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Therapeutic effect

Fady Rachid
Major depressive disorder is a highly prevalent and profoundly disabling psychiatric disorder with significant morbidity and mortality and it is very often resistant to antidepressants, electroconvulsive therapy and psychotherapy. Therapeutic alternatives include repetitive transcranial magnetic stimulation which may be an effective choice for treatment-resistant depression but requires prolonged treatments for at least four to six weeks. Shorter exposure to this technique might be more advantageous for certain cases...
February 8, 2019: Asian Journal of Psychiatry
Annika Klimpel, Tamara Lützenburg, Ines Neundorf
Cancer is one of the major growing public health problems making the development of new anti-cancer treatment strategies still compulsory. Conventionally used chemotherapies are quite often associated with severe side effects. One reason is limited cell-permeability of the used drugs resulting in only poor overall bioavailability. During the last thirty years, cell-penetrating peptides (CPPs) have extensively been studied as efficient vehicles for several classes of cargos, and the development of novel therapeutic applications including CPPs has gained a major role in current cancer research...
February 13, 2019: Current Opinion in Pharmacology
Alison E Vickman, Nicola L B Pohl
Deoxysugars are intrinsic components in a number of antibiotics, antimicrobials, and therapeutic agents that often dictate receptor binding, improve efficacy, and provide a diverse toolbox in modifying glycoconjugate function due to an extensive number of unique isomers and inherent conformational flexibility. Hence, this work provides a comprehensive examination of the conformational effects associated with deoxygenation of the pyranose ring. Both the location and degree of deoxygenation were evaluated by interrogating the energetic landscape for a number of mono- and dideoxyhexopyranose derivatives using DFT methods (M05-2X/cc-pVTZ(-f))...
December 12, 2018: Carbohydrate Research
Clifford Akateh, Eliza W Beal, Jung-Lye Kim, Brenda F Reader, Katelyn Maynard, Jay L Zweier, Bryan A Whitson, Sylvester M Black
BACKGROUND: Ischemia/reperfusion injury (IRI) can occur during liver surgery. Endogenous catalase is important to cellular antioxidant defenses and is critical to IRI prevention. Pegylation of catalase (PEG-CAT) improves its therapeutic potential by extending plasma half-life, but systemic administration of exogenous PEG-CAT has been only mildly therapeutic for hepatic IRI. Here, we investigated the protective effects of direct intrahepatic delivery of PEG-CAT during IRI using a rat hilar clamp model...
February 13, 2019: Journal of Surgical Research
Jing Chen, Xiaobei Liu, Yichen Xu, Kai Zhang, Jiayuan Huang, Banzhou Pan, Dongqin Chen, Shiyun Cui, Haizhu Song, Rui Wang, Xiaoyuan Chu, Xiaoli Zhu, Longbang Chen
Chemoresistance remains a great obstacle in effective lung adenocarcinoma (LUAD) treatment. Previously, we verified the role of microRNA-200b (miR-200b) in the formation of docetaxel (DTX)-resistant LUAD cells. This study aims to investigate the mechanism underlying the low level of miR-200b in DTX-resistant LUAD cells. The real-time reverse transcription (RT2 ) lncRNA PCR array system was applied to explore lncRNAs that potentially regulated miR-200b in DTX-resistant LUAD cells. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) contributed to the low miR-200b level in DTX-resistant LUAD cells...
January 18, 2019: Molecular Therapy. Nucleic Acids
Shipin Zhang, Kristeen Ye Wen Teo, Shang Jiunn Chuah, Ruenn Chai Lai, Sai Kiang Lim, Wei Seong Toh
The efficacy of mesenchymal stem cell (MSC) therapies is increasingly attributed to paracrine secretion, particularly exosomes. In this study, we investigated the role of MSC exosomes in the regulation of inflammatory response, nociceptive behaviour, and condylar cartilage and subchondral bone healing in an immunocompetent rat model of temporomandibular joint osteoarthritis (TMJ-OA). We observed that exosome-mediated repair of osteoarthritic TMJs was characterized by early suppression of pain and degeneration with reduced inflammation, followed by sustained proliferation and gradual improvements in matrix expression and subchondral bone architecture, leading to overall joint restoration and regeneration...
