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https://www.readbyqxmd.com/read/28340506/neuromedin-u-alters-bioenergetics-and-expands-the-cancer-stem-cell-phenotype-in-her2-positive-breast-cancer
#1
Vanesa G Martinez, John Crown, Richard K Porter, Lorraine O'Driscoll
Neuromedin U (NmU) is a neuropeptide belonging to the neuromedin family. Recently, we reported a significant association between NmU and breast cancer, particularly correlating with increased aggressiveness, resistance to HER2-targeted therapies and overall significantly poorer outcome for patients, although the mechanism through which it exerts this effect remained unexplained. Investigating this, here we found that ectopic over-expression of NmU in HER2-positive breast cancer cells induced aberrant metabolism, with increased glycolysis, likely due to enhanced pyruvate dehydrogenase kinase activity...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28340496/recent-developments-in-nanomedicine-for-melanoma-treatment
#2
REVIEW
Jian-Qin Tang, Xiao-Yang Hou, Chun-Sheng Yang, Ya-Xi Li, Yong Xin, Wen-Wen Guo, Zhi-Ping Wei, Yan-Qun Liu, Guan Jiang
Melanoma is a most aggressive skin cancer with limited therapeutic options and its incidence is increasing rapidly in recent years. The discovery and application of new targeted therapy agents have shown significant benefits. However, adverse side-effects and resistance to chemotherapy remain formidable challenges in the clinical treatment of malignant melanoma. Nanotherapeutics offers an important prospect of overcoming these drawbacks. The anti-tumoral applications of nanomedicine are varied, including those in chemotherapy, RNA interference, photothermal therapy, and photodynamic therapy...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28340487/microrna-4739-regulates-osteogenic-and-adipocytic-differentiation-of-immortalized-human-bone-marrow-stromal-cells-via-targeting-lrp3
#3
Mona Elsafadi, Muthurangan Manikandan, Nehad M Alajez, Rimi Hamam, Raed Abu Dawud, Abdullah Aldahmash, Zafar Iqbal, Musaad Alfayez, Moustapha Kassem, Amer Mahmood
Understanding the regulatory networks underlying lineage differentiation and fate determination of human bone marrow stromal cells (hBMSC) is a prerequisite for their therapeutic use. The goal of the current study was to unravel the novel role of the low-density lipoprotein receptor-related protein 3 (LRP3) in regulating the osteogenic and adipogenic differentiation of immortalized hBMSCs. Gene expression profiling revealed significantly higher LRP3 levels in the highly osteogenic hBMSC clone imCL1 than in the less osteogenic clone imCL2, as well as a significant upregulation of LRP3 during the osteogenic induction of the imCL1 clone...
March 8, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28340475/irinotecan-upregulates-fibroblast-growth-factor-receptor-3-expression-in-colorectal-cancer-cells-which-mitigates-irinotecan-induced-apoptosis
#4
Zeynep N Erdem, Stefanie Schwarz, Daniel Drev, Christine Heinzle, Andrea Reti, Petra Heffeter, Xenia Hudec, Klaus Holzmann, Bettina Grasl-Kraupp, Walter Berger, Michael Grusch, Brigitte Marian
BACKGROUND: Irinotecan (IRI) is an integral part of colorectal cancer (CRC) therapy, but response rates are unsatisfactory and resistance mechanisms are still insufficiently understood. As fibroblast growth factor receptor 3 (FGFR3) mediates essential survival signals in CRC, it is a candidate gene for causing intrinsic resistance to IRI. METHODS: We have used cell line models overexpressing FGFR3 to study the receptor's impact on IRI response. For pathway blockade, a dominant-negative receptor mutant and a small molecule kinase inhibitor were employed...
March 21, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28340404/synthesis-in-vitro-antiproliferative-activity-and-kinase-profile-of-new-benzimidazole-and-benzotriazole-derivatives
#5
Konrad Chojnacki, Patrycja Wińska, Katarzyna Skierka, Monika Wielechowska, Maria Bretner
Protein kinase 2 (CK2), a member of the serine/threonine kinase family, has been established as a promising target in anticancer therapy. New derivatives of known CK2 inhibitors 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) bearing azide or substituted triazole groups were synthesized. Their influence on the activity of human recombinant CK2α and cytotoxicity against normal and cancer cell lines were evaluated. TBBi derivatives with triazole substituted with carboxyl substituent (7 and 10) exhibited the most potent inhibitory activity against CK2 with Ki value in the range of 1...
