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Combination Therapy

Justin Ma, Peter Lwigale
Purpose: Defects in neural crest development are a major contributing factor in corneal dysgenesis, but little is known about the genetic landscape during corneal development. The purpose of this study was to provide a detailed transcriptome profile and evaluate changes in gene expression during mouse corneal development. Methods: RNA sequencing was used to uncover the transcriptomic profile of periocular mesenchyme (pNC) isolated at embryonic day (E) 10.5 and corneas isolated at E14...
February 1, 2019: Investigative Ophthalmology & Visual Science
Ana Lúcia Bertarello Zeni, Anderson Camargo, Ana Paula Dalmagro
Depression is a neuropsychiatry medical condition with high prevalence, in which the hypothalamic-pituitary-adrenal axis dysfunction has been postulated as the main cause. The glucocorticoids can be harmful to the brain, particularly by induction of oxidative stress and glutamatergic damage, therefore antioxidants or neuroprotective agents could have beneficial effects. Lutein (LUT) is a dietary xanthophyll able to arrive in the brain that has been used for therapy of macular degeneration. In this sense, several studies pointed beneficial effects of LUT in the brain, particularly in the hippocampus and prefrontal cortex, key regions in mood regulation...
February 17, 2019: Pharmacology, Biochemistry, and Behavior
Aditya Bardia, Ingrid A Mayer, Linda T Vahdat, Sara M Tolaney, Steven J Isakoff, Jennifer R Diamond, Joyce O'Shaughnessy, Rebecca L Moroose, Alessandro D Santin, Vandana G Abramson, Nikita C Shah, Hope S Rugo, David M Goldenberg, Ala M Sweidan, Robert Iannone, Sarah Washkowitz, Robert M Sharkey, William A Wegener, Kevin Kalinsky
BACKGROUND: Standard chemotherapy is associated with low response rates and short progression-free survival among patients with pretreated metastatic triple-negative breast cancer. Sacituzumab govitecan-hziy is an antibody-drug conjugate that combines a humanized monoclonal antibody, which targets the human trophoblast cell-surface antigen 2 (Trop-2), with SN-38, which is conjugated to the antibody by a cleavable linker. Sacituzumab govitecan-hziy enables delivery of high concentrations of SN-38 to tumors...
February 21, 2019: New England Journal of Medicine
Hsiao Hsin Sung Hsieh, Shailesh Agarwal, David J Cholok, Shawn J Loder, Kieko Kaneko, Amanda Huber, Michael T Chung, Kavitha Ranganathan, Joe Habbouche, John Li, Jonathan Butts, Jonathan Reimer, Arminder Kaura, James Drake, Christopher Breuler, Caitlin R Priest, Joe Nguyen, Cameron Brownley, Jonathan Peterson, Serra Ucer Ozgurel, Yashar S Niknafs, Shuli Li, Maiko Inagaki, Greg Scott, Paul Krebsbach, Michael T Longaker, Kenneth Westover, Nathanael Gray, Jun Ninomiya-Tsuji, Yuji Mishina, Benjamin Levi
Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of TGF-β activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by re-activation to elicit differentiation and extracellular matrix (ECM) production...
February 20, 2019: Stem Cells
Andreas Pinter, Dagmar Wilsmann-Theis, Wiebke K Peitsch, Rotraut Mössner
Palmoplantar pustular psoriasis, also termed palmoplantar pustulosis (PPP), is a rare disease affecting the palmoplantar regions characterized by sterile, yellow to brown pustules mostly on erythematous skin. PPP is related to a high burden due to painful, impaired and stigmatizing character. Several isoforms of interleukin (IL) have been implicated in its pathophysiology. Here, we report on four patients with PPP treated with the novel IL-17 receptor A blocker brodalumab, in whom this therapy was not successful or showed moderate improvement combined with adverse events...
