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immunity therapy

Dongdong Guo, Xinyi Hu, Haojie Zhang, Chenghua Lu, Guangwei Cui, Xingjing Luo
Neuropathic pain affects patients worldwide. The therapeutic effects of current methods are still poor. This study was performed to investigate the neuro-protective effect of orientin in rats with spinal nerve ligation (SNL). In this study, the paw mechanical withdrawal threshold (PWT) and the paw thermal withdrawal latency (PWL) behavioral assays indicated that orientin alleviated the warm and mechanical allodynia in rats with SNL. The enzyme-linked immunosorbent assay (ELISA) showed that orientin suppressed the levels of pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor alpha (TNF-α) and increased the levels of anti-inflammatory cytokine interleukin-10 (IL-10)...
March 17, 2018: International Immunopharmacology
Hee Kyoung Kang, Moon-Chang Choi, Chang Ho Seo, Yoonkyung Park
Various organisms exist in the oceanic environment. These marine organisms provide an abundant source of potential medicines. Many marine peptides possess anticancer properties, some of which have been evaluated for treatment of human cancer in clinical trials. Marine anticancer peptides kill cancer cells through different mechanisms, such as apoptosis, disruption of the tubulin-microtubule balance, and inhibition of angiogenesis. Traditional chemotherapeutic agents have side effects and depress immune responses...
March 20, 2018: International Journal of Molecular Sciences
Honglin Jin, Chao Wan, Zhenwei Zou, Guifang Zhao, Lingling Zhang, Yuanyuan Geng, Tong Chen, Ai Huang, Fagang Jiang, Jue-Ping Feng, Jonathan F Lovell, Jing Chen, Gang Wu, Kunyu Yang
Immunosuppressive tumor microenvironments (TMEs) create tremendous obstacles for an effective cancer therapy. Herein, we developed a melittin-RADA32 hybrid peptide hydrogel loaded with doxorubicin (DOX) for a potent chemoimmunotherapy against melanoma through the active regulation of TMEs. The formed melittin-RADA32-DOX (MRD) hydrogel has an interweaving nanofiber structure and exhibits excellent biocompatibility, controlled drug release properties both in vitro and in vivo, and an enhanced killing effect to melanoma cells...
March 20, 2018: ACS Nano
Delia De Lisi, Ugo De Giorgi, Cristian Lolli, Giuseppe Schepisi, Vincenza Conteduca, Cecilia Menna, Giuseppe Tonini, Daniele Santini, Alberto Farolfi
To date, results of combination therapy studies have shown no meaningful clinical benefit over monotherapy and an unacceptably high degree of toxicity in the treatment of metastatic renal cell carcinoma (RCC), with the exception of a combination of immune-checkpoint inhibitors and the association of lenvatinib with everolimus. Lenvatinib is a potent multi-targeted tyrosine kinase inhibitor that targets VEGFR pathways. Everolimus inhibits primarily mTORC1 complex, a downstream effecter of the intracellular PI3K/AKT/mTOR pathway...
March 20, 2018: Expert Opinion on Drug Metabolism & Toxicology
James D Weinstein
Despite decades of research, at present there is no curative therapy for Alzheimer's disease. Changes in the way new drugs are tested appear to be necessary. Three changes are presented here and will be discussed. The first change is that Alzheimer's disease must be considered a disease of four major pathological processes, not one. The four processes are: 1) vascular hypoperfusion of the brain with associated mitochondrial dysfunction, 2) destructive protein inclusions, 3) uncontrolled oxidative stress, and 4) proinflammatory immune processes secondary to microglial and astrocytic dysfunction in the brain...
February 2018: Neural Regeneration Research
Sinem Civriz Bozdağ, Meltem Kurt Yüksel, Taner Demirer
Stem cells can be either totipotent, pluripotent, multipotent or unipotent. Totipotent cells have the capability to produce all cell types of the developing organism, including both embryonic and extraembryonic tissues. The Hematopoietic Stem Cells (HSC) are the first defined adult stem cells (ASC) that give rise to all blood cells and immune system. Use of HSCs for treatment of hematologic malignancies, which is also called bone marrow (BM) transplantation or peripheral blood stem cells (PBSC) transplantation is the pioneer of cellular therapy and translational research...
