects associated protein expression in HeLa human cervical cancer cells Hung-Sheng Shang, Chuan-Hsun Chang, Yu-Ru Chou, Ming-Yang Yeh, Man-Kuan Au, Hsu-Feng Lu, Yung-Lin Chu, Hsiao-Min Chou, Hsiu-Chen Chou, Yung-Luen Shih, Jing-Gung Chung View Abstract ❯

RLIP76 increases apoptosis through Akt/mTOR signaling pathway in gastric cancer Wenwen Wang, Juan Liu, Jianni Qi, Junyong Zhang, Qiang Zhu, Chengyong Qin View Abstract ❯

Methylation of the SEPT9_v2 promoter as a novel marker for the detection of circulating tumor DNA in breast cancer patients Saki Matsui, Naofumi Kagara, Chieko Mishima, Yasuto Naoi, Masafumi Shimoda, Atsushi Shimomura, Kenzo Shimazu, Seung Kim, Shinzaburo Noguchi View Abstract ❯

The diagnostic value and functional roles of phosphoglycerate mutase 1 in glioma Zhenkuan Xu, Jie Gong, Chuanwei Wang, Yunyan Wang, Yan Song, Wenzhe Xu, Zhiguo Liu, Yuguang Liu View Abstract ❯

Curcumin inhibits H2O2-induced invasion and migration of human pancreatic cancer via suppression of the ERK/NF-κB pathway Lei Cao, Jiangbo Liu, Lun Zhang, Xue Xiao, Wei Li View Abstract ❯

Identification of CD200+ colorectal cancer stem cells and their gene expression profile Shan-Shan Zhang, Zai-Wei Huang, Li-Xuan Li, Jin-Jin Fu, Bing Xiao View Abstract ❯

Thymoquinone induces apoptosis through downregulation of c-FLIP and Bcl-2 in renal carcinoma Caki cells Eun Park, Anil Chauhan, Kyoung-Jin Min, Dong Park, Taeg Kwon View Abstract ❯

Non-thermal gas plasma-induced endoplasmic reticulum stress mediates apoptosis in human colon cancer cells Madduma Ruwan Kumara, Mei Piao, Kyoung Kang, Yea Ryu, Jeong Park, Kristina Shilnikova, Jin Jo, Young Mok, Jennifer Shin, Yeonsoo Park, Seong Kim, Suk Yoo, Jin Hyun View Abstract ❯

Overexpression of CXCR7 induces angiogenic capacity of human hepatocellular carcinoma cells via the AKT signaling pathway Yuhui Chen, Fei Teng, Geying Wang, Zhiyu Nie View Abstract ❯

Foxp3 downregulation in NSCLC mediates epithelial-mesenchymal transition via NF-κB signaling Xi Wang, Ying Liu, Lingling Dai, Qi Liu, Liuqun Jia, Huan Wang, Lin An, Xiaogang Jing, Meng Liu, Pengfei Li, Zhe Cheng View Abstract ❯

Use of rhenium-188 for in vivo imaging and treatment of human cervical cancer cells transfected with lentivirus expressing sodium iodide symporter Min Zhang, Shuo Shi, Rui Guo, Yin Miao, Biao Li View Abstract ❯

Effects of an extract of Celtis aetnensis (Tornab.) Strobl twigs on human colon cancer cell cultures Rosaria Acquaviva, Valeria Sorrenti, Rosa Santangelo, Venera Cardile, Barbara Tomasello, Giuseppe Malfa, Luca Vanella, Andrea Amodeo, Carlo Genovese, Silvana Mastrojeni, Michela Pugliese, Monica Ragusa, Claudia Di Giacomo View Abstract ❯

HBx-induced miR-21 suppresses cell apoptosis in hepatocellular carcinoma by targeting interleukin-12 Dian Yin, Yilang Wang, Wenli Sai, Liang Zhang, Yajun Miao, Lili Cao, Xiaolu Zhai, Xiu Feng, Li Yang View Abstract ❯