February 20, 2019: Journal of Dermatology
Amir Salek Farrokhi, Narges Darabi, Bahman Yousefi, Rafee Habib Askandar, Mansoreh Shariati, Majid Eslami
Recent studies demonstrated that a combination of the gut microbiome has the vital effect on the efficacy of anticancer immune therapies. Regulatory effects of microbiota have been shown in different types of cancer therapies such as chemotherapy and immunotherapy. Immune-checkpoint-blocked therapies are the recent efficient cancer immunotherapy strategies. The target of immune-checkpoint blocking is cytotoxic T lymphocyte protein-4 (CTLA-4) or blockade of programmed death-1 (PD-1) protein and its ligand programmed death ligand 1 (PD-L1) that they have been considered as cancer immunotherapy in recent years...
February 20, 2019: Journal of Cellular Physiology
David G P van IJzendoorn, Karoly Szuhai, Inge H Briaire-de Bruijn, Marie Kostine, Marieke L Kuijjer, Judith V M G Bovée
Based on morphology it is often challenging to distinguish between the many different soft tissue sarcoma subtypes. Moreover, outcome of disease is highly variable even between patients with the same disease. Machine learning on transcriptome sequencing data could be a valuable new tool to understand differences between and within entities. Here we used machine learning analysis to identify novel diagnostic and prognostic markers and therapeutic targets for soft tissue sarcomas. Gene expression data was used from the Cancer Genome Atlas, the Genotype-Tissue Expression data and the French Sarcoma Group...
February 20, 2019: PLoS Computational Biology
Ulrike Nitz, Oleg Gluz, Michael Clemens, Wolfram Malter, Toralf Reimer, Benno Nuding, Bahriye Aktas, Andrea Stefek, Anke Pollmanns, Fatemeh Lorenz-Salehi, Christoph Uleer, Petra Krabisch, Sherko Kuemmel, Cornelia Liedtke, Steven Shak, Rachel Wuerstlein, Matthias Christgen, Ronald E Kates, Hans H Kreipe, Nadia Harbeck
PURPOSE: The West German Study Group PlanB trial evaluated an anthracycline-free chemotherapy standard (six cycles of docetaxel and cyclophosphamide [TC]) in the routine treatment of human epidermal growth factor receptor 2-negative early breast cancer (EBC). PATIENTS AND METHODS: Patients with pT1 to pT4c, all pN+, and pN0/high-risk EBC were eligible. High-risk pN0 was defined by one or more of the following: pT greater than 2, grade 2 to 3, high urokinase-type plasminogen activator/plasminogen activator inhibitor-1, hormone receptor (HR) negativity, and less than 35 years of age...
February 20, 2019: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Wen Sun, Xueze Zhao, Jiangli Fan, Jianjun Du, Xiaojun Peng
As traditional phototherapy agents, boron dipyrromethene (BODIPY) photosensitizers have attracted increasing attention due to their high molar extinction coefficients, high phototherapy efficacy, and excellent photostability. After being formed into nanostructures, BODIPY-containing nano-photosensitizers show enhanced water solubility and biocompatibility as well as efficient tumor accumulation compared to BODIPY molecules. Hence, BODIPY nano-photosensitizers demonstrate a promising potential for fighting cancer...
February 20, 2019: Small
Tina Vilsbøll, Thomas C Blevins, Esteban Jodar, Neil Poulter, Nikolaos Tentolouris, Bue F Ross Agner, Lucine Lehmann, Lawrence A Leiter
This post hoc analysis investigated effects of insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus comparators on cardiovascular (CV) risk markers from DUAL II (versus insulin degludec), DUAL V (versus insulin glargine 100 units/mL) and DUAL VII (versus basal-bolus therapy) in patients grouped by sex, age (<65 years, ≥65 years) and diabetes duration (<10 years, ≥10 years). Treatment contrasts were in favour of IDegLira in many subgroups for changes from baseline in HbA1c (DUAL II, DUAL V), body weight (all three trials), systolic blood pressure (BP; all three trials), high-density lipoprotein cholesterol (DUAL VII) and low-density lipoprotein cholesterol (LDL-C; DUAL II, DUAL V)...