March 16, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28340379/knockdown-of-ska1-gene-inhibits-cell-proliferation-and-metastasis-in-human-adenoid-cystic-carcinoma
#6
Li-Juan Zhao, Hong-Li Yang, Ke-Yi Li, Yue-Hua Gao, Kai Dong, Zhong-Hao Liu, Le-Xin Wang, Bin Zhang
The spindle and kinetochore-associated complex subunit 1(SKA1) is a newly discovered gene, which has been associated with mitosis and tumorigenesis. However, its role insalivary adenoid cystic carcinoma (SACC) is still unknown, and the invasive and metastatic mechanism in SACC is still unclear. To explore the molecular mechanism of SKA1 in the process of malignant proliferation and metastasis in adenoid cystic cancer (ACC) cells, we employed lentivirus-mediated short hairpin RNA to knockdown SKA1 in SACC-83 cells...
March 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28340378/current-fda-approved-treatments-for-non-small-cell-lung-cancer-and-potential-biomarkers-for-its-detection
#7
REVIEW
Karla A Ruiz-Ceja, Yolanda I Chirino
BACKGROUND: Lung cancer is the leading worldwide cancer with almost 1.5 million deaths every year. Some drugs for lung cancer treatment have been available on the market for decades, but novel drugs have emerged promising better outcomes, especially for Non-Small Cell Lung Cancer (NSCLC), which represents 75% of lung cancer cases. However, how much do drugs have evolved for NSCLC treatment? Are they sharing the same mechanism of action? AIM: In this review we analyzed how the approved drugs by Federal Drug Agency for NSCLC have advanced in the last four decades identifying shared mechanism of action of medicines against NSCLC treatment and some of the potential biomarkers for early detection...
March 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28340340/selective-chemical-inhibition-of-pgc-1%C3%AE-gluconeogenic-activity-ameliorates-type-2-diabetes
#8
Kfir Sharabi, Hua Lin, Clint D J Tavares, John E Dominy, Joao Paulo Camporez, Rachel J Perry, Roger Schilling, Amy K Rines, Jaemin Lee, Marc Hickey, Melissa Bennion, Michelle Palmer, Partha P Nag, Joshua A Bittker, José Perez, Mark P Jedrychowski, Umut Ozcan, Steve P Gygi, Theodore M Kamenecka, Gerald I Shulman, Stuart L Schreiber, Patrick R Griffin, Pere Puigserver
Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340257/cd8-positive-t-cell-leukoencephalitis-with-astrocytopathy-clinically-presenting-as-neuromyelitis-optica
#9
Diana L Thomas, Jody Manners, Daniel Marker, Joseph Mettenburg, Geoffrey Murdoch, Bryan Stevens, Guoji Wang, Clayton Wiley
We describe a novel disease entity with the clinical and radiologic presentation of neuromyelitis optica (NMO) and widespread CD8-positive T-cell leukoencephalitis and astrocytopathy. The 59-year-old female patient had a complex 2-year neurological history that included early changes in cognition and memory, progressive lower extremity motor dysfunction, and multimodal sensory involvement. MRI of the spinal cord showed increased T2 signal in the central cord extending from C2 through T4. MRI of the brain showed symmetric radial enhancement in periventricular deep white matter without evidence of demyelinating lesions...
March 16, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28340220/her2-neu-status-determination-in-breast-cancer-a-single-institutional-experience-using-a-dual-testing-approach-with-immunohistochemistry-and-fluorescence-in-situ-hybridization
#10
James P Solomon, Marie Dell'Aquila, Oluwole Fadare, Farnaz Hasteh
Objectives: According to current guidelines, either immunohistochemistry (IHC) or in situ hybridization (ISH) can be used to determine human epidermal growth factor receptor 2 (Her2/neu) status in breast carcinoma. While the guidelines explicitly delineate result interpretation, there is no consensus on the most appropriate testing algorithm. Methods: The Her2/neu statuses of 369 consecutive cases of invasive breast cancer (from 351 patients) were assessed in a dual-testing algorithm that uses both IHC and fluorescence ISH (FISH)...