February 8, 2019: Biomaterials
Zhenhua Li, Yuping Liu, Xuejin Huang, Changming Hu, Hongwei Wang, Lin Yuan, John L Brash, Hong Chen
Gene transfection, as an effective treatment for inherited and acquired life threatening diseases caused by genetic deficiencies and abnormalities, has evolved as a promising therapeutic strategy for cancer and other intractable diseases. Non-target-specific vectors will affect normal cells as well as pathogenic cells, resulting in a relative decrease in transfection efficiency and unnecessary cytotoxicity. In the present work, gold nanoparticles (AuNPs) functionalized with folate (FA)-modified polyethylenimine (PEI-FA) were prepared by a single step method (without additional reducing agent) for targeted gene transfection in tumor cells...
February 6, 2019: Colloids and Surfaces. B, Biointerfaces
Hsin-Hung Chen, I-Lin Lu, Te-I Liu, Yuan-Chung Tsai, Wen-Hsuan Chiang, Sung-Chyr Lin, Hsin-Cheng Chiu
To overcome low therapeutic efficacy of chemotherapy against multidrug resistance (MDR) breast cancer, a combination therapy system based upon functionalized polymer nanoparticles comprising poly(γ-glutamic acid)-g-poly(lactic-co-glycolic acid) (γ-PGA-g-PLGA) as the major component was developed. The NPs were loaded with doxorubicin (DOX) and indocyanine green (ICG) for dual modality cancer treatment and coated with cholesterol-PEG (C-PEG) for MDR abrogation in treatment of human MDR breast cancer. The in vitro cellular uptake of the DOX/ICG loaded nanoparticles (DI-NPs) by MDR cancer cells was significantly enhanced owing to effective inhibition of the P-gp activity by C-PEG and γ-PGA receptor-mediated endocytosis...
February 5, 2019: Colloids and Surfaces. B, Biointerfaces
Ricardo Alonso, Edgar Carnero Contentti, Gaston Imhoff, Pablo A Lopez, Adrian Rubstein, Santiago Tizio
Current multiple sclerosis (MS) therapeutic options have significantly increased treatment algorithm complexity. This urges physicians to take into account multiple factors in the decision-making process and make an even more thorough analysis of the risk-benefit balance. We carried out a descriptive review aiming to assess some factors that endanger the proper MS treatment fulfillment, focusing mainly on Latin American countries. Firstly, it is paramount to warrant the correct, fair and timely treatment access...
February 7, 2019: Multiple Sclerosis and related Disorders
Rebecca M Wadey, Katherine D Connolly, Donna Mathew, Gareth Walters, D Aled Rees, Philip E James
BACKGROUND AND AIMS: Obesity is associated with an increased risk of cardiovascular disease, but the mechanisms involved are not completely understood. In obesity, the adipocyte microenvironment is characterised by both hypoxia and inflammation. Therefore, we sought to determine whether extracellular vesicles (EVs) derived from adipocytes in this setting might be involved in mediating cardiovascular disease, specifically by promoting leukocyte attachment to vascular endothelial cells...
January 24, 2019: Atherosclerosis
David G Leach, Simon Young, Jeffrey D Hartgerink
Macroscale biomaterials, such as preformed implantable scaffolds and injectable soft materials, possess powerful synergies with anti-cancer immunotherapies. Immunotherapies on their own typically have poor delivery properties, and often require repeated high-dose injections that result in serious off-tumor effects and/or limited efficacy. Rationally designed biomaterials allow for discrete localization and controlled release of immunotherapeutic agents, and have been shown in a large number of applications to improve outcomes in the treatment of cancers via immunotherapy...