February 20, 2019: Diabetes, Obesity & Metabolism
Gabriel E Molina, Saami Khalifian, Jamie L Mull, Lu Chen, Ilana S Rosman, Beverly E Faulkner-Jones, Kenneth H Ngo, Shadmehr Demehri, Lynn A Cornelius, Peggy A Wu
Importance: Extramammary Paget disease (EMPD), a rare intraepithelial adenocarcinoma, poses a therapeutic challenge with high postoperative recurrence rates and a limited number of effective local treatment options. Objective: To describe the use and efficacy of a topical combination of fluorouracil and calcipotriene as a palliative therapy for refractory EMPD. Design, Setting, and Participants: This retrospective case series of 3 women with recurrent, refractory EMPD was conducted at Beth Israel Deaconess Medical Center, Boston, Massachusetts and Washington University School of Medicine, St Louis, Missouri...
February 20, 2019: JAMA Dermatology
Jussi Seppälä, Ilaria De Vita, Timo Jämsä, Jouko Miettunen, Matti Isohanni, Katya Rubinstein, Yoram Feldman, Eva Grasa, Iluminada Corripio, Jesus Berdun, Enrico D'Amico, Maria Bulgheroni
BACKGROUND: Mobile Therapeutic Attention for Patients with Treatment-Resistant Schizophrenia (m-RESIST) is an EU Horizon 2020-funded project aimed at designing and validating an innovative therapeutic program for treatment-resistant schizophrenia. The program exploits information from mobile phones and wearable sensors for behavioral tracking to support intervention administration. OBJECTIVE: To systematically review original studies on sensor-based mHealth apps aimed at uncovering associations between sensor data and symptoms of psychiatric disorders in order to support the m-RESIST approach to assess effectiveness of behavioral monitoring in therapy...
February 20, 2019: JMIR Mental Health
Daniele Roberto Giacobbe, Silvia Corcione, Antonio Salsano, Filippo Del Puente, Simone Mornese Pinna, Francesco Giuseppe De Rosa, Malgorzata Mikulska, Francesco Santini, Claudio Viscoli
Patients undergoing open-heart surgery may suffer from postoperative complications, including severe infections. Antimicrobials to treat infectious complications in this population should be selected thoughtfully, taking into account three different and fundamental issues: (i) the site of infection; (ii) the suspected or proven causative agent and its susceptibility pattern; and (iii) the risk of suboptimal pharmacokinetic characteristics and potential toxicity of the chosen drug/s. Areas covered: The present narrative review summarizes the current and future antimicrobial options for the treatment of infections developing after open-heart surgery...
February 20, 2019: Expert Opinion on Pharmacotherapy
Man Ye, Jun Zhou, Yixin Zhong, Jie Xu, Jingxin Hou, Xingyue Wang, Zhi-Gang Wang, Dajing Guo
Atherosclerosis is a major cause of sudden death and myocardial infarction, instigated by unstable plaques. Thus, the early detection of unstable plaques and corresponding treatment can improve the prognosis and reduce mortality. In this study, we describe a protocol for the preparation of nanoparticles (NPs) combined with the phase transitional material perfluorohexane (PFH) and with dextran sulfate (DS) targeting class A scavenger receptors (SR-A) for the diagnosis and treatment of atherosclerotic vulnerable plaques...
February 20, 2019: ACS Applied Materials & Interfaces
Christie Joya, Seung Hyun Won, Christina Schofield, Tahaniyat Lalani, Ryan C Maves, Karl Kronmann, Robert Deiss, Jason Okulicz, Brian K Agan, Anuradha Ganesan
BACKGROUND: Whether persistent low level viremia (pLLV) predicts virologic failure (VF) is unclear. We used data from the U.S. Military HIV Natural History Study (NHS), to examine the association of pLLV and VF. METHODS: NHS subjects who initiated combination antiretroviral therapy (ART) after 1996 were included if they had two or more VLs measured with a lower limit of detection of <50 copies/mL. VF was defined as a confirmed VL ≥200 copies/mL or any VL>1000 copies/mL...
