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Molecular therapy

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https://www.readbyqxmd.com/read/29332206/oncological-outcomes-after-cytoreductive-nephrectomy-for-patients-with-metastatic-renal-cell-carcinoma-with-inferior-vena-caval-tumor-thrombus
#1
Hideaki Miyake, Takayuki Sugiyama, Ryota Aki, Yuto Matsushita, Keita Tamura, Daisuke Motoyama, Toshiki Ito, Atsushi Otsuka
BACKGROUND: To evaluate the oncological outcomes of patients with metastatic renal cell carcinoma (mRCC) involving the inferior vena cava (IVC) who received cytoreductive nephrectomy. METHODS: This study included 75 consecutive metastatis renal cell carcinoma (mRCC) patients with inferior vena cava (IVC) tumor thrombus undergoing cytoreductive nephrectomy and tumor thrombectomy followed by systemic therapy. RESULTS: Of the 75 patients, 11, 33, 24 and 7 had level I, II, III and IV IVC thrombus, respectively...
January 13, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29331888/a-longitudinal-analysis-of-ido-and-pdl1-expression-during-immune-or-targeted-therapy-in-advanced-melanoma
#2
Lukas Krähenbühl, Simone M Goldinger, Joanna Mangana, Katrin Kerl, Ines Chevolet, Liève Brochez, Christine Horak, Mitch Levesque, Reinhard Dummer, Phil F Cheng
A deepened understanding of the cellular and molecular processes in the tumor microenvironment is necessary for the development of precision immunotherapy (IT). We simultaneously investigated CD3, PDL1, and IDO by immunohistochemistry in paired biopsies from various organs of 43 metastatic melanoma patients treated with IT and targeted therapy (TT). Intraindividual biopsies taken after a period of weeks to months demonstrate discordant results in 30% of the cases. Overlap of IDO and PDL1 increased after therapy...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29331789/anticonvulsant-activities-of-%C3%AE-asaronol-e-3-hydroxyasarone-an-active-constituent-derived-from-%C3%AE-asarone
#3
Xirui He, Yajun Bai, Min Zeng, Zefeng Zhao, Qiang Zhang, Ning Xu, Fanggang Qin, Xiaoyang Wei, Meimei Zhao, Ni Wu, Zehua Li, Yajun Zhang, Tai-Ping Fan, Xiaohui Zheng
BACKGROUND: Epilepsy is one of chronic neurological disorders that affects 0.5-1.0% of the world's population during their lifetime. There is a still significant need to develop novel anticonvulsant drugs that possess superior efficacy, broad spectrum of activities and good safety profile. METHODS: α-Asaronol and two current antiseizure drugs (α-asarone and carbamazepine (CBZ)) were assessed by in vivo anticonvulsant screening with the three most employed standard animal seizure models, including maximal electroshock seizure (MES), subcutaneous injection-pentylenetetrazole (PTZ)-induced seizures and 3-mercaptopropionic acid (3-MP)-induced seizures in mice...
August 31, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29331765/5-6-dihydropyrimidine-1-2h-carbothioamides-synthesis-in-vitro-gaba-at-screening-anticonvulsant-activity-and-molecular-modelling-study
#4
Meeta Sahu, Nadeem Siddiqui, Vidushi Sharma, Sharad Wakode
Even after considerable advances in the field of epilepsy treatment, convulsions are inefficiently controlled by standard drug therapy. Herein, a series of pyrimidine-carbothioamide derivatives 4(a-t) was designed as anticonvulsant agents by doing some important structural modifications in well-known anticonvulsant drugs. Two classical animal models were used for the in vivo anticonvulsant screening, maximum electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) models; followed by motor impairment study by rotarod method...
January 2, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29331759/astragaloside-iv-inhibits-cell-migration-and-viability-of-hepatocellular-carcinoma-cells-via-suppressing-long-noncoding-rna-atb
#5
Yaling Li, Yun Ye, Hongyan Chen
Astragaloside IV (AS-IV), the major active component of Astragalus membranaceus, has shown attractive anticancer effects in certain cancers. However, the roles and action mechanisms of AS-IV in hepatocellular carcinoma (HCC) are largely unclear. Long noncoding RNAs (lncRNAs) are recently revealed to have crucial roles in HCC initiation and progression, but whether lncRNAs participate in the anticancer roles of AS-IV are unknown. In this study, we demonstrated that AS-IV significantly downregulated lncRNA-ATB expression in a dose- and time-dependent manner in HCC cells...