MicroRNA-892b influences proliferation, migration and invasion of bladder cancer cells by mediating the p19ARF/cyclin D1/CDK6 and Sp-1/MMP-9 pathways Seung-Shick Shin, Sung-Soo Park, Byungdoo Hwang, Bokyung Moon, Won Kim, Wun-Jae Kim, Sung-Kwon Moon View Abstract ❯

MicroRNA-124 inhibits proliferation, invasion, migration and epithelial-mesenchymal transition of cervical carcinoma cells by targeting astrocyte-elevated gene-1 Xia Zhang, Dajun Cai, Lihua Meng, Bing Wang View Abstract ❯

MicroRNA-140 represses glioma growth and metastasis by directly targeting ADAM9 Xiaogang Liu, Shanjun Wang, Aiqin Yuan, Xunhui Yuan, Bing Liu View Abstract ❯

Overexpression of TRIB3 promotes angiogenesis in human gastric cancer Shaoting Dong, Jianling Xia, Hongqiang Wang, Li Sun, Zhenzhen Wu, Jianping Bin, Yulin Liao, Nailin Li, Wangjun Liao View Abstract ❯

Inhibition of FOXQ1 induces apoptosis and suppresses proliferation in prostate cancer cells by controlling BCL11A/MDM2 expression Xiang Zhang, Lijuan Wang, Yingmei Wang, Shenjia Shi, Huayu Zhu, Fengjin Xiao, Jing Yang, Angang Yang, Xiaoke Hao View Abstract ❯

Identification of brefelamide as a novel inhibitor of osteopontin that suppresses invasion of A549 lung cancer cells Jing Zhang, Osamu Yamada, Shinya Kida, Yoshihisa Matsushita, Shinya Murase, Toshio Hattori, Yuzuru Kubohara, Haruhisa Kikuchi, Yoshiteru Oshima View Abstract ❯

Epigenetic modulation of AR gene expression in prostate cancer DU145 cells with the combination of sodium butyrate and 5'-Aza-2'-deoxycytidine Barbora Fialova, Petra Luzna, Jan Gursky, Katerina Langova, Zdenek Kolar, Katerina Trtkova View Abstract ❯

miR‑1246 and miR‑4644 in salivary exosome as potential biomarkers for pancreatobiliary tract cancer Tatsuya Machida, Takaaki Tomofuji, Takayuki Maruyama, Toshiki Yoneda, Daisuke Ekuni, Tetsuji Azuma, Hisataka Miyai, Hirofumi Mizuno, Hironari Kato, Koichiro Tsutsumi, Daisuke Uchida, Akinobu Takaki, Hiroyuki Okada, Manabu Morita View Abstract ❯

Regulation of DEK expression by AP-2α and methylation level of DEK promoter in hepatocellular carcinoma Ming-Xu Qiao, Chun Li, Ai-Qun Zhang, Ling-Ling Hou, Juan Yang, Hong-Gang Hu View Abstract ❯

Upregulation of microRNA-34a enhances the DDP sensitivity of gastric cancer cells by modulating proliferation and apoptosis via targeting MET Zhandong Zhang, Ye Kong, Wei Yang, Fei Ma, Yonglei Zhang, Sheqing Ji, Er-Min Ma, Hongxing Liu, Yongshun Chen, Yawei Hua View Abstract ❯

miR-124 inhibits proliferation and invasion of human retinoblastoma cells by targeting STAT3 Shu Liu, Chunmei Hu, Yingxue Wang, Guang Shi, Yarong Li, Huang Wu View Abstract ❯

PIN1 in hepatocellular carcinoma is associated with TP53 gene status Jun Bae, Sang Noh, Kyoung Kim, Kyu Jang, Ho Park, Myoung Chung, Byung-Hyun Park, Woo Moon View Abstract ❯

miR-194 is a negative regulator of GEF-H1 pathway in melanoma Bingyu Guo, Qiang Hui, Yu Zhang, Peng Chang, Kai Tao View Abstract ❯

