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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/28340475/irinotecan-upregulates-fibroblast-growth-factor-receptor-3-expression-in-colorectal-cancer-cells-which-mitigates-irinotecan-induced-apoptosis
#3
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/28340175/funresdb-a-web-resource-for-genotypic-susceptibility-testing-of-aspergillus-fumigatus
#4
Michael Weber, Jonas Schaer, Grit Walther, Kerstin Kaerger, Jörg Steinmann, Peter-Michael Rath, Birgit Spiess, Dieter Buchheidt, Axel Hamprecht, Oliver Kurzai
Therapy of invasive aspergillosis is becoming more difficult due to the emergence of azole resistance in Aspergillus fumigatus. A majority of resistant strains carries mutations in the CYP51A gene. Due to a lack of sensitivity of culture-based methods, molecular detection of A. fumigatus has become an important diagnostic tool. We set up the database FunResDB (www.nrz-myk.de/funresdb) to gather all available information about CYP51A-dependent azole resistance from published literature. In summary, the screening resulted in 79 CYP51A variants, which are linked to 59 nonsynonymous mutations...
March 11, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28340122/potential-role-of-patients-cyp3a-status-in-clozapine-pharmacokinetics
#5
Katalin Tóth, Gábor Csukly, Dávid Sirok, Ales Belic, Ádám Kiss, Edit Háfra, Máté Déri, Ádám Menus, István Bitter, Katalin Monostory
Background: The atypical antipsychotic clozapine is effective in treatment-resistant schizophrenia; however, the success or failure of clozapine therapy is substantially affected by the variables that impact the clozapine blood concentration. Thus, elucidating the inter-individual differences in clozapine pharmacokinetics can facilitate the personalized therapy. Methods: Since potential role in clozapine metabolism is assigned to CYP1A2, CYP2C19, CYP2D6 and CYP3A enzymes, the association between the patients' CYP-status (CYP genotypes, CYP expression) and clozapine clearance was evaluated in 92 psychiatric patients...
March 18, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28339788/intravenous-dendritic-cell-administration-enhances-suppression-of-lung-metastasis-induced-by-carbon-ion-irradiation
#6
Ken Ando, Hidetoshi Fujita, Akihiro Hosoi, Liqiu Ma, Masaru Wakatsuki, Ken-Ichiro Seino, Kazuhiro Kakimi, Takashi Imai, Takashi Shimokawa, Takashi Nakano
Carbon-ion radiotherapy (CIRT) is an advanced radiotherapy and has achieved good local control, even in tumors that are resistant to conventional photon beam radiotherapy (PBRT). However, distant metastasis control is an important issue. Recently, the combination of radiotherapy and immunotherapy has attracted the attention. In immunotherapy, dendritic cells (DCs) play a pivotal role in the anti-tumor immune system. However, the mechanisms underlying the combination therapy of DCs and radiotherapy have been unclear...
February 27, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28339594/in-vivo-development-of-fluconazole-resistance-in-serial-cryptococcus-gattii-isolates-from-a-cat
#7
Jane E Sykes, Greg Hodge, Anil Singapuri, Mai Lee Yang, Angie Gelli, George R Thompson
Elevated fluconazole minimum inhibitory concentrations (MICs) are more frequently observed in Cryptococcus gattii compared to C. neoformans isolates; however, the development of in vivo resistance and the molecular mechanisms responsible have not been reported for this species. We report a case of Cryptococcus gattii (molecular type VGIII) that developed reduced susceptibility to fluconazole during therapy and delineate the molecular mechanisms responsible. Multilocus sequence typing and quantitative DNA analysis of the pre- and post-treatment isolates was performed using well-characterized methods...
October 7, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28339582/hypoxia-in-the-glioblastoma-microenvironment-shaping-the-phenotype-of-cancer-stem-like-cells
#8
Nicole Colwell, Mioara Larion, Amber J Giles, Ashlee N Seldomridge, Saman Sizdahkhani, Mark R Gilbert, Deric M Park
Glioblastoma is the most common and aggressive malignant primary brain tumor. Cellular heterogeneity is a characteristic feature of the disease and contributes to the difficulty in formulating effective therapies. Glioma stem-like cells (GSCs) have been identified as a subpopulation of tumor cells that are thought to be largely responsible for resistance to treatment. Intratumoral hypoxia contributes to maintenance of the GSCs by supporting the critical stem cell traits of multipotency, self-renewal, and tumorigenicity...