March 20, 2018: Advances in Experimental Medicine and Biology
Takeshi Yuasa, Shinji Urakami, Junji Yonese
Cytotoxic chemotherapy has been the mainstay of medical therapy for metastatic urothelial cancer. Currently, the gemcitabine/cisplatin regimen is widely used worldwide as the standard first-line medical treatment. Very recently, in 2017, pembrolizumab, a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1, was approved as a second-line treatment to be used after platina-based chemotherapy for metastatic urothelial cancer in Japan. Based on its promising anti-tumor efficacy and manageable safety profile as demonstrated in the phase III KEYNOTE-045 trial, pembrolizumab therapy is expected to be rapidly introduced for treating metastatic urothelial cancer in clinical practice...
March 20, 2018: International Journal of Clinical Oncology
Catherine A Lozupone
In recent years, there has been a deluge of papers linking altered microbiome compositions to a myriad of diseases. Mechanistic insight into microbial drivers of disease phenotypes is essential for translation to novel therapies. A key mechanism by which microbes influence health is immune modulation by components of their capsule and cell envelope and their metabolites. A major research focus of my laboratory is to gain mechanistic insight into which microbes modulate host immunity generally and in the context of disease...
March 2018: MSystems
Luminita Labusca, Florin Zugun-Eloae
Intra-articular adipose tissue deposits known as articular fat pads (AFPs) are described to exist within synovial joints. Their assumed role in normal joint biomechanics is increasingly objectivized by means of advanced methods of functional imaging. AFPs possess structural similarity with body subcutaneous white adipose tissue (WAT), however, seems to be regulated by independent metabolic loops. AFP dimension are conserved during extreme WAT states: obesity, metabolic syndrome, lipodystrophy, and cachexia...
2018: Frontiers in Veterinary Science
Lu Gan, Yanan Yang, Qian Li, Yi Feng, Tianshu Liu, Weijian Guo
Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a catalytic component of PRC2, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 also functions both as a transcriptional suppressor and a transcriptional co-activator, depending on H3K27me3 or not and on the different cellular contexts. Unsurprisingly, numerous studies have highlighted the role of EZH2 in cancer development and progression. Through modulating critical gene expression, EZH2 promotes cell survival, proliferation, epithelial to mesenchymal, invasion, and drug resistance of cancer cells...
2018: Biomarker Research
Chunhui Lai, Siliang Duan, Fang Ye, Xiaoqiong Hou, Xi Li, Jin Zhao, Xia Yu, Zixi Hu, Zhuoran Tang, Fengzhen Mo, Xiaomei Yang, Xiaoling Lu
PURPOSE: Dendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo. METHODS: We developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2180-188 peptide as liposomal vaccine...
2018: Theranostics
Yifan Wang, Weiye Deng, Nan Li, Shinya Neri, Amrish Sharma, Wen Jiang, Steven H Lin
Since the approval of anti-CTLA4 therapy (ipilimumab) for late-stage melanoma in 2011, the development of anticancer immunotherapy agents has thrived. The success of many immune-checkpoint inhibitors has drastically changed the landscape of cancer treatment. For some types of cancer, monotherapy for targeting immune checkpoint pathways has proven more effective than traditional therapies, and combining immunotherapy with current treatment strategies may yield even better outcomes. Numerous preclinical studies have suggested that combining immunotherapy with radiotherapy could be a promising strategy for synergistic enhancement of treatment efficacy...
2018: Frontiers in Pharmacology
Benjamin Benzon, Stephanie A Glavaris, Brian W Simons, Robert M Hughes, Kamyar Ghabili, Patrick Mullane, Rebecca Miller, Katriana Nugent, Brian Shinder, Jeffrey Tosoian, Ephraim J Fuchs, Phuoc T Tran, Paula J Hurley, Milena Vuica-Ross, Edward M Schaeffer, Charles G Drake, Ashley E Ross
BACKGROUND: Prostate cancer remains the second leading cause of cancer related death in men. Immune check point blocking antibodies have revolutionized treatment of multiple solid tumors, but results in prostate cancer remain marginal. Previous reports have suggested that local therapies, in particular cryoablation might increase tumor immunogenicity. In this work, we examine potential synergism between tumor cryoabalation and check point blocking antibodies. METHODS: FVB/NJ mice were injected subcutaneously into each flank with either 1 × 106 or 0...