MicroRNA-106a suppresses proliferation, migration, and invasion of bladder cancer cells by modulating MAPK signaling, cell cycle regulators, and Ets-1-mediated MMP-2 expression Seung-Shick Shin, Sung-Soo Park, Byungdoo Hwang, Won Kim, Yung Choi, Wun-Jae Kim, Sung-Kwon Moon View Abstract ❯

6-8 October, 2016, Metropolitan Hotel, Athens, Greece 21st World Congress on Advances in Oncology & 19th International Symposium on Molecular Medicine

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mTOR inhibition mitigates molecular and biochemical alterations of vigabatrin-induced visual field toxicity in mice

Publication date: Available online 3 October 2016
Source:Pediatric Neurology
Author(s): Kara R. Vogel, Garrett R. Ainslie, Michelle A. Schmidt, Jonathan P. Wisor, K. Michael Gibson
PurposeGamma-vinyl-GABA (vigabatrin, VGB) is an antiepileptic drug and irreversible GABA transaminase inhibitor associated with visual field impairment which limits its clinical utility. Here, we sought to relate altered visual evoked potentials associated with VGB intake to transcriptional changes in the mTOR pathway and GABA receptors to expose further mechanisms of VGB-induced visual field loss.MethodsVGB was administered to mice via osmotic pump for two weeks to elevate GABA. VEP was examined, eye samples were collected and gene expression was measured by qRT-PCR. Similarly, human retinal pigment epithelial cells (ARPE19) were exposed to VGB and treated with mTOR inhibitors for mTOR pathway analysis, and to assess alterations in organelle accumulation by microscopy.ResultsDysregulated expression of transcripts in the mTOR pathway, GABAA/B receptors, metabotropic glutamate (Glu) receptors 1/6 and GABA/glutamate transporters in the eye was found in association with VEP changes during VGB administration. Rrag genes were found to be upregulated in both mouse eye and ARPE19 cells. Immunoblot of whole eye revealed >3-fold upregulation of a 200kDa band when immunoblotted for RRAGD. Microscopy of ARPE19 cells revealed selective reversal of VGB-induced organelle accumulation by autophagy inducing drugs, notably Torin 2 . Changes in mTOR pathway gene expression, including Rrag genes, were corrected by Torin 2 in ARPE19 cells.ConclusionsOur studies, indicating GABA-associated augmentation of RRAG/mTOR signaling, support further preclinical evaluation of mTOR inhibitors as a therapeutic strategy to potentially mitigate VGB-induced ocular toxicity.



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Child Neurology Recruitment and Training: views of residents and child neurologists from the 2015 AAP/CNS workforce survey

Publication date: Available online 3 October 2016
Source:Pediatric Neurology
Author(s): Donald L. Gilbert, Paul S. Horn, Peter B. Kang, Mark Mintz, Sucheta M. Joshi, Holly Ruch-Ross, James F. Bale
ObjectiveTo assess and compare resident and practicing child neurologists' attitudes regarding recruitment and residency training in child neurology.MethodsA joint taskforce of the American Academy of Pediatrics (AAP) and the Child Neurology Society (CNS) conducted an electronic survey of child neurology residents (n=305), practicing child neurologists (n=1290), and neurodevelopmental disabilities specialists (n=30) in 2015. Descriptive and multivariate analyses were performed.ResultsResponse rates were 32% for residents (n=97; 36% male; 65% Caucasian) and 40% for practitioners (n=523; 63% male; 80% Caucasian; 30% lifetime certification). Regarding recruitment, 70% (n=372) attributed difficulties recruiting medical students to insufficient early exposure. Although 68% (n=364) reported that their medical school required a neurology clerkship, just 28% (n=152) reported a child neurology component. Regarding residency curriculum, respondents supported increased training emphasis for genetics, neurodevelopmental disabilities, and multiple other subspecialty areas. Major changes in board certification requirements were supported, with 73% (n=363) favoring reduced adult neurology training (strongest predictors: fewer years since medical school p = 0.003; and, among practicing child neurologists, working more half day clinics per week p = 0.005). Further, 58% (n=289), favored an option to reduce total training to four years, with one year of general pediatrics. 82% (n=448) would definitely or probably choose child neurology again.ConclusionsThese findings provide support for recruitment efforts emphasizing early exposure of medical students to child neurology. Increased subspecialty exposure and an option for major changes in board certification requirements are favored by significant numbers of respondents.