March 11, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28340183/crlf2-positive-b-cell-acute-lymphoblastic-leukemia-in-adult-patients-a-single-institution-experience
#11
Sergej Konoplev, Xinyan Lu, Marina Konopleva, Nitin Jain, Juan Ouyang, Maitrayee Goswami, Kathryn G Roberts, Marc Valentine, Charles G Mullighan, Carlos Bueso-Ramos, Patrick A Zweidler-McKay, Jeffrey L Jorgensen, Sa A Wang
Objectives: Cytokine receptor-like factor 2 ( CRLF2 ) rearrangement is found in approximately 50% of pediatric Ph-like B-cell acute lymphoblastic leukemia (B-ALL), and around 50% of CRLF2 + cases harbor JAK mutations. We analyzed CRLF2 expression and studied its correlation with CRLF2 rearrangement in adult patients with B-ALL. Methods: Multiparameter flow cytometry (MFC) was performed consecutively in 126 patients. Results: CRLF2 overexpression was detected in 30 (27%) patients, 28 (41%) of 69 patients with B-ALL not otherwise specified, 14 (21%) of 67 untreated patients, and 16 (27%) of 59 patients with relapsed B-ALL, with the highest among Hispanic patients (25/55, 45%)...
March 13, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28340182/novel-targets-and-future-strategies-for-acute-cardioprotection-position-paper-of-the-european-society-of-cardiology-working-group-on-cellular-biology-of-the-heart
#12
Derek J Hausenloy, David Garcia-Dorado, Hans Erik Bøtker, Sean M Davidson, James Downey, Felix B Engel, Robert Jennings, Sandrine Lecour, Jonathan Leor, Rosalinda Madonna, Michel Ovize, Cinzia Perrino, Fabrice Prunier, Rainer Schulz, Joost P G Sluijter, Linda W Van Laake, Jakob Vinten-Johansen, Derek M Yellon, Kirsti Ytrehus, Gerd Heusch, Péter Ferdinandy
Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury. During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic - however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing...
March 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28340149/individual-and-regional-determinants-for-physical-therapy-utilization-in-germany-multilevel-analysis-of-national-survey-data
#13
Alexander Rommel, Lars Eric Kroll
Background: Physical therapy (PT) is included in many clinical guidelines and a commonly used health service. However, access to its benefits should not strongly depend on social or demographic factors. Objective: The present study used the Andersen model to explain to what extent PT utilization in Germany depends on factors beyond medical need. Methods: The German Health Interview and Examination Survey for Adults (DEGS, 2008-2011; target population, 18-79 years) is part of the German health-monitoring system...
March 9, 2017: Physical Therapy
https://www.readbyqxmd.com/read/28340118/group-music-therapy-as-a-preventive-intervention-for-young-people-at-risk-cluster-randomized-trial
#14
Christian Gold, Suvi Saarikallio, Alexander Hew Dale Crooke, Katrina Skewes McFerran
Background: Music forms an important part of the lives and identities of adolescents and may have positive or negative mental health implications. Music therapy can be effective for mental disorders such as depression, but its preventive potential is unknown. Objective: The aim of this study was to examine whether group music therapy (GMT) is an effective intervention for young people who may be at risk of developing mental health problems, as indicated via unhealthy music use...
March 7, 2017: Journal of Music Therapy
https://www.readbyqxmd.com/read/28340006/benefit-of-biologics-initiation-in-moderate-versus-severe-rheumatoid-arthritis-evidence-from-a-united-states-registry
#15
Arthur Kavanaugh, Edward Keystone, Jeffrey D Greenberg, George W Reed, Jenny M Griffith, Alan W Friedman, Katherine C Saunders, Arijit Ganguli
Objectives.: To compare clinical outcomes and treatment patterns among patients with moderate vs severe RA following biologic DMARD initiation. Methods.: Biologics-naive patients with moderate to severe RA [Clinical Disease Activity Index (CDAI) >10] who initiated a biologic DMARD were selected from the Corrona registry (2001-13). CDAI, functional status [modified HAQ (mHAQ)] and patterns of drug use were compared at 1 and 2 years post-initiation between patients with moderate (CDAI >10⩽22) vs severe (CDAI >22) baseline disease activity...