March 20, 2018: Prostate Cancer and Prostatic Diseases
Yusheng Cheng, Hui Li, Yinan Deng, Yan Tai, Kaining Zeng, Yingcai Zhang, Wei Liu, Qi Zhang, Yang Yang
Emerging evidence indicate that cancer-associated fibroblasts (CAFs) affect tumor progression by reshaping the tumor microenvironment. Neutrophils are prominent components of solid tumors and important in cancer progression. Whether the phenotype and function of neutrophils in hepatocellular carcinoma (HCC) are influenced by CAFs is not well understood. Herein, we investigated the effect of HCC-derived CAFs (HCC-CAFs) on the neutrophils and explored the biological role of this effect. We found that HCC-CAFs induced chemotaxis of neutrophils and protected them from spontaneous apoptosis...
March 19, 2018: Cell Death & Disease
Marta A Toscano, Verónica C Martínez Allo, Anabela M Cutine, Gabriel A Rabinovich, Karina V Mariño
Although progress has been made in understanding the mechanisms implicated in the pathogenesis of autoimmune inflammation, studies aimed at identifying the mediators of these pathways will be necessary to develop more selective therapies. Galectins, a family of glycan-binding proteins, play central roles in immune cell homeostasis. Whereas some members of this family trigger regulatory programs that promote resolution of inflammation, others contribute to perpetuate autoimmune processes. We discuss the roles of endogenous galectins and their specific glycosylated ligands in shaping autoimmune responses by fueling, extinguishing, or rewiring immune circuits...
March 16, 2018: Trends in Molecular Medicine
Raja Muhammad Rashid, Zahid Nabi, Ahmad Zaki Ansari, Quratul-Ain Qaiser
BACKGROUND: Immune thrombocytopenic purpura (ITP) is primarily characterized by immune-mediated destruction of platelets in circulation. Major treatment options range from careful observation, steroids, immunosuppressive medications, immunoglobulins to splenectomy. Interestingly and rarely, ITP has also been reported after solid organ transplantation in patients receiving immunosuppressive medications. While the incidence of new onset ITP after solid organ transplant is comparatively well documented, new onset ITP after renal transplant has only been reported in two patients...
March 20, 2018: BMC Nephrology
Xue-Juan Bai, Hong-Min Li, You-Rong Yang, Jun-Xian Zhang, Yan Liang, Xue-Qiong Wu
Relapse of pulmonary tuberculosis (PTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis. Severe immunodeficiency or immune disorders may be the main reason for TB recurrence. This study aimed to quantify serum inflammatory cytokine and soluble adhesion molecule levels in Re-treated smear-positive PTB patients before and after re-anti-TB drug therapy. Serum samples were collected from 30 healthy controls and 215 Treated active PTB patients at baseline and 2, 4, and 6 months post-re-treatment...
March 16, 2018: Cytokine
Hoyoung Maeng, Masaki Terabe, Jay A Berzofsky
Therapeutic cancer vaccines have been a long-sought approach to harness the exquisite specificity of the immune system to treat cancer, but until recently have not had much success as single agents in clinical trials. However, new understanding of the immunoregulatory mechanisms exploited by cancers has allowed the development of approaches to potentiate the effect of vaccines by removing the brakes while the vaccines step on the accelerator. Thus, vaccines that had induced a strong T cell response but no clinical therapeutic effect may now reach their full potential...
March 16, 2018: Current Opinion in Immunology
Maria José Costa, Jyothirmayee Kudaravalli, Wen-Hui Liu, Jeffrey Stock, Sophanna Kong, Shu-Hui Liu
The development of therapeutic monoclonal antibodies through mouse immunization often originates drug candidates that are not cross-reactive to the mouse ortholog. In such cases, and particularly in oncology, drug efficacy studies are performed on human tumor xenografts or with "surrogate" anti-mouse ortholog antibodies if targeting tumor host cells. Safety assessment of drug candidate(s) is performed at a later development stage in healthy non-human primates. While the latter remains necessary before a drug advances into human subjects, it precludes evaluation of safety in disease conditions and drug de-risking during early development...
2018: PloS One
Vasudevan Bakthavatchalu, Katherine J Wert, Yan Feng, Anthony Mannion, