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Clinical pathway

Mijung Kwon, Jae-Hoon Kim, Yevangelina Rybak, Alex Luna, Chel Hun Choi, Joon-Yong Chung, Stephen M Hewitt, Asha Adem, Elizabeth Tubridy, Juan Lin, Steven K Libutti
Filamin A interacting protein 1-like (FILIP1L) is an inhibitor of the canonical WNT pathway. WNT/β-catenin signaling and its downstream pathway, epithelial-to-mesenchymal transition (EMT), play a key role in ovarian cancer metastasis and chemoresistance. To study the clinical implications of FILIP1L in regulating the WNT/β-catenin pathway, the expression of FILIP1L, β-catenin, SNAIL and SLUG was analyzed by immunohistochemistry on tissue microarrays of 369 ovarian samples ranging from normal to metastatic...
October 20, 2016: Oncotarget
Pavel Sumazin, Yidong Chen, Lisa R Treviño, Stephen F Sarabia, Oliver A Hampton, Kayuri Patel, Toni-Ann Mistretta, Barry Zorman, Patrick Thompson, Andras Heczey, Sarah Comerford, David A Wheeler, Murali Chintagumpala, Rebecka Meyers, Dinesh Rakheja, Milton J Finegold, Gail Tomlinson, D Williams Parsons, Dolores López-Terrada
Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pre-treatment tumors have been molecularly profiled and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pre-treatment HBs at diagnosis. Our analysis of 88 clinically-annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated NFE2L2 activity, high LIN28B, HMGA2, SALL4 and AFP expression, and high coordinated expression of oncofetal proteins and stem cell markers; while low-risk tumors had low LIN28B and let-7 expression, and high HNF1A activity...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Ursula N Broder, Tina Jaeger, Urs Jenal
Virulence of pathogenic bacteria is a tightly controlled process to facilitate invasion and survival in host tissues. Although pathways controlling virulence have been defined in detail, signals modulating these processes are poorly understood. The opportunistic pathogen Pseudomonas aeruginosa causes acute and chronic infections in humans. Disease progression is typically associated with a loss of acute virulence and the emergence of biofilms and chronic behaviour. The acute-to-chronic switch is governed by the global Gac/Rsm pathway...
October 24, 2016: Nature Microbiology
Philip Egan, Stephen Drain, Caroline Conway, Anthony J Bjourson, H Denis Alexander
Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient's age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies...
October 21, 2016: International Journal of Molecular Sciences
Hongtao Guo, Xuyan Niu, Yan Gu, Cheng Lu, Cheng Xiao, Kevin Yue, Ge Zhang, Xiaohua Pan, Miao Jiang, Yong Tan, Hongwei Kong, Zhenli Liu, Guowang Xu, Aiping Lu
Pattern classification is a key approach in Traditional Chinese Medicine (TCM), and it is used to classify the patients for intervention selection accordingly. TCM cold and heat patterns, two main patterns of rheumatoid arthritis (RA) had been explored with systems biology approaches. Different regulations of apoptosis were found to be involved in cold and heat classification in our previous works. For this study, the metabolic profiling of plasma was explored in RA patients with typical TCM cold or heat patterns by integrating liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) platforms in conjunction with the Ingenuity Pathway Analysis (IPA) software...
October 21, 2016: International Journal of Molecular Sciences
Kaiyu Qian, Gang Wang, Rui Cao, Tao Liu, Guofeng Qian, Xinyuan Guan, Zhongqiang Guo, Yu Xiao, Xinghuan Wang
Capsaicin (CAP), a highly selective agonist for transient receptor potential vanilloid type 1 (TRPV1), has been widely reported to exhibit anti-oxidant, anti-inflammation and anticancer activities. Currently, several therapeutic approaches for bladder cancer (BCa) are available, but accompanied by unfavorable outcomes. Previous studies reported a potential clinical effect of CAP to prevent BCa tumorigenesis. However, its underlying molecular mechanism still remains unknown. Our transcriptome analysis suggested a close link among calcium signaling pathway, cell cycle regulation, ROS metabolism and FOXO signaling pathway in BCa...
October 21, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Marta Spodenkiewicz, Carmen Diez-Fernandez, Véronique Rüfenacht, Corinne Gemperle-Britschgi, Johannes Häberle
Glutamine synthetase (GS) is a cytosolic enzyme that produces glutamine, the most abundant free amino acid in the human body. Glutamine is a major substrate for various metabolic pathways, and is thus an important factor for the functioning of many organs; therefore, deficiency of glutamine due to a defect in GS is incompatible with normal life. Mutations in the human GLUL gene (encoding for GS) can cause an ultra-rare recessive inborn error of metabolism-congenital glutamine synthetase deficiency. This disease was reported until now in only three unrelated patients, all of whom suffered from neonatal onset severe epileptic encephalopathy...