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Significance of BDNF Val66Met Polymorphism in Brain Plasticity of Children

Publication date: Available online 3 October 2016
Source:Pediatric Neurology
Author(s): Kenneth A. Myers, Haley A. Vecchiarelli, Omar Damji, Matthew N. Hill, Adam Kirton




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Analysis of the prion protein gene in multiple system atrophy

Publication date: Available online 3 October 2016
Source:Neurobiology of Aging
Author(s): Viorica Chelban, Andreea Manole, Lasse Pihlstrøm, Lucia Schottlaender, Stephanie Efthymiou, Emer OConnor, Wassilios Meissner, Janice L. Holton, Henry Houlden
Neurodegenerative diseases are a very diverse group of disorders but they share some common mechanisms such as abnormally misfolded proteins with prion-like propagation and aggregation. Creutzfeldt - Jakob disease (CJD) is the most prevalent prion disease in humans. In the sporadic form of CJD the only known risk factor is the codon 129 polymorphism. Recent reports suggested that α-synuclein in MSA has similar pathogenic mechanisms as the prion protein (PrP). Here we present one Italian family with MSA and prion disease. Also, cases of concurrent MSA and prion pathology in the same individual or family suggest the possibility of molecular interaction between PrP and α-synuclein in the process of protein accumulation and neurodegeneration, warranting further investigations.We assessed the PRNP gene by whole exome sequencing in 264 pathologically confirmed MSA cases and 462 healthy controls to determine whether the two diseases share similar risk factors. We then analyzed codon 129 polymorphism by Sanger sequencing and compared with previously published results in sCJD. Homozygosity at codon 129 was present in 50% of pathologically confirmed MSA cases and in 58% of normal controls (OR 0.7 (95% CI of 0.5-0.9) compared with 88.2% in sCJD. Our data shows that the homozygous state of position 129 in the PRNP is not a risk factor for MSA. No other variants in the PRNP gene were associated with increased risk for MSA.



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Lack of Association of Mortalin (HSPA9) and Other Mitochondria-Related Genes with Risk of Parkinson’s and Alzheimer’s Diseases

Publication date: Available online 3 October 2016
Source:Neurobiology of Aging
Author(s): Sun Ju Chung, Mi-Jung Kim, Ho-Sung Ryu, Juyeon Kim, Young Jin Kim, Kiju Kim, Sooyeoun You, Seong Yoon Kim, Jae-Hong Lee
We investigated the role of mortalin (HSPA9) and its interaction with other mitochondria-related genes (parkin, PINK1, DJ1, and COQ2) as a risk factor for Parkinson's disease (PD) and Alzheimer's disease (AD) in 500 PD, 400 AD, and 500 control subjects. The HSPA9 variants identified by direct sequencing or its interaction with other genes assessed by genetic risk scores did not show a significant association with PD or AD risk. Our findings did not provide a strong evidence for the role of HAPA9 and its interaction with other mitochondria-related genes as a genetic risk factor for PD or AD.