February 13, 2019: Acta Biomaterialia
Wei-Hsun Hsu, Xiaoliang Zhao, Jianquan Zhu, In-Kyu Kim, Guanhua Rao, Justine McCutcheon, Shuo-Tse Hsu, Beverly Teicher, Bhaskar Kallakury, Afshin Dowlati, Yu-Wen Zhang, Giuseppe Giaccone
INTRODUCTION: Platinum-based chemotherapy remains the standard treatment for patients with small cell lung cancer (SCLC), but the benefit of the treatment is often hampered by rapid development of drug resistance. Thus far, there is no targeted therapy available for SCLC. Over 90% of SCLC tumors harbor mutations in the tumor suppressor gene p53, an important DNA damage checkpoint regulator, and these tumor cells rely predominantly on the checkpoint kinases to control DNA damage response...
February 13, 2019: Journal of Thoracic Oncology
Jong Woo Lee, Yu Zhang, Kyung Jin Eoh, Roshan Sharma, Miguel F Sanmamed, Jenny Wu, Justin Choi, Hee Sun Park, Akiko Iwasaki, Edward Kaftan, Lieping Chen, Vali Papadimitrakopoulou, Roy S Herbst, Ja Seok Koo
PURPOSE: To characterize the tumor-infiltrating immune cells population in Kras/p53-driven lung tumors and to evaluate the combinatorial anti-tumor effect with MEK inhibitor (MEKi), trametinib, and immunomodulatory monoclonal antibodies (mAbs) targeting either programmed cell death protein-1 (PD-1) or programmed cell death protein ligand 1 (PD-L1) in vivo. EXPERIMENTAL DESIGN: Trp53FloxFlox ;KrasG12D/+ ;Rosa26LSL-Luciferase/LSL-Luciferase (PKL) genetically engineered mice were utilized to develop autochthonous lung tumors with intratracheal delivery of adenoviral Cre recombinase...
February 13, 2019: Journal of Thoracic Oncology
Bárbara Paranhos Coelho, Mariana Maier Gaelzer, Fernanda Dos Santos Petry, Juliana Bender Hoppe, Vera Maria Treis Trindade, Christianne G Salbego, Fátima T C R Guma
Several studies have demonstrated the antitumor effect of doxazosin, an α1-adrenergic blocker, against glioma and breast, bladder and prostate cancers. Doxazosin is also being evaluated as a treatment for posttraumatic stress disorder and alcoholism, and α1-adrenergic blockers have been linked to neuroprotection in neurodegenerative disorders, such as Alzheimer's Disease (AD). Cancer and AD have an inverse relationship in many aspects, with several factors that contribute to apoptosis inhibition and proliferation being increased in cancers but decreased in AD...
February 13, 2019: Neuroscience
Mariana Oliveira Mendes, Alexandra Isabel Rosa, Andreia Neves Carvalho, Maria João Nunes, Pedro Dionísio, Elsa Rodrigues, Daniela Costa, Sara Duarte-Silva, Patrícia Maciel, Cecília Maria Pereira Rodrigues, Maria João Gama, Margarida Castro-Caldas
Parkinson's disease (PD) is a progressive neurological disorder, mainly characterized by the progressive loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc) and by the presence of intracellular inclusions, known as Lewy bodies. Despite SNpc being considered the primary affected region in PD, the neuropathological features are confined solely to the nigro-striatal axis. With disease progression other brain regions are also affected, namely the cerebral cortex, although the spreading of the neurologic damage to this region is still not completely unraveled...