October 19, 2016: Biology
Guillaume Passot, Delphine Vaudoyer, Laurent Villeneuve, Florent Wallet, Annie-Claude Beaujard, Gilles Boschetti, Pascal Rousset, Naoual Bakrin, Eddy Cotte, Olivier Glehen
OBJECTIVE: To determine whether a perioperative, standardized clinical pathway could impact the failure-to-rescue rate after cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) in a tertiary center. SUMMARY OF BACKGROUND DATA: Morbidity and mortality remain significant after CRS for PC. Clinical pathways have been associated with better outcomes after surgery. The failure-to-rescue rate is a useful metric for evaluating quality in surgery. MATERIALS AND METHODS: This study included 666 patients that received CRS for PC between 2009 and 2014...
April 11, 2016: Annals of Surgery
Akshay Shekhar, Xianming Lin, Fang-Yu Liu, Jie Zhang, Huan Mo, Lisa Bastarache, Joshua C Denny, Nancy J Cox, Mario Delmar, Dan M Roden, Glenn I Fishman, David S Park
Rapid impulse propagation in the heart is a defining property of pectinated atrial myocardium (PAM) and the ventricular conduction system (VCS) and is essential for maintaining normal cardiac rhythm and optimal cardiac output. Conduction defects in these tissues produce a disproportionate burden of arrhythmic disease and are major predictors of mortality in heart failure patients. Despite the clinical importance, little is known about the gene regulatory network that dictates the fast conduction phenotype. Here, we have used signal transduction and transcriptional profiling screens to identify a genetic pathway that converges on the NRG1-responsive transcription factor ETV1 as a critical regulator of fast conduction physiology for PAM and VCS cardiomyocytes...
October 24, 2016: Journal of Clinical Investigation
Hanna Starobinets, Jordan Ye, Miranda Broz, Kevin Barry, Juliet Goldsmith, Timothy Marsh, Fanya Rostker, Matthew Krummel, Jayanta Debnath
The rising success of cancer immunotherapy has produced immense interest in defining the clinical contexts that may benefit from this therapeutic approach. To this end, there is a need to ascertain how the therapeutic modulation of intrinsic cancer cell programs influences the anticancer immune response. For example, the role of autophagy as a tumor cell survival and metabolic fitness pathway is being therapeutically targeted in ongoing clinical trials that combine cancer therapies with antimalarial drugs for the treatment of a broad spectrum of cancers, many of which will likely benefit from immunotherapy...
October 24, 2016: Journal of Clinical Investigation
Andrew J Massey
Clinical development of Chk1 inhibitors is currently focussed on evaluating activity as monotherapy and as potentiators of chemotherapy. To aid translation of pre-clinical studies, we sought to understand the effects of the tumour growth environment on Chk1 signalling and sensitivity to small molecule Chk1 inhibition. Spheroid culture altered Chk1 signalling to a more xenograft like state but decreased sensitivity to Chk1 inhibition. Growth in low serum did not alter DDR signalling but increased the sensitivity of A2058 and U2OS tumour cells to Chk1 inhibition...
October 24, 2016: Scientific Reports
N Garg, D Bakhshinyan, C Venugopal, S Mahendram, D A Rosa, T Vijayakumar, B Manoranjan, R Hallett, N McFarlane, K H Delaney, J M Kwiecien, C C Arpin, P-S Lai, R F Gómez-Biagi, A M Ali, E D de Araujo, O A Ajani, J A Hassell, P T Gunning, S K Singh
Medulloblastoma (MB), the most common malignant paediatric brain tumor, is currently treated using a combination of surgery, craniospinal radiotherapy and chemotherapy. Owing to MB stem cells (MBSCs), a subset of MB patients remains untreatable despite standard therapy. CD133 is used to identify MBSCs although its functional role in tumorigenesis has yet to be determined. In this work, we showed enrichment of CD133 in Group 3 MB is associated with increased rate of metastasis and poor clinical outcome. The signal transducers and activators of transcription-3 (STAT3) pathway are selectively activated in CD133(+) MBSCs and promote tumorigenesis through regulation of c-MYC, a key genetic driver of Group 3 MB...
October 24, 2016: Oncogene
Zsófia Bérces, Kinga Tóth, Gergely Márton, Ildikó Pál, Bálint Kováts-Megyesi, Zoltán Fekete, István Ulbert, Anita Pongrácz
Neural interface technologies including recording and stimulation electrodes are currently in the early phase of clinical trials aiming to help patients with spinal cord injuries, degenerative disorders, strokes interrupting descending motor pathways, or limb amputations. Their lifetime is of key importance; however, it is limited by the foreign body response of the tissue causing the loss of neurons and a reactive astrogliosis around the implant surface. Improving the biocompatibility of implant surfaces, especially promoting neuronal attachment and regeneration is therefore essential...