March 8, 2017: Rheumatology
https://www.readbyqxmd.com/read/28339918/can-clinically-relevant-dose-errors-in-patient-anatomy-be-detected-by-gamma-passing-rate-or-modulation-complexity-score-in-volumetric-modulated-arc-therapy-for-intracranial-tumors
#16
Shingo Ohira, Yoshihiro Ueda, Masaru Isono, Akira Masaoka, Misaki Hashimoto, Masayoshi Miyazaki, Masaaki Takashina, Masahiko Koizumi, Teruki Teshima
We investigated whether methods conventionally used to evaluate patient-specific QA in volumetric-modulated arc therapy (VMAT) for intracranial tumors detect clinically relevant dosimetric errors. VMAT plans with coplanar arcs were designed for 37 intracranial tumors. Dosimetric accuracy was validated by using a 3D array detector. Dose deviations between the measured and planned doses were evaluated by gamma analysis. In addition, modulation complexity score for VMAT (MCSv) for each plan was calculated. Three-dimensional dose distributions in patient anatomy were reconstructed using 3DVH software, and clinical deviations in dosimetric parameters between the 3DVH doses and planned doses were calculated...
March 3, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28339844/intensity-modulated-radiotherapy-using-two-static-ports-of-tomotherapy-for-breast-cancer-after-conservative-surgery-dosimetric-comparison-with-other-treatment-methods-and-3-year-clinical-results
#17
Aiko Nagai, Yuta Shibamoto, Masanori Yoshida, Koji Inoda, Yuzo Kikuchi
This study investigated the differences in dose-volume parameters for the breast and normal tissues during TomoDirectTM (TD) intensity-modulated radiation therapy (IMRT), TD-3D conformal radiotherapy (3DCRT) and 3DCRT plans, all using two beams, and analyzed treatment outcomes of two-beam TD-IMRT for breast cancer after breast-conserving surgery. Between August 2011 and January 2015, 152 patients were treated using two-beam TD-IMRT with 50 Gy/25 fractions. Among them, 20 patients with left-sided breast cancer were randomly chosen, and two-beam TD-IMRT, TD-3DCRT and 3DCRT plans were created for each patient...
February 23, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28339833/vdac1-is-a-molecular-target-in-glioblastoma-with-its-depletion-leading-to-reprogrammed-metabolism-and-reversed-oncogenic-properties
#18
Tasleem Arif, Yakov Kerlin, Itay Nakdimon, Daniel Benharroch, Avijit Paul, Daniela Dadon-Klein, Varda Shoshan-Barmatz
Background.: Glioblastoma (GBM), an aggressive brain tumor with frequent relapses and a high mortality, still awaits an effective treatment. Like many cancers, GBM cells acquire oncogenic properties, including metabolic reprogramming, vital for growth. As such, tumor metabolism is an emerging avenue for cancer therapy. One relevant target is the voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein controlling cell energy and metabolic homeostasis. Methods...
February 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339831/safety-of-intravenous-ferric-carboxymaltose-versus-oral-iron-in-patients-with-nondialysis-dependent-ckd-an-analysis-of-the-1-year-find-ckd-trial
#19
Simon D Roger, Carlo A Gaillard, Andreas H Bock, Fernando Carrera, Kai-Uwe Eckardt, David B Van Wyck, Maureen Cronin, Yvonne Meier, Sylvain Larroque, Iain C Macdougall
Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron...
February 27, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339776/effect-of-acute-millimeter-wave-exposure-on-dopamine-metabolism-of-ngf-treated-pc12-cells
#20
Alexis J Haas, Yann Le Page, Maxim Zhadobov, Ronan Sauleau, Yves Le Dréan, Christian Saligaut
Several forthcoming wireless telecommunication systems will use electromagnetic frequencies at millimeter waves (MMWs), and technologies developed around the 60-GHz band will soon know a widespread distribution. Free nerve endings within the skin have been suggested to be the targets of MMW therapy which has been used in the former Soviet Union. So far, no studies have assessed the impact of MMW exposure on neuronal metabolism. Here, we investigated the effects of a 24-h MMW exposure at 60.4 GHz, with an incident power density (IPD) of 5 mW/cm², on the dopaminergic turnover of NGF-treated PC12 cells...
February 24, 2017: Journal of Radiation Research
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