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Arunava Ghosh, Suresh Babu Rangasamy, Khushbu K Modi, Kalipada Pahan
Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) is a rare neurodegenerative disease caused by mutations in the Cln2 gene that leads to deficiency or loss of function of the tripeptidyl peptidase 1 (TPP1) enzyme. TPP1 deficiency is known to cause the accumulation of autofluoroscent lipid-protein pigments in brain. Similar to other neurodegenerative disorders, LINCL is also associated with neuroinflammation and neuronal damage. Despite investigations, no effective therapy is currently available for LINCL...
February 15, 2017: Journal of Neurochemistry
Kentaro Igarashi, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Arun S Singh, Scott D Nelson, Sarah Dry, Yunfeng Li, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Undifferentiated spindle-cell sarcoma (USCS) is a recalcitrant cancer. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). In the present study, we evaluated the efficacy of standard first-line chemistry of doxorubicin (DOX), gemcitabine (GEM) combined with docetaxel (DOC), compared to pazopanib (PAZ), a multi-targeting tyrosine-kinase inhibitor, in an USCS PDOX model. A high-grade USCS from a striated muscle of the patients was grown orthotopically in the right biceps femoris muscle of nude mice to establish the PDOX model...
February 8, 2017: Journal of Cellular Biochemistry
Yongkook Kim, Hiromitsu Hoshino, Naruyasu Kakita, Masaru Yamasaki, Yohei Hosoda, Masaya Nishino, Miho Okano, Junji Kawada, Masaki Okuyama, Toshimasa Tsujinaka
A 70-year-old woman with locally advanced pancreatic body cancer invading the celiac axis underwent 4 courses of preoperative chemotherapy consisting of gemcitabine(GEM)plus nab-paclitaxel(nab-PTX)on days 1, 8, and 15 every 4 weeks, followed by radiation therapy(CRT; 50.4Gy delivered in 28 daily fractions). The tumor size was greatly diminished and levels of all tumor markers were decreased. R0resection by distal pancreatectomy with en bloc celiac axis resection(DP-CAR)was performed. The histopathologic findings showed that the effect of CRT was grade 2b(Evans' classification), and the surgical margins were histologically clear...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Yutaka Takeda, Yoshiteru Katsura, Yoshiaki Ohmura, Takuya Sakamoto, Yasuki Akiyama, Ryuichi Kuwahara, Yoshihiro Morimoto, Tomo Ishida, Yasuo Oneda, Kouhei Murakami, Atsushi Naito, Yoshinori Kagawa, Atsushi Takeno, Takeshi Kato, Shigeyuki Tamura
BACKGROUND: Pancreatic adenocarcinoma is one of the leading causes of cancer deaths in Japan.Albumin -bound paclitaxel (nab-paclitaxel)plus gemcitabine hydrochloride(GEM)combination chemotherapy provided significant improvements in the overall and progression-free survival in a phase III trial in Europe and America and a phase II trial in Japan.As a result, this combination therapy was approved for use in Japan. METHODS: We evaluated the efficacy of nab-paclitaxel plus GEM with metastatic or recurrent pancreatic cancer...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Milena A Gianfrancesco, M Maria Glymour, Stefan Walter, Brooke Rhead, Xiaorong Shao, Ling Shen, Hong Quach, Alan Hubbard, Ingileif Jónsdóttir, Kári Stefánsson, Pernilla Strid, Jan Hillert, Anna Hedström, Tomas Olsson, Ingrid Kockum, Catherine Schaefer, Lars Alfredsson, Lisa F Barcellos
Multiple sclerosis (MS) is an autoimmune disease with both genetic and environmental risk factors. Recent studies indicate that childhood and adolescent obesity double the risk of MS, but this association may reflect unmeasured confounders rather than causal effects of obesity. We used separate-sample Mendelian randomization to estimate the causal effect of body mass index (BMI) on susceptibility to MS. Using data from non-Hispanic white members of the Kaiser Permanente Medical Care Plan of Northern California (KPNC) (2006-2014; 1,104 cases of MS and 10,536 controls) and a replication data set from Sweden (the Epidemiological Investigation of MS (EIMS) and the Genes and Environment in MS (GEMS) studies, 2005-2013; 5,133 MS cases and 4,718 controls), we constructed a weighted genetic risk score using 97 variants previously established to predict BMI...
January 9, 2017: American Journal of Epidemiology
Zhenyu Duan, Yanhong Zhang, Hongyan Zhu, Ling Sun, Hao Cai, Bijin Li, Qiyong Gong, Zhongwei Gu, Kui Luo
The availability and the stability of current anticancer agents, particularly water-insoluble drugs, are still far from satisfactory. A widely used anticancer drug, gemcitabine (GEM), is so poorly stable in circulation that some polymeric drug-delivery systems have been under development for some time to improve its therapeutic index. Herein, we designed, prepared, and characterized a biodegradable amphiphilic block N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-GEM conjugate-based nanoscale and stimuli-sensitive drug-delivery vehicle...