January 19, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28335413/chitin-oligosaccharide-cos-reduces-antibiotics-dose-and-prevents-antibiotics-caused-side-effects-in-adolescent-idiopathic-scoliosis-ais-patients-with-spinal-fusion-surgery
#9
Yang Qu, Jinyu Xu, Haohan Zhou, Rongpeng Dong, Mingyang Kang, Jianwu Zhao
Antibiotics are always considered for surgical site infection (SSI) in adolescent idiopathic scoliosis (AIS) surgery. However, the use of antibiotics often causes the antibiotic resistance of pathogens and side effects. Thus, it is necessary to explore natural products as drug candidates. Chitin Oligosaccharide (COS) has anti-inflammation and anti-bacteria functions. The effects of COS on surgical infection in AIS surgery were investigated. A total of 312 AIS patients were evenly and randomly assigned into control group (CG, each patient took one-gram alternative Azithromycin/Erythromycin/Cloxacillin/Aztreonam/Ceftazidime or combined daily), experiment group (EG, each patient took 20 mg COS and half-dose antibiotics daily), and placebo group (PG, each patient took 20 mg placebo and half-dose antibiotics daily)...
March 14, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28335039/brain-temporal-complexity-in-explaining-the-therapeutic-and-cognitive-effects-of-seizure-therapy
#10
Faranak Farzan, Sravya Atluri, Ye Mei, Sylvain Moreno, Andrea J Levinson, Daniel M Blumberger, Zafiris J Daskalakis
Over 350 million people worldwide suffer from depression, a third of whom are medication-resistant. Seizure therapy remains the most effective treatment in depression, even when many treatments fail. The utility of seizure therapy is limited due to its cognitive side effects and stigma. The biological targets of seizure therapy remain unknown, hindering design of new treatments with comparable efficacy. Seizures impact the brains temporal dynamicity observed through electroencephalography. This dynamicity reflects richness of information processing across distributed brain networks subserving affective and cognitive processes...
March 3, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334886/glioblastoma-associated-microglia-and-macrophages-targets-for-therapies-to-improve-prognosis
#11
Candice C Poon, Susobhan Sarkar, V Wee Yong, John J P Kelly
Glioblastoma is the most common and most malignant primary adult human brain tumour. Diagnosis of glioblastoma carries a dismal prognosis. Treatment resistance and tumour recurrence are the result of both cancer cell proliferation and their interaction with the tumour microenvironment. A large proportion of the tumour microenvironment consists of an inflammatory infiltrate predominated by microglia and macrophages, which are thought to be subverted by glioblastoma cells for tumour growth. Thus, glioblastoma-associated microglia and macrophages are logical therapeutic targets...
February 4, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334734/multinucleated-polyploidy-drives-resistance-to-docetaxel-chemotherapy-in-prostate-cancer
#12
Karuna Mittal, Shashi Donthamsetty, Ramneet Kaur, Chunhua Yang, Meenakshi V Gupta, Michelle D Reid, Da Hoon Choi, Padmashree C G Rida, Ritu Aneja
BACKGROUND: Docetaxel is the only FDA-approved first-line treatment for castration-resistant prostate cancer (CRPC) patients. Docetaxel treatment inevitably leads to tumour recurrence after an initial therapeutic response with generation of multinucleated polyploid (MP) cells. Here we investigated role of MP cells in clinical relapse of CRPC. METHODS: Prostate cancer (PC-3) cells were treated with docetaxel (5 nM) for 3 days followed by a washout and samples were collected at close intervals over 35 days post drug washout...
March 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28334732/high-stmn1-level-is-associated-with-chemo-resistance-and-poor-prognosis-in-gastric-cancer-patients
#13
Tuya Bai, Takehiko Yokobori, Bolag Altan, Munenori Ide, Erito Mochiki, Mitsuhiro Yanai, Akiharu Kimura, Norimichi Kogure, Toru Yanoma, Masaki Suzuki, Pinjie Bao, Kyoichi Kaira, Takayuki Asao, Ayaka Katayama, Tadashi Handa, Navchaa Gombodorj, Masahiko Nishiyama, Tetsunari Oyama, Kyoichi Ogata, Hiroyuki Kuwano
BACKGROUND: Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. Despite several reports, its roles in gastric cancer (GC) remain unclear owing to a lack of analyses of highly metastatic cases. This study aimed to investigate STMN1 as a prognostic and predictive indicator of response to paclitaxel therapy in patients with GC, including inoperable cases. METHODS: Immunohistochemical analysis of STMN1 was performed on both operable (n=95) and inoperable GC (n=61) samples...
March 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28334683/combined-metformin-and-insulin-treatment-reverses-metabolically-impaired-omental-adipogenesis-and-accumulation-of-4-hydroxynonenal-in-obese-diabetic-patients
#14
Morana Jaganjac, Shamma Almuraikhy, Fatima Al-Khelaifi, Mashael Al-Jaber, Moataz Bashah, Nayef A Mazloum, Kamelija Zarkovic, Neven Zarkovic, Georg Waeg, Wael Kafienah, Mohamed A Elrayess
OBJECTIVE: Obesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype. METHODS: OM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery...
