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Treatment resistance

Troy A Skwor, Stephanie Klemm, Hanyu Zhang, Brianna Schardt, Stephanie Blaszczyk, Matthew A Bork
Increasing rates of antibiotic resistance coupled with the lack of novel antibiotics threatens proper clinical treatment and jeopardizes their use in prevention. A photodynamic approach appears to be an innovative treatment option, even for multi-drug resistant strains of bacteria. Three components are utilized in photodynamic inactivation: a photosensitizer, light source, and oxygen. Variations in photosensitizers strongly influence microbial binding and bactericidal activity. In this study, four different cationic metalloporphyrins (Cu(2+), Fe(2+), Pd(2+), Zn(2+)) were compared to the free-base ligand 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin regarding their electronic properties and generation of reactive oxygen species upon subsequent 405nm violet-blue irradiation...
October 15, 2016: Journal of Photochemistry and Photobiology. B, Biology
Xiang-Xin Huang, Yun-Xuan Li, Xiang-Yu Li, Xiao-Xia Hu, Peng-Fei Tang, Guo-Xin Hu
Currently, crizotinib is the first generation drug, which has been used in the treatment of ALK-rearranged non-small cell lung cancer (NSCLC). However, more and more patients are found in crizotinib-resistance. In the last year, alectinib has been approved for treatment of patients with crizotinib-resistance. In this study, we aim to develop and validate a simple, rapid and sensitive tandem mass spectrometry (UHPLC-MS/MS) method for determination of alectinib in rat plasma. Diazepam was chosen as an internal standard (IS)...
October 14, 2016: Journal of Pharmaceutical and Biomedical Analysis
Cong Wu, Meng-Qing Gong, Bo-Ya Liu, Ren-Xi Zhuo, Si-Xue Cheng
To effectively reverse multiple drug resistance (MDR) in tumor treatments, a functional nano-sized drug delivery system with active targeting function and pH sensitivity was prepared for the co-delivery of multiple drug resistance inhibitors. Buthionine sulfoximine (BSO) to inhibit GSH synthesis and celecoxib (CXB) to down-regulate P-gp expression were co-loaded in polymer/inorganic hybrid nanoparticles to form buthionine sulfoximine/celecoxib@biotin-heparin/heparin/calcium carbonate/calcium phosphate nanoparticles (BSO/CXB@BNP)...
October 13, 2016: Colloids and Surfaces. B, Biointerfaces
Vineetha Mandlik, Sohan Patil, Ramanamurthy Bopanna, Sudipta Basu, Shailza Singh
Cutaneous leishmaniasis affects nearly 0.7 to 1.3 million people annually. Treatment of this disease is difficult due to lack of appropriate medication and the growing problem of drug resistance. Natural compounds such as coumarins serve as complementary therapeutic agents in addition to the current treatment modalities. In this study, we have performed an in-silico screening of the coumarin derivatives and their anti-leishmanial properties has been explored both in-vitro and in-vivo. One of the compounds (compound 2) exhibited leishmanicidal activity and to further study its properties, nanoliposomal formulation of the compound was developed...
2016: PloS One
Anita Barikian, Haytham Salti, Ammar Safar, Ziyad R Mahfoud, Ziad F Bashshur
PURPOSE: To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. METHODS: Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later...
October 20, 2016: Retina
Erik R Nelson, Shenduo Li, Margaret Kennedy, Sturgis Payne, Kelly Kilibarda, Jeffrey Groth, Michelle Bowie, Edgardo Parilla-Castellar, Gustaaf de Ridder, Paul Kelly Marcom, Matthew Lyes, Bercedis L Peterson, Michael Cook, Salvatore V Pizzo, Donald P McDonnell, Robin E Bachelder
BACKGROUND: Although most triple-negative breast cancer (TNBC) patients initially respond to chemotherapy, residual tumor cells frequently persist and drive recurrent tumor growth. Previous studies from our laboratory and others' indicate that TNBC is heterogeneous, being composed of chemo-sensitive and chemo-resistant tumor cell subpopulations. In the current work, we studied the invasive behaviors of chemo-resistant TNBC, and sought to identify markers of invasion in chemo-residual TNBC...
October 18, 2016: Oncotarget
Yoshikane Nonagase, Kimio Yonesaka, Hisato Kawakami, Satomi Watanabe, Koji Haratani, Takayuki Takahama, Naoki Takegawa, Hiroto Ueda, Junko Tanizaki, Hidetoshi Hayashi, Takeshi Yoshida, Masayuki Takeda, Yasutaka Chiba, Takao Tamura, Kazuhiko Nakagawa, Junji Tsurutani
BACKGROUND: Overexpression of heregulin, a HER3 ligand, is one mechanism that confers resistance to the anti-HER2 agents trastuzumab and lapatinib. We investigated the impact of heregulin expression on the efficacy of HER2-targeted therapeutic agents, including trastuzumab, trastuzumab emtansine (T-DM1) and lapatinib, in vitro and in vivo and evaluated the heregulin messenger RNA (mRNA) levels in specimens from patients with HER2-positive breast or gastric cancer. RESULTS: Cell proliferation and apoptosis assays demonstrated that heregulin conferred robust resistance to lapatinib and trastuzumab via HER3-Akt pathway activation followed by survivin overexpression; however, heregulin conferred minimal or no resistance to T-DM1 and paclitaxel...