February 1, 2017: ACS Applied Materials & Interfaces
Manish Bodas, Neel Patel, David Silverberg, Kyla Walworth, Neeraj Vij
AIMS: Recent studies have shown that cigarette smoke (CS)-induced oxidative stress impairs autophagy, resulting in aggresome-formation that correlates with severity of chronic obstructive pulmonary disease (COPD)-emphysema, although the specific step in autophagy pathway that is impaired is unknown. Hence, in this study, we aimed to evaluate the role of master autophagy transcription factor EB (TFEB) in CS-induced COPD-emphysema pathogenesis. RESULTS: We first observed that TFEB accumulates in perinuclear spaces as aggresome-bodies in COPD lung tissues of tobacco smokers and severe emphysema subjects, compared with non-emphysema or nonsmoker controls...
February 1, 2017: Antioxidants & Redox Signaling
Olubode A Olufajo, Gally Reznor, Stuart R Lipsitz, Zara R Cooper, Adil H Haider, Ali Salim, Erika L Rangel
BACKGROUND: The risk of mortality after emergency general surgery (EGS) in elderly patients is prolonged beyond initial hospitalization. Our objective was to develop a preoperative scoring tool to quantify risk of 1-year mortality. METHODS: Three hundred ninety EGS patients aged 70 years or more were analyzed. Risk factors for 1-year mortality were identified using stepwise-forward logistic multivariate regression and weights assigned using natural logarithm of odds ratios...
September 3, 2016: American Journal of Surgery
Joby John, Jonathan B Dingwell, Joseph P Cusumano
We study inter-trial movement fluctuations exhibited by human participants during the repeated execution of a virtual shuffleboard task. Focusing on skilled performance, theoretical analysis of a previously-developed general model of inter-trial error correction is used to predict the temporal and geometric structure of variability near a goal equivalent manifold (GEM). The theory also predicts that the goal-level error scales linearly with intrinsic body-level noise via the total body-goal sensitivity, a new derived quantity that illustrates how task performance arises from the interaction of active error correction and passive sensitivity properties along the GEM...
September 2016: PLoS Computational Biology
Riley Bove, Alicia S Chua, Zongqi Xia, Lori Chibnik, Philip L De Jager, Tanuja Chitnis
OBJECTIVE: To examine the relationship between 2 markers of early multiple sclerosis (MS) onset, 1 genetic (HLA-DRB1*1501) and 1 experiential (early menarche), in 2 cohorts. METHODS: We included 540 white women with MS or clinically isolated syndrome (N = 156 with genetic data available) and 1,390 white women without MS but with a first-degree relative with MS (Genes and Environment in Multiple Sclerosis [GEMS]). Age at menarche, HLA-DRB1*1501 status, and age at MS onset were analyzed...
August 2016: Neurology. Genetics
Yu-Ting Tseng, Cheng-Sheng Chen, Yuh-Jyh Jong, Fang-Rong Chang, Yi-Ching Lo
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by motor neurons degeneration and muscular atrophy. There is no effective SMA treatment. Loganin is a botanical candidate with anti-inflammatory, anti-oxidant, glucose-lowering and anti-diabetic nephropathy activities. The aim of this study is to investigate the potential protective effects of loganin on SMA using two cellular models, SMN-deficient NSC34 cells and SMA patient fibroblasts, and an animal disease model, SMAΔ7 mice...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
I G Gonzalez-Martinez, A Bachmatiuk, V Bezugly, J Kunstmann, T Gemming, Z Liu, G Cuniberti, M H Rümmeli
As the success of nanostructures grows in modern society so does the importance of our ability to control their synthesis in precise manners, often with atomic precision as this can directly affect the final properties of the nanostructures. Hence it is crucial to have both deep insight, ideally with real-time temporal resolution, and precise control during the fabrication of nanomaterials. Transmission electron microscopy offers these attributes potentially providing atomic resolution with near real time temporal resolution...
June 2, 2016: Nanoscale
Na-Kyung Han, Dae Hwan Shin, Jung Seok Kim, Kwon Yeon Weon, Chang-Young Jang, Jin-Seok Kim
Investigation of potential therapeutics for targeting breast cancer stem cells (BCSCs) is important because these cells are regarded as culprit of breast cancer relapse. Accomplishing this kind of strategy requires a specific drug-delivery system using the distinct features of liposomes. Studies on targeted liposomal delivery systems have indicated the conjugation of hyaluronan (HA), a primary ligand for CD44 surface markers, as an appropriate method for targeting BCSCs. For this study, enriched BCSCs were obtained by culturing MCF-7 breast cancer cells in nonadherent conditions...