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Clinical, Imaging, Pathological, and Biochemical Characterization of a Novel Presenilin 1 Mutation (N135Y) Causing Alzheimer’s Disease

Publication date: Available online 3 October 2016
Source:Neurobiology of Aging
Author(s): Marissa Natelson Love, David G. Clark, J. Nicholas Cochran, Kyle A. Den Beste, David S. Geldmacher, Tammie L. Benzinger, Brian A. Gordon, John C. Morris, Randall J. Bateman, Erik D. Roberson
We present two cases of early-onset Alzheimer's disease due to a novel N135Y mutation in PSEN1. The proband presented with memory and other cognitive symptoms at age 32. Detailed clinical characterization revealed initial deficits in memory with associated dysarthria, progressing to involve executive dysfunction, spastic gait, and episodic confusion with polyspike discharges on long-term electroencephalography. Amyloid- and FDG-PET scans showed typical results of Alzheimer's disease. By history, the proband's father had developed cognitive symptoms at age 42 and died at age 48. Neuropathological evaluation confirmed Alzheimer's disease, with moderate to severe amyloid angiopathy. Skeletal muscle showed type 2 fiber–predominant atrophy with pale central clearing. Genetic testing of the proband revealed an N135Y missense mutation in PSEN1. This mutation was predicted to be pathogenic by in silico analysis. Biochemical analysis confirmed that the mutation caused an increased Aβ42/Aβ40 ratio, consistent with other PSEN1 mutations and with a loss of presenilin function.



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Clinical features of Chinese patients with Gerstmann-Sträussler-Scheinker identified by targeted next-generation sequencing

Publication date: Available online 3 October 2016
Source:Neurobiology of Aging
Author(s): Hong-Fu Li, Zhi-Jun Liu, Hai-Lin Dong, Juan-Juan Xie, Shao-Yun Zhao, Wang Ni, Yi Dong, Zhi-Ying Wu
Gerstmann-Sträussler-Scheinker (GSS) is an autosomal dominant neurodegenerative disease due to mutations withinprion protein (PRNP) gene. Clinically, it is not easy to distinguish GSS from spinocerebellar ataxia (SCA), especially in the early stage of disease. We aimed to identify genetic mutations in 8 Chinese pedigrees with dominant ataxia but excluded dynamic mutations of SCA genes. Targeted next-generation sequencing was performed in the 8 probands. A customized panel was designed to capture 24 known causative genes, including 15 autosomal dominant SCA genes and 9 dementia-related genes. A two-year follow-up was performed in these patients who harbored mutation. Of the 8 probands, five were identified to harbor the p.P102L mutation within PRNP. All these five cases had progressive ataxia with age at onset ranging from 48 to 52 years (49.5 ± 4.51). Remarkable phenotypic heterogeneity was observed in them. Cognitive decline was found in 4/5 probands. The average duration from initial symptoms to cognitive decline is 32.5 months, ranging from 22 to 48months. In this study, we presented the detailed clinical features of five GSS pedigrees with PRNP p.P102L mutation. The variable phenotypes among these GSS patients indicated other genetic or environmental factors might be involved in the phenotypic heterogeneity of GSS. Our findings also support the proposal that screening of PRNP mutations should be performed for the patients with dominant ataxia if dynamic mutations of SCA genes were excluded.



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The miRNome of Alzheimer’s disease: consistent downregulation of the miR-132/212 cluster

Publication date: Available online 3 October 2016
Source:Neurobiology of Aging
Author(s): Sabrina Pichler, Wei Gu, Daniela Hartl, Gilles Gasparoni, Petra Leidinger, Andreas Keller, Eckart Meese, Manuel Mayhaus, Harald Hampel, Matthias Riemenschneider
MicroRNAs (miRNAs) are small non-coding RNA molecules, with essential functions in RNA silencing and post-transcriptional regulation of gene expression. MiRNAs appear to regulate the development and function of the nervous system. Alterations of miRNA expression have been associated with Alzheimer's disease (AD). To characterize the AD miRNA signature we examined genome wide miRNA and mRNA expression patterns in the temporal cortex of AD and control samples. We validated our miRNA results by semi-quantitative real-time PCR in independent prefrontal cortex. Further, we separated grey and white matter brain sections to identify the cellular origin of the altered miRNA expression. We observed genome wide downregulation of hsa-miR-132-3p and hsa-miR-212-3p in AD with a stronger decrease in grey matter AD samples. We further identified ten differently expressed transcripts achieving genome wide levels of significance. Significantly deregulated miRNAs and mRNAs were correlated and examined for potential binding sites (in silico). This miRNome-wide study in AD provides supportive evidence and corroborates an important contribution of miR-132/212 and corresponding target mRNAs to the pathogenesis of AD.