October 19, 2016: Oncotarget
Abidelfatah M Nasser, Neta-Lee Benisti, Naomi Ofer, Sivan Hovers, Yeshayahu Nitzan
Advanced wastewater treatment processes are applied to prevent the environmental dissemination of pathogenic microorganisms. Giardia lamblia causes a severe disease called giardiasis, and is highly prevalent in untreated wastewater worldwide. Monitoring the microbial quality of wastewater effluents is usually based on testing for the levels of indicator microorganisms in the effluents. This study was conducted to compare the suitability of fecal coliforms, F+ coliphages and sulfide reducing clostridia (SRC) as indicators for the reduction of Giardia cysts in two full-scale wastewater treatment plants...
October 21, 2016: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
Yingying Hong, Kyle Schmidt, Danielle Marks, Samantha Hatter, Anne Marshall, Luiz Albino, Paul Ebner
Numerous studies have assessed the efficacy of phage-based methods to inhibit Salmonella contamination in food products. As with most antibacterials, bacteria can develop resistance to phage in vitro. Here, we applied a single broad-spectrum Salmonella phage, vB_SalS_SJ_2 (SJ2; 10(8) PFU; MOI = 10), to Salmonella-contaminated meat and eggs to quantify the development of resistance in actual food matrices. Treatment with a single phage significantly reduced Salmonella Typhimurium contamination in both ground pork and liquid egg at various time points...
October 21, 2016: Foodborne Pathogens and Disease
Stephanie Heinzlmeir, Denis Kudlinzki, Sridhar Sreeramulu, Susan Klaeger, Santosh Lakshmi Gande, Verena Linhard, Mathias Wilhelm, Huichao Qiao, Dominic Helm, Benjamin Ruprecht, Krishna Saxena, Guillaume Médard, Harald Schwalbe, Bernhard Kuster
The receptor tyrosine kinase EPHA2 (Ephrin type-A receptor 2) plays important roles in oncogenesis, metastasis and treatment resistance yet therapeutic targeting, drug discovery or investigation of EPHA2 biology is hampered by the lack of appropriate inhibitors and structural information. Here, we used chemical proteomics to survey 235 clinical kinase inhibitors for their kinase selectivity and identified 24 drugs with sub-micromolar affinities for EPHA2. NMR-based conformational dynamics together with nine new co-crystal structures delineated drug-EPHA2 interactions in full detail...
October 21, 2016: ACS Chemical Biology
David E Rosow, Jamal Ahmed
Importance: Adult laryngotracheal stenosis (LTS) is typically managed surgically, but some patients fail treatment because of rapid restenosis or granulation tissue formation. The need for frequent surgery or tracheostomy reduces the quality of life in these patients and poses a significant challenge for the treating physician. New adjuvant treatments are required to reduce the surgical burden of this condition. Objective: To examine whether patients with rapidly recurrent nonvasculitic LTS who fail surgical management of their stenosis (ie, requiring dilation more frequently than every 6 months) experience longer intervals between surgical procedures when receiving adjuvant treatment with low-dose methotrexate...
October 20, 2016: JAMA Otolaryngology—Head & Neck Surgery
Krisztina Janosko, Michael R Holbrook, Ricky Adams, Jason Barr, Laura Bollinger, Je T'aime Newton, Corrie Ntiforo, Linda Coe, Jiro Wada, Daniela Pusl, Peter B Jahrling, Jens H Kuhn, Matthew G Lackemeyer
Biosafety level 4 (BSL-4) suit laboratories are specifically designed to study high-consequence pathogens for which neither infection prophylaxes nor treatment options exist. The hallmarks of these laboratories are: custom-designed airtight doors, dedicated supply and exhaust airflow systems, a negative-pressure environment, and mandatory use of positive-pressure ("space") suits. The risk for laboratory specialists working with highly pathogenic agents is minimized through rigorous training and adherence to stringent safety protocols and standard operating procedures...
October 3, 2016: Journal of Visualized Experiments: JoVE
Tabitha Bucher, Elena Kartvelishvily, Ilana Kolodkin-Gal
This work assesses different methodologies to study the impact of small molecule biofilm inhibitors, such as D-amino acids, on the development and resilience of Bacillus subtilis biofilms. First, methods are presented that select for small molecule inhibitors with biofilm-specific targets in order to separate the effect of the small molecule inhibitors on planktonic growth from their effect on biofilm formation. Next, we focus on how inoculation conditions affect the sensitivity of multicellular, floating B...