March 16, 2017: Redox Biology
https://www.readbyqxmd.com/read/28334546/-parathyroid-cancer
#15
Ivana Ságová, Matej Stančík, Peter Kentoš, Dušan Pavai, Daniela Kantárová, Anton Vaňuga, Peter Vaňuga
Parathyroid cancer is a rare endocrine malignancy, representing less than 1 % of all cases of primary hyperparathyroidism. The exact etiology of the disease remains unknown. Known risk factors include neck irradiation, end stage renal failure, genetic factors, particularly the the HPRT2/CDCT73 gene mutation. The clinical picture is often indolent, yet progressive with a trend of local invasion and metastasis formation in advanced disease. The clinical picture includes symptoms of severe and resistant hypercalcemia, requiring intensive therapy often with the need of dialysis...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28334499/dorsal-column-stimulation-versus-dorsal-root-ganglion-stimulation-for-complex-regional-pain-syndrome-confined-to-the-knee-patients-preference-following-the-trial-period
#16
Catelijne M van Bussel, Dirk L Stronks, Frank J P M Huygen
BACKGROUND AND OBJECTIVES: Patients with complex regional pain syndrome (CRPS) confined to the knee are often therapy resistant. Neurostimulation is an accepted treatment for CRPS. Although results with dorsal column (DC) stimulation in patients with CRPS confined to the knee are often disappointing, the availability of dorsal root ganglion (DRG) stimulation may provide new opportunities for this complaint. Therefore, this study explores patients' preference for DC stimulation vs. DRG stimulation in treating chronic pain due to CRPS confined to the knee...
March 23, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/28334049/mmp1-expression-is-activated-by-slug-and-enhances-multi-drug-resistance-mdr-in-breast-cancer
#17
Ching-Ju Shen, Yu-Ling Kuo, Chien-Chung Chen, Ming-Jenn Chen, Ya-Min Cheng
High matrix metalloproteinase 1 (MMP1) expression is associated with enhanced breast cancer growth and metastasis and also might predict poor prognosis. In this study, we further investigated the functional role of MMP1 and how it is upregulated in multi-drug resistant (MDR) breast cancer cells. By retrieving microarray data in GEO datasets and the survival data in the Kaplan Meier plotter, we observed that MMP1 is significantly upregulated in MCF-7/ADR cells compared to the parental MCF-7 cells, while high MMP1 expression is associated with worse overall survival (OS) and recurrence free survival (RFS) in breast cancer patients after systematic therapy...
2017: PloS One
https://www.readbyqxmd.com/read/28333921/bioenergetics-based-modeling-of-plasmodium-falciparum-metabolism-reveals-its-essential-genes-nutritional-requirements-and-thermodynamic-bottlenecks
#18
Anush Chiappino-Pepe, Stepan Tymoshenko, Meriç Ataman, Dominique Soldati-Favre, Vassily Hatzimanikatis
Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa) of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA). Using previous absolute concentration data of the intraerythrocytic parasite, we applied TFA to iPfa and predicted up to 63 essential genes and 26 essential pairs of genes...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28333351/ecological-impact-of-ciprofloxacin-on-commensal-enterococci-in-healthy-volunteers
#19
Victoire de Lastours, Elena Maugy, Vincent Mathy, Françoise Chau, Benjamin Rossi, François Guérin, Vincent Cattoir, Bruno Fantin
Background: The ecological impact of ciprofloxacin on commensal enterococci is unknown. Methods: Forty-eight healthy volunteers received ciprofloxacin from day (D) 0 to D14; stools were collected on D7, D14 and D42. Fluoroquinolone-susceptible and -resistant enterococci (FQ-SE and FQ-RE) were detected and quantified by culture, and identified by MALDI-TOF MS. The relative abundance of FQ-RE over FQ-SE was determined. The genetic basis of fluoroquinolone resistance was deciphered by partial sequencing of gyrA and parC genes...
March 4, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28333335/saccharomyces-boulardii-cncm-i-745-restores-intestinal-barrier-integrity-by-regulation-of-e-cadherin-recycling
#20
Chloé Terciolo, Aurélie Dobric, Mehdi Ouaissi, Carole Siret, Gilles Breuzard, Françoise Silvy, Bastien Marchiori, Sébastien Germain, Renaté Bonier, Adel Hama, Roisin Owens, Dominique Lombardo, Véronique Rigot, Frédéric André
Background and Aims: Alteration in intestinal permeability is the main factor underlying the pathogenesis of many diseases affecting the gut, such as inflammatory bowel disease (IBD). Characterization of molecules targeting the restoration of intestinal barrier integrity is therefore vital for the development of alternative therapies. The yeast Saccharomyces boulardii CNCM I-745 (Sb), used to prevent and treat antibiotic-associated infectious and functional diarrhea, may have a beneficial effect in the treatment of IBD...
February 22, 2017: Journal of Crohn's & Colitis
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