February 16, 2019: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Wenbei Han, Qian Ma, Yinglu Liu, Wei Wu, Yue Tu, Lu Huang, Yan Long, Wenwen Wang, Hongyun Yee, Ziyue Wan, Renmao Tang, Yigang Wan, Haitao Tang
BACKGROUND: Huangkui capsule (HKC), an anti-inflammatory Chinese modern patent medicine, has been now widely applied to the clinical therapy of diabetic nephropathy (DN). However, the overall therapeutic mechanisms in vivo are still unclear. Renal tubular epithelial-to-mesenchymal transition (EMT) is one of the major pathogenesis of renal interstitial fibrosis in DN. Recently, the physiological roles of NLRP3 inflammasome activation and toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling are closely linked to EMT...
December 17, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Xiaodong Guan, Ye Tian, Jiafang Song, Dawei Zhu, Luwen Shi
BACKGROUND: Irrational prescriptions of antibiotics have received significant international attention. In China, previous studies have described the impact of physicians' knowledge on antibiotic use, however, empirical studies of the relationship between physician knowledge and antibiotic prescription behavior are limited. OBJECTIVE: This study aimed to examine physicians' knowledge of antibiotic and explore the effects of physicians' knowledge on rational antibiotic use in county hospitals in China...
January 30, 2019: Social Science & Medicine
Xueke Sun, Jiao Sun, Biao Dong, Gaosheng Huang, Li Zhang, Wanhui Zhou, Jiekai Lv, Xinran Zhang, Min Liu, Lin Xu, Xue Bai, Wen Xu, Yudan Yang, Xiuling Song, Hongwei Song
Accurate treatment of photothermal therapy (PTT) is crucial to avoid the unnecessary injury of normal cells and tissues. Therefore the real-time temperature monitoring in the PTT process has drawn more and more attention in recent years. Herein, we designed and prepared one kind of lanthanide (Ln3+ )-doped up-conversion nanocomposites with multi-functions, which can not only provide temperature feedback in PTT process, but also play the photodynamic therapy (PDT) function for the synergistic effect of tumor therapy...
February 14, 2019: Biomaterials
V Maisnar, Z Stefanikova, I Spicka, L Pour, J Minarik, M Flochova, J Radocha, E Gregora, N Stecova, T Jelinek, A Jungova, E Kralikova, L Brozova, R Hajek
Lenalidomide (LEN) is an immunomodulator with clinical activity against myeloma cells. Based on the pivotal phase 3 trials MM-009 and MM010, the combination of lenalidomide and dexamethasone(DEX) was approved for patients with multiple myeloma who received at least one prior therapy. Here, we evaluated LEN/DEX therapy in whole population and subsequently in selected sub-groups of patients with relapsed/refractory multiple myeloma followed in the Monoclonal Gammopathy Registry of the Czech Myeloma Group. 858 patients were treated with LEN/DEX in Czech Republic and Slovakia until end of 2017...
February 20, 2019: Neoplasma
Yann Cormerais, Marina Pagnuzzi-Boncompagni, Sandra Schrötter, Sandy Giuliano, Eric Tambutté, Hitoshi Endou, Michael F Wempe, Gilles Pagès, Jacques Pouysségur, Vincent Picco
Most cases of medulloblastoma (MB) occur in young children. While the overall survival rate can be relatively high, current treatments combining surgery, chemo- and radiotherapy are very destructive for patient development and quality of life. Moreover, aggressive forms and recurrences of MB cannot be controlled by classical therapies. Therefore, new therapeutic approaches yielding good efficacy and low toxicity for healthy tissues are required to improve patient outcome. Cancer cells sustain their proliferation by optimizing their nutrient uptake capacities...
February 19, 2019: Journal of Cellular and Molecular Medicine
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