January 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29331452/design-synthesis-and-evaluation-of-%C3%AE-turn-mimetics-as-lsd1-selective-inhibitors
#6
Yosuke Ota, Shin Miyamura, Misaho Araki, Yukihiro Itoh, Shusuke Yasuda, Mitsuharu Masuda, Tomoyuki Taniguchi, Yoshihiro Sowa, Toshiyuki Sakai, Kenichiro Itami, Junichiro Yamaguchi, Takayoshi Suzuki
Lysine-specific demethylase 1 (LSD1) is an attractive molecular target for cancer therapy. We have previously reported potent LSD1-selective inhibitors (i.e., NCD18, NCD38, and their analogs) consisting of trans-2-phenylcyclopropylamine (PCPA) or trans-2-arylcyclopropylamine (ACPA) and a lysine moiety that could form a γ-turn structure in the active site of LSD1. Herein we report the design, synthesis and evaluation of γ-turn mimetic compounds for further improvement of LSD1 inhibitory activity and anticancer activity...
January 2, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#7
Amritha Venkatesh, Harika Nandigam, Maria Muccioli, Manindra Singh, Tiffany Loftus, Deana Lewis, Michelle Pate, Fabian Benencia
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others...
November 22, 2017: Immunobiology
https://www.readbyqxmd.com/read/29331171/the-genotypic-and-phenotypic-spectrum-of-mto1-deficiency
#8
James J O'Byrne, Maja Tarailo-Graovac, Aisha Ghani, Michael Champion, Charu Deshpande, Ali Dursun, Riza K Ozgul, Peter Freisinger, Ian Garber, Tobias B Haack, Rita Horvath, Ivo Barić, Ralf A Husain, Leo A J Kluijtmans, Urania Kotzaeridou, Andrew A Morris, Colin J Ross, Saikat Santra, Jan Smeitink, Mark Tarnopolsky, Saskia B Wortmann, Johannes A Mayr, Michaela Brunner-Krainz, Holger Prokisch, Wyeth W Wasserman, Ron A Wevers, Udo F Engelke, Richard J Rodenburg, Teck Wah Ting, Robert McFarland, Robert W Taylor, Ramona Salvarinova, Clara D M van Karnebeek
BACKGROUND: Mitochondrial diseases, a group of multi-systemic disorders often characterized by tissue-specific phenotypes, are usually progressive and fatal disorders resulting from defects in oxidative phosphorylation. MTO1 (Mitochondrial tRNA Translation Optimization 1), an evolutionarily conserved protein expressed in high-energy demand tissues has been linked to human early-onset combined oxidative phosphorylation deficiency associated with hypertrophic cardiomyopathy, often referred to as combined oxidative phosphorylation deficiency-10 (COXPD10)...
January 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29331073/cerebrospinal-fluid-macrophage-biomarkers-in-amyotrophic-lateral-sclerosis
#9
A G Thompson, E Gray, M-L Thézénas, P D Charles, S Evetts, M T Hu, K Talbot, R Fischer, B M Kessler, M R Turner
Objective The neurodegenerative disease amyotrophic lateral sclerosis (ALS) is a heterogeneous clinical syndrome involving multiple molecular pathways. The development of biomarkers for use in therapeutic trials is a priority. We sought to use a high-throughput proteomic method to identify novel biomarkers in individual cerebrospinal fluid samples. Methods Liquid chromatography-tandem mass spectrometry with label-free quantification was used to identify cerebrospinal fluid proteins using samples from a well-characterised longitudinal cohort comprising patients with ALS (n=43), the upper motor neuron variant primary lateral sclerosis (PLS, n=6), cross-sectional healthy (n=20) and disease controls (Parkinsons's n=20, ALS mimic disorders n=12)...