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Black:white disparities in breast cancer mortality in the 50 largest cities in the United States, 2005–2014

Publication date: Available online 3 October 2016
Source:Cancer Epidemiology
Author(s): Bijou R. Hunt, Marc S. Hurlbert
IntroductionThis paper presents race-specific breast cancer mortality rates and the corresponding rate ratios for the 50 largest U.S. cities for each of the 5-year intervals between 2005 and 2014.MethodsThe 50 largest cities in the U.S. were the units of analysis. Numerator data were abstracted from national death files where the cause was malignant neoplasm of the breast (ICD-10=C50) for women. Population-based denominators were obtained from the U.S. Census Bureau for 2010–2014. To measure the racial disparity, we calculated Black:White rate ratios (RRs) and confidence intervals for each 5-year period. To determine whether changes over time in the disparity were statistically significant, we calculated a 2-sided z score for the change in the relative percent difference between the Black and White rates for 2005–2009 and 2010–2014.ResultsAt the most recent time point (2010–2014), the RR was significantly greater than 1.00 in the US and 24 cities. The change in the Black:White disparity was statistically significant in five cities and the US. The percent difference increased significantly in Atlanta, GA (from 4.1 to 117.4, p<0.001); San Antonio, TX (from 24.4 to 79.3, p=0.034); and the US (from 39.7 to 43.1, p=0.007). The percent difference decreased significantly in Memphis, TN (from 111.0 to 68.9, p=0.043); Philadelphia, PA (from 43.1 to 23.5, p=0.049); and Boston, MA (from 48.9 to 0.7, p=0.022).ConclusionThis analysis provides updated city-level breast cancer mortality data for Black and White women through 2014, and reveals that in the US and 24 of the 43 largest US cities, Black women continue to die from breast cancer at a higher rate than their White counterparts. Importantly, however, a few cities, Memphis, Boston and Philadelphia, showed a decrease in the Black:White breast cancer mortality disparity between 2005–2009 and 2010–2014.



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Primary Cutaneous Adenosquamous Carcinoma of the Penis: The First Characterization of HPV Status in This Rare and Diagnostically Challenging Entity with Review of Glandular Carcinomas of the Penis

Abstract:

Glandular and pseudoglandular tumors of the penile skin are extremely uncommon and can present diagnostic challenges. Primary adenosquamous carcinoma of the penis is an extremely rare tumor, composed of distinct areas of malignant squamous and glandular cells, making it a diagnostically challenging entity. The World Health Organization (WHO) recognizes several subtypes of squamous cell carcinoma (SCC), each with its own distinctive pathologic appearance, clinical associations and prognosis. Among these variants is the exceedingly uncommon adenosquamous carcinoma (ASC), representing 1-2% of all SCC of the penis. Recent large studies have interrogated the presence of human papillomavirus (HPV) in malignant penile tumors and have shown specific morphologic patterns and clinical presentations to associate with HPV status. However, given the rarity of the adenosquamous variant of squamous cell carcinoma, it has largely been excluded from these studies. The glandular components of these lesions can present a confusing appearance, particularly when a large tumor is represented on a small biopsy. Here we describe a difficult histologic presentation of this rare tumor, with the first published characterization of the HPV status of this subtype. This case represents a distinctly unusual case of metastatic HPV-positive primary cutaneous adenosquamous carcinoma of the penis.