2016: International Journal of Nanomedicine
Celeste K Wong, Pamela L Horn-Ross, Gilbert C Gee, Salma Shariff-Marco, Thu Quach, Laura Allen, Roxanna Bautista, Patricia Quema La Chica, Winston Tseng, Pancho Chang, Christina A Clarke, Juan Yang, Gem M Le, Alison Canchola, Melinda L Irwin, Sandra Soo-Jin Lee, Scarlett Lin Gomez
BACKGROUND: Data are limited on effective methods for recruiting persons, especially from ethnically diverse populations, into population-based studies. The goal of this study was to evaluate the variation among and representativeness of controls identified using multiple methods for a population-based case-control study of breast cancer among Asian Americans, Native Hawaiians and Pacific Islanders (AANHPIs) in the San Francisco Bay Area. METHODS: We used a unique combination of targeted recruitment strategies, including address-based sampling, community-based methods, and internet-based and media-based approaches for recruiting controls, frequency matched on age and ethnicity to a population-based sample of cases...
October 2016: Journal of Epidemiology and Community Health
Myriam Scherer, Thomas Stamminger
Research in the last 2 decades has demonstrated that a specific organelle of the cell nucleus, termed PML nuclear body (PML-NB) or nuclear domain 10 (ND10), is frequently modified during viral infection. This correlates with antagonization of a direct repressive function of individual PML-NB components, such as the PML, hDaxx, Sp100, or ATRX protein, that are able to act as cellular restriction factors. Recent studies now reveal an emerging role of PML-NBs as coregulatory structures of both type I and type II interferon responses...
July 1, 2016: Journal of Virology
Henry W C Leung, Agnes L F Chan, Chih-Hsin Muo
PURPOSE: The purpose of this study was to evaluate the cost-effectiveness of gemcitabine plus modern radiotherapy versus gemcitabine alone in the treatment of locally advanced pancreatic cancer in Taiwan. METHODS: A Markov decision-analytic model was performed to compare the cost-effectiveness of 3 treatment regimens; gemcitabine alone (gem-alone), gemcitabine plus intensity-modulated radiotherapy (gem-IMRT), and gemcitabine plus stereotactic body radiotherapy (gem-SBRT)...
2016: Clinical Therapeutics
Ke-Jun Han, Daniel Foster, Edward W Harhaj, Monika Dzieciatkowska, Kirk Hansen, Chang-Wei Liu
Low levels of the survival motor neuron (SMN) protein cause spinal muscular atrophy, the leading genetic disorder for infant mortality. SMN is ubiquitously expressed in various cell types and localizes in both the cytoplasm and the nucleus, where it concentrates in two subnuclear structures termed Cajal body (CB) and gems. In addition, SMN can also be detected in the nucleolus of neurons. Mechanisms that control SMN sorting in the cell remain largely unknown. Here, we report that the ubiquitin (Ub) ligase Itch directly interacts with and monoubiquitinates SMN...
April 1, 2016: Human Molecular Genetics
Keisuke Otani, Teruki Teshima, Yuri Ito, Yoshifumi Kawaguchi, Koji Konishi, Hidenori Takahashi, Hiroaki Ohigashi, Kazuya Oshima, Nobuhito Araki, Kinji Nishiyama, Osamu Ishikawa
BACKGROUND AND PURPOSE: Preoperative chemoradiotherapy (CRT) with gemcitabine (GEM) for pancreatic cancer is often accompanied by vertebral compression fractures (VCFs). This study aimed to establish the incidence of VCFs and identify the related risk factors (RFs) to elucidate how to decrease the overall incidence of VCF. MATERIAL AND METHODS: We investigated 220 patients with resectable or borderline-resectable pancreatic cancers who had completed preoperative CRT between 2006 and 2011...
March 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Yoshiteru Katsura, Yutaka Takeda, Yoshiaki Ohmura, Yurina Motoyama, Tomo Ishida, Yoshihiro Morimoto, Katsunori Matsushita, Atsushi Naito, Kohei Murakami, Yoshinori Kagawa, Masatsugu Okishiro, Atsushi Takeno, Chiyomi Egawa, Takeshi Kato, Shigeyuki Tamura
Pancreatic ductal carcinoma is a highly aggressive cancer, with one of the highest mortality rates among gastrointestinal cancers. Nab-paclitaxel plus gemcitabine (GEM) significantly improved overall survival, progression-free survival, and response rate in a phase Ⅲ trial in 151 community and academic centers in 11 countries. As a result, nab-paclitaxel plus GEM was approved for use in December 2014 in Japan. We report a case of a patient with pancreatic cancer who underwent this chemotherapy. A 47-year-old man was admitted to our hospital for evaluation of pancreatic lesions...
November 2015: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Mami Muramatsu, Aya Tsuchiya, Seiko Ohta, Yukie Iijima, Miyuki Maruyama, Yoshiko Onodera, Megumi Hagihara, Naoki Nakaya, Itaru Sato, Kenji Omura, Soichiro Ueno, Hideo Nakajima
In order to examine the effect on body composition of anticancer drug treatments, the body composition rate in patients being treated with gemcitabine (GEM)-based chemotherapy was measured over time on an outpatient basis with a simple body composition monitor using the bioelectrical impedance (BI) method. The results revealed a significant reduction in the body fat rate (P=0.01) over the course of treatment in patients with pancreatobiliary tract cancer who became unable to continue GEM-based chemotherapy due to progressive disease or a decreased performance status...
December 2015: Oncology Letters
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