February 13, 2019: Molecular and Cellular Neurosciences
Shruti Bakshi, Ann Depicker, Bert Schepens, Xavier Saelens, Paloma Juarez
With few exceptions, all currently marketed antibody therapeutics are IgG molecules. One of the reasons that other antibody isotypes are less developed are the difficulties associated with their purification. While commercial chromatography affinity resins like staphylococcal superantigen-like 7 (SSL7) protein containing resin, allow purification of IgAs from many animal species, these are not useful for murine IgAs. Because the mouse model is predominantly used for preclinical evaluation of IgA-based therapeutics, there is a need to develop an effective purification method for mouse IgA...
February 13, 2019: Journal of Biotechnology
Qin Wang, Lei Dai, Yuan Wang, Jie Deng, Yi Lin, Qingnan Wang, Chao Fang, Zida Ma, Huiling Wang, Gang Shi, Lin Cheng, Yi Liu, Shuang Chen, Junshu Li, Zhexu Dong, Xiaolan Su, Lie Yang, Shuang Zhang, Ming Jiang, Meijuan Huang, Yang Yang, Dechao Yu, Zongguang Zhou, Yuquan Wei, Hongxin Deng
SARI (suppressor of activator protein 1, regulated by IFN) functions as a tumour suppressor and is inactivated in various cancers. However, the mechanism underlying SARI inactivation in cancer remains elusive. In this study, we detected a high level of DNA methylation of the SARI promoter and an inverse correlation between SARI promoter methylation and expression in malignant tissues from patients with colon cancer. Furthermore, we found that the SARI promoter methylation status is a prognostic indicator for patients with colon cancer...
February 13, 2019: Cancer Letters
Kamal Ahmed, Alexey Koval, Jiabin Xu, Alexandre Bodmer, Vladimir L Katanaev
Wnt signaling is overactivated in triple-negative breast cancer (TNBC) and several other cancers, and its suppression emerges as an effective anticancer treatment. However, no drugs targeting the Wnt pathway exist on the market nor in advanced clinical trials. Here we provide a comprehensive body of preclinical evidence that an anti-leprotic drug clofazimine is effective against TNBC. Clofazimine specifically inhibits canonical Wnt signaling in a panel of TNBC cells in vitro. In several mouse xenograft models of TNBC, clofazimine efficiently suppresses tumor growth, correlating with in vivo inhibition of the Wnt pathway in the tumors...
February 13, 2019: Cancer Letters
Gayong Shim, Quoc-Viet Le, Juhan Suh, Sunhee Choi, Gunwoo Kim, Han-Gon Choi, Young Bong Kim, M B Macgregor, Yu-Kyoung Oh
The combination of imaging and anticancer therapy has recently emerged as a promising strategy. However, nonspecific imaging signals and distribution of anticancer drugs at normal tissues limit the specificity of the combination therapy. To overcome the challenges, we designed a system which can selectively visualize cancer tissues and initiate the subsequent action of therapeutic molecules in tumor microenvironment. Exploiting the overexpression of matrix metalloproteinase (MMP) in the tumor microenvironment, we designed a graphene oxide (GO)-based nanosheet system loaded with a pegylated MMP-cleavable imaging probe and an anticancer peptide shielded under the imaging probe...
February 13, 2019: Journal of Controlled Release: Official Journal of the Controlled Release Society
Xin-Yu Li, Jing Yan, Jia Sun, Chao Li, Jing-Yi Jiang, Jia-Mei Wang, Xiao-Na Meng, Jia-Jian Liang, Hua-Qin Wang
BAG3 is a member of the cochaperone BAG family and often highly expressed in various cancers. Recently, evidences show that BAG3 promotes stemness of human cancer cells. IFN-stimulated genes 15 (ISG15) is an ubiquitin-like molecule, which is covalently conjugated with substrates to form ISGylated proteins. Global screening BAG3 interacting partners demonstrated that ISG15 might be a potential binding partner. The current study revealed that BAG3 did not interact with ISG15, but positively regulated ISG15 expression in pancreatic ductal adenocarcinoma cancer (PDAC)...
February 13, 2019: Biochimica et biophysica acta. Molecular cell research
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