October 24, 2016: Scientific Reports
Ma Ke, Xi Chen, Jia-Cheng Chen, Ying Wang, Xi-Meng Zhang, Fan Huang, Jun-Jiong Zheng, Xiong Chen, Wei Yu, Ke-Ling Cheng, Yan-Qing Feng, Huai-Yu Gu
Rifampicin, a broad-spectrum antibiotic, has neuroprotective, immunosuppressive, and anti-inflammatory properties. However, the effect of rifampicin on autoimmune disorders of the nervous system is not clear. In this study, we investigated whether rifampicin was beneficial for myelin oligodendrocyte glycoprotein peptide (MOG33-35 )-induced female C57BL/6 experimental autoimmune encephalomyelitis (EAE) mice, the well-established animal model of multiple sclerosis (MS). Rifampicin treatment (daily from the first day after EAE immunization) remarkably attenuated clinical signs and loss of body weight, which are associated with suppression of inflammatory infiltration and demyelination in spinal cords of EAE mice...
October 23, 2016: Journal of Neurochemistry
Soo Young Kim, Min Seok Hur, Byung Gon Choi, Min Jung Kim, Yang Won Lee, Yong Beom Choe, Kyu Joong Ahn
Psoriasis is a polygenic and multifactorial disease showing ethnic differences in terms of its severity and frequency. Therapies targeting interleukin 17A (IL-17A), interleukin 17 receptor (IL-17R), and Janus kinases (JAKs) are in clinical development for the treatment of psoriasis, and their success suggests the essential role of these molecules in psoriasis. To investigate the genetic susceptibility in T helper 17 (Th17) cell signal transduction pathways for promoting psoriasis, we performed candidate gene and linkage disequilibrium analysis...
October 24, 2016: Clinical and Experimental Immunology
Alberto Cacciola, Demetrio Milardi, Alessandro Calamuneri, Lilla Bonanno, Silvia Marino, Pietro Ciolli, Margherita Russo, Daniele Bruschetta, Antonio Duca, Fabio Trimarchi, Angelo Quartarone, Giuseppe Anastasi
According to the classical view, the cerebellum has long been confined to motor control physiology; however, it has now become evident that it exerts several non-somatic features other than the coordination of movement and is engaged also in the regulation of cognition and emotion. In a previous diffusion-weighted imaging-constrained spherical deconvolution (CSD) tractography study, we demonstrated the existence of a direct cerebellum-hippocampal pathway, thus reinforcing the hypothesis of the cerebellar role in non-motor domains...
October 24, 2016: Cerebellum
Rifang Liao, Fengxia Yan, Zhuanping Zeng, Mohd Farhan, Peter Little, Remi Quirion, Lalit K Srivastava, Wenhua Zheng
Amiodarone (AM) is the most effective antiarrhythmic agent currently available. However, clinical application of AM is limited by its serious toxic adverse effects including optic neuropathy. The purpose of this study was to explore the effects of AM and to assess if insulin-like growth factor-1 (IGF-1) could protect retinal neuronal cells from AM-induced apoptosis, and to determine the molecular mechanisms underlying the effects. Accordingly, the phosphorylation/activation of Akt and FoxO3a were analyzed by Western blot while the possible pathways involved in the protection of IGF-1 were investigated by application of various pathway inhibitors...
October 24, 2016: Molecular Neurobiology
R L Openshaw, D M Thomson, J M Penninger, J A Pratt, B J Morris
RATIONALE: Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear. OBJECTIVE: In the current study, we test the hypothesis that reduced MKK7 expression is sufficient to cause cognitive impairment. METHODS: Attentional function in mice haploinsufficient for Map2k7 (Map2k7 (+/-) mice) was investigated using the five-choice serial reaction time task (5-CSRTT)...
October 24, 2016: Psychopharmacology
Aiko Tanaka, Mie Nishimura, Yuji Sato, Hiroki Sato, Jun Nishihira
Pleurotus cornucopiae (Oyster mushroom, Tamogitake) has long been eaten as a functional food for enhancement of the immune system, but its effectiveness has not been well confirmed in humans. To this end, we set up a double-blind placebo-controlled human clinical trial to investigate the potential of Oyster mushrooms with respect to the up-regulation of the immune system. The subjects ingested Oyster mushroom extract for 8 weeks. We measured the serum cytokine levels involved in regulation of the immune system, including interferon (IFN)-γ, interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, and tumor-necrosis factor (TNF)-α...
October 2016: Journal of Traditional and Complementary Medicine
Juanjuan Zhao, Chao Chen, Mengmeng Guo, Yijin Tao, PanPan Cui, Ya Zhou, Nalin Qin, Jing Zheng, Jidong Zhang, Lin Xu
Recent evidence showed that microRNA-7 (miR-7) played an important role in the pathologies of lung-related diseases. However, the potential role of miR-7 in acute lung injury (ALI) still remains poorly understood. Here, we assessed the effect of miR-7 deficiency on the pathology of ALI. We, first, found that the expression of miR-7 was upregulated in lung tissue in murine LPS-induced ALI model. Notably, we generated miR-7 knock down mice by using miRNA-Sponge technique and found that miR-7 deficiency could ameliorate the pathologies of lung as evidenced by accelerated body weight recovery, reduced level of bronchoalveolar lavage (BAL) proinflammatory cytokines and decreased number of BAL cells in ALI mice...
2016: Frontiers in Immunology
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