January 13, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29331040/jun-gal-cd74-and-c1qb-as-potential-indicator-for-neuropathic-pain
#10
Ji-An Yang, Jun-Min He, Jing-Min Lu, Li-Juan Ji
Neuropathic pain is a kind of pain caused by primary or secondary impairment or dysfunction of peripheral or central nervous system. Patients with neuropathic pain were often with poor clinical outcome. We screened the differentially expressed genes between sciatic nerve injury and dorsal root ganglion gene in the sham operation model. Microarray and the spared nerve injury module were used to explore the molecular mechanism of neuropathic pain by injuries and the differentially expressed genes (DEGs) were identified out...
January 13, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29330548/shox-haploinsufficiency-presenting-with-isolated-short-long-bones-in-the-second-and-third-trimester
#11
Shwetha Ramachandrappa, Abhijit Kulkarni, Hina Gandhi, Cheryl Ellis, Renata Hutt, Lesley Roberts, Rosol Hamid, Aris Papageorghiou, Sahar Mansour
Haploinsufficiency of the transcription factor short stature homeobox (SHOX) manifests as a spectrum of clinical phenotypes, ranging from disproportionate short stature and Madelung deformity to isolated short stature. Here, we describe five infants with molecularly confirmed diagnoses of SHOX haploinsufficiency who presented in utero with short long bones during routine antenatal scanning from as early as 19 weeks gestation. Other foetal growth parameters were normal. The molecular basis of SHOX haploinsufficiency was distinct in each case...
January 12, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29330443/an-insight-into-intestinal-mucosal-microbiota-disruption-after-stroke
#12
Dragana Stanley, Robert J Moore, Connie H Y Wong
Recent work from our laboratory has provided evidence that indicates selective bacterial translocation from the host gut microbiota to peripheral tissues (i.e. lung) plays a key role in the development of post-stroke infections. Despite this, it is currently unknown whether mucosal bacteria that live on and interact closely with the host intestinal epithelium contribute in regulating bacterial translocation after stroke. Here, we found that the microbial communities within the mucosa of gastrointestinal tract (GIT) were significantly different between sham-operated and post-stroke mice at 24 h following surgery...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330406/adjuvant-role-of-septifast-to-improve-the-diagnosis-of-sepsis-in-a-large-cohort-of-hematological-patients
#13
Raffaella Greco, Maria Chiara Barbanti, Nicasio Mancini, Lara Crucitti, Chiara Oltolini, Alessandra Forcina, Francesca Lorentino, Luca Vago, Carlo Messina, Daniela Clerici, Mara Morelli, Fabio Giglio, Maria Teresa Lupo Stanghellini, Laura Infurnari, Matteo G Carrabba, Sarah Marktel, Andrea Assanelli, Paolo Scarpellini, Massimo Bernardi, Jacopo Peccatori, Consuelo Corti, Massimo Clementi, Fabio Ciceri
Febrile neutropenia and sepsis are common and life-threatening complications in hematological diseases. This study was performed retrospectively in 514 patients treated for febrile neutropenia at our institute, to investigate the clinical usefulness of a molecular tool, LightCycler® SeptiFast test (SF), to promptly recognize pathogens causing sepsis in hematological patients. We collected 1837 blood samples of 514 consecutive hematological patients. The time of processing is short. Overall, 757 microorganisms in 663 episodes were detected by molecular test and standard blood cultures (BC): 73...
January 12, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29330367/characterization-of-human-small-heat-shock-protein-hspb1-%C3%AE-crystallin-domain-localized-mutants-associated-with-hereditary-motor-neuron-diseases
#14
Stephen D Weeks, Lydia K Muranova, Michelle Heirbaut, Steven Beelen, Sergei V Strelkov, Nikolai B Gusev
Congenital mutations in human small heat shock protein HSPB1 (HSP27) have been linked to Charcot-Marie-Tooth disease, a commonly occurring peripheral neuropathy. Understanding the molecular mechanism of such mutations is indispensable towards developing future therapies for this currently incurable disorder. Here we describe the physico-chemical properties of the autosomal dominant HSPB1 mutants R127W, S135F and R136W. Despite having a nominal effect on thermal stability, the three mutations induce dramatic changes to quaternary structure...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330358/pathogenesis-of-bone-disease-in-multiple-myeloma-from-bench-to-bedside
#15
REVIEW
Evangelos Terpos, Ioannis Ntanasis-Stathopoulos, Maria Gavriatopoulou, Meletios A Dimopoulos
Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and mortality. The basis of the pathogenesis of myeloma-related bone disease is the uncoupling of the bone-remodeling process. The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and suppression of osteoblasts, resulting in bone loss. Several intracellular and intercellular signaling cascades, including RANK/RANKL/OPG, Notch, Wnt, and numerous chemokines and interleukins are implicated in this complex process...