http://ift.tt/2dn31Ia

Ceritinib: a Review in ALK-Positive Advanced NSCLC

Abstract

Ceritinib (Zykadia™) is an oral, selective inhibitor of the anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase which, after genetic rearrangement, acts as an oncogenic driver in a proportion of non-small cell lung cancers (NSCLCs). The drug is approved in several countries worldwide for the treatment of patients with ALK-positive, advanced NSCLC who have previously received the first-generation ALK inhibitor crizotinib (indication details may vary by country). Approval was based on its clinical benefit in this setting in the phase I and II trials known as ASCEND-1 and −2. Across these noncomparative studies, 36–56 % of patients achieved a response with ceritinib (at the recommended dosage of 750 mg once daily) and the responses were durable, lasting up to a median of 10 months. Patients survived free from progression for a median of up to 7 months and had a median overall survival of up to 17 months. Moreover, efficacy outcomes in patients with brain metastases were generally consistent with those of the overall study populations. Ceritinib has an acceptable tolerability profile, with gastrointestinal issues, fatigue and liver test abnormalities being the most common adverse reactions. Thus, ceritinib is a valuable treatment option for patients with ALK-positive advanced NSCLC who have already received crizotinib therapy.

http://ift.tt/2dlxOZ1

Magnetic nanoparticle-induced hyperthermia with appropriate payloads: Paul Ehrlich’s “magic (nano)bullet” for cancer theranostics?

Publication date: Available online 3 October 2016
Source:Cancer Treatment Reviews
Author(s): N. R. Datta, S. Krishnan, D. E. Speiser, E. Neufeld, N. Kuster, S. Bodis, H. Hofmann
Effective multimodal cancer management requires the optimal integration of diagnostic and therapeutic modalities. Radiation therapy, chemotherapy and immunotherapy, alone or in combination, are integral parts of various cancer treatment protocols. Hyperthermia at 39-45°C is a potent radiosensitiser and has been shown to improve therapeutic outcomes in various tumours through its synergy with chemotherapy. Gene silencing approaches, using small interfering RNAs and microRNAs, are also being explored in clinical trials in oncology. The rapid developments in multifunctional nanoparticles provide ample opportunities to integrate both diagnostic and therapeutic modalities into a single effective cancer "theranostic" vector. Nanoparticles could extravasate passively into the tumour tissues in preference to the adjacent normal tissues by capitalizing on the enhanced permeability and retention effect. Tumour targeting might be further augmented by conjugating tumour-specific peptides and antibodies onto the surface of these nanoparticles or by activation through electromagnetic radiations, laser or ultrasound. Magnetic nanoparticles can induce hyperthermia in the presence of an alternating magnetic field, thereby multifunctionally with tumour-specific payloads empowering tumour specific radiotheranostics (for both imaging and radiotherapy), chemotherapy drug delivery, immunotherapy and gene silencing therapy. Such a (nano)bullet could realise the "magic bullet" conceived by Paul Ehrich more than a century ago. This article discusses the various aspects of this "magic (nano)bullet" and the challenges that need to be addressed to usher in this new paradigm in modern cancer diagnostics and therapeutics.



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Early Use of Chemotherapy in Metastatic Prostate Cancer

Publication date: Available online 3 October 2016
Source:Cancer Treatment Reviews
Author(s): Mark C. Markowski, Michael A. Carducci
Since 2010, five new antineoplastic therapies have been FDA approved for the treatment of metastatic prostate cancer. With additional treatment options, questions arose about the optimal sequence of these agents. Until recently, chemotherapy has been deferred until later in the disease course in favor of next-generation androgen deprivation therapy. Prior to the development of abiraterone acetate and enzalutamide, clinical trials were opened investigating the combination of chemotherapy with androgen deprivation therapy in patients with metastatic hormone-sensitive disease. With the development of new oral therapies used to treat castration-resistant disease, these trials were largely forgotten or felt to be obsolete. Recently, two trials have been reported showing an overall survival benefit of the early use of chemotherapy in patients with hormone-naive prostate cancer, changing the treatment paradigm for metastatic disease. Here we review the history of chemotherapy in treating prostate cancer and the emerging evidence favoring its use as first-line therapy against metastatic hormone-sensitive disease.



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