October 9, 2016: Journal of Visualized Experiments: JoVE
David Feifel, Katherine Pappas
Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1-coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils...
October 4, 2016: Journal of Visualized Experiments: JoVE
Stacey Bagby, Wells A Messersmith, Todd M Pitts, Anna Capasso, Marileila Varella-Garcia, Peter J Klauck, Jihye Kim, Aik-Choon Tan, S Gail Eckhardt, John J Tentler, John Arcaroli
Patient derived tumor xenograft (PDTX) models provide a necessary platform in facilitating anti-cancer drug development prior to human trials. Human tumor pieces are injected subcutaneously into athymic nude mice (immunocompromised, T cell deficient) to create a bank of tumors and subsequently are passaged into different generations of mice in order to maintain these tumors from patients. Importantly, cellular heterogeneity of the original tumor is closely emulated in this model, which provides a more clinically relevant model for evaluation of drug efficacy studies (single agent and combination), biomarker analysis, resistant pathways and cancer stem cell biology...
September 30, 2016: Journal of Visualized Experiments: JoVE
Helena Lenasi, Markos Klonizakis
Diabetes mellitus (DM) is associated with cardiovascular complications. Impairment of glycemic control induces noxious glycations, an increase in oxydative stress and dearangement of various metabolic pathways. DM leads to dysfunction of micro and macrovessels, connected to metabolic, endothelial and autonomic nervous system. Thus, assessing vascular reactivity might be one of the clinical tools to evaluate the impact of harmful effects of DM and potential benefit of treatment; skin and skeletal muscle microcirculation have usually been tested...
October 18, 2016: Clinical Hemorheology and Microcirculation
Brent M Egan, Bo Kai, C Shaun Wagner, Douglas O Fleming, Joseph H Henderson, Archie H Chandler, Angelo Sinopoli
Apparent treatment-resistant hypertension (aTRH) may confound the reported relationship between low blood pressure (BP) and increased cardiovascular disease (CVD) in treated hypertensive patients. Incident CVD was assessed in treated hypertensive patients with and without aTRH (BP ≥140 and/or ≥90 mm Hg on ≥3 medications or <140/<90 mm Hg on ≥4 BP medications) at three BP levels: 1: <120 and/or <70 mm Hg and <140/<90 mm Hg; 2: 120-139/70-89 mm Hg; and 3: ≥140 and/or ≥90 mm Hg. Electronic health data were matched to emergency and hospital claims for incident CVD in 118 356 treated hypertensive patients...
October 21, 2016: Journal of Clinical Hypertension
Erlin Zhang, Jing Ren, Shengyi Li, Lei Yang, Gaowu Qin
Ti-Cu sintered alloys have shown good antibacterial abilities. However, the sintered method (powder metallurgy) is not convenient to produce devices with a complex structure. In this paper, Ti-Cu alloys with 2.0, 3.0 and 4.0 wt.% Cu were prepared in an arc melting furnace and subjected to different heat treatments: solid solution and ageing, to explore the possibility of preparing an antibacterial Ti-Cu alloy by a casting method and to examine the effect of Cu content. Phase identification was conducted on an XRD diffraction meter, and the microstructure was observed by a metallographic microscope, a scanning electron microscope (SEM) with energy disperse spectroscopy (EDS) and transmission electron microscopy (TEM)...
October 21, 2016: Biomedical Materials
Sara S Franco, Karolina Szczesna, Maria S Iliou, Mohammed Al-Qahtani, Ali Mobasheri, Julianna Kobolák, András Dinnyés
Cancer cells, stem cells and cancer stem cells have for a long time played a significant role in the biomedical sciences. Though cancer therapy is more effective than it was a few years ago, the truth is that still none of the current non-surgical treatments can cure cancer effectively. The reason could be due to the subpopulation called "cancer stem cells" (CSCs), being defined as those cells within a tumour that have properties of stem cells: self-renewal and the ability for differentiation into multiple cell types that occur in tumours...
September 30, 2016: BMC Cancer
Matteo Bassetti, Alessia Carnelutti, Maddalena Peghin
The isolation of multi-drug-resistant gram-negative (MDRGN) pathogens has progressively increased worldwide and has been associated with important delays in the prescription of an adequate antibiotic treatment, resulting in increased mortality rates. Patient's stratification for MDRGN infections to optimize the prescription of an adequate empiric antimicrobial regimen is crucial. Areas covered: This article covers MDRGN epidemiology, with a specific focus on risk factors for harbouring infections sustained by extended-spectrum-Beta-lactamase (ESBL), carbapenem resistant Enterobacteriacae (CRE), MDR Pseudomonas aeruginosa and MDR Acinetobacter baumanii...
October 21, 2016: Expert Review of Anti-infective Therapy
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