January 12, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29330334/detection-of-heterozygous-mutation-in-hook-microtubule-tethering-protein-1-in-three-patients-with-decapitated-and-decaudated-spermatozoa-syndrome
#16
Huixing Chen, Yong Zhu, Zijue Zhu, Erlei Zhi, Keming Lu, Xiaobo Wang, Feng Liu, Zheng Li, Weiliang Xia
BACKGROUND: The mechanism of intramanchette transport is crucial to the transformation of sperm tail and the nuclear condensation during spermiogenesis. Although few dysfunctional proteins could result in abnormal junction between the head and tail of spermatozoon, little is known about the genetic cues in this process. OBJECTIVE: Based on patients with severe decapitated and decaudated spermatozoa (DDS) syndrome, the study aimed to validate whether new mutation exists on their Hook microtubule-tethering protein 1 (HOOK1) genes and follow their results of assisted reproduction treatment (ART)...
January 12, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29330298/stemness-is-enhanced-in-gastric-cancer-by-a-set-pp2a-e2f1-axis
#17
Shuhei Enjoji, Ryotaro Yabe, Shunya Tsuji, Kazuhiro Yoshimura, Hideyoshi Kawasaki, Masashi Sakurai, Yusuke Sakai, Hiroko Takenouchi, Shigefumi Yoshino, Shoichi Hazama, Hiroaki Nagano, Hiroko Oshima, Masanobu Oshima, Michael P Vitek, Tetsuya Matsuura, Yoshitaka Hippo, Tatsuya Usui, Takashi Ohama, Koichi Sato
Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Chemotherapies against gastric cancer often fail, with cancer recurrence due potentially to the persistence of cancer stem cells. This unique subpopulation of cells in tumors possess the ability to self-renew and de-differentiate. These cancer stem cells are critical for initiation, maintenance, metastasis, and relapse of cancers; however, the molecular mechanisms supporting cancer stemness remain largely unknown...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330209/cognitive-computing-to-guide-molecular-based-therapy-selection-steps-forward-amid-abundant-need
#18
Leif W Ellisen
No abstract text is available yet for this article.
January 12, 2018: Oncologist
https://www.readbyqxmd.com/read/29330205/clinical-utility-of-a-stat3-regulated-microrna-200-family-signature-with-prognostic-potential-in-early-gastric-cancer
#19
Liang Yu, Di Wu, Hugh Gao, Jesse Balic, Anna Tsykin, Tae-Su Han, You Dong Liu, Catherine Lydia Kennedy, Ji-Kun Li, Jie-Qi Mao, Patrick Tan, Masanobu Oshima, Gregory J Goodall, Brendan J Jenkins
PURPOSE: The majority of gastric cancer (GC) patients are diagnosed with late stage disease, for which distinct molecular subtypes have been identified that are potentially amenable to targeted therapies. However, there exists no molecular classification system with prognostic power for early stage GC (EGC) because the molecular events promoting GC initiation remain ill-defined. EXPERIMENTAL DESIGN: miRNA microarrays were performed on gastric tissue from the gp130F/F preclinical EGC mouse model, prior to tumor initiation...
January 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29329981/molecular-cloning-and-characterization-of-leucine-aminopeptidase-gene-from-taenia-pisiformis
#20
Shaohua Zhang, Xuepeng Cai, Xuenong Luo, Shuai Wang, Aijiang Guo, Junling Hou, Run Wu
Leucine aminopeptidase (LAP, EC: 3.4.11.1) is an important metalloexopeptidase that catalyze the hydrolysis of amino-terminal leucine residues from polypeptides and proteins. In this study, a full length of cDNA encoding leucine aminopeptidase of Taenia pisiformis (TpLAP) was cloned by rapid amplification of cDNA-ends using the polymerase chain reaction (RACE-PCR) method. The full-length cDNA of the TpLAP gene is 1823 bp and contains a 1569 bp ORF encoding 533 amino acids with a putative mass of 56.4 kDa...
January 9, 2018: Experimental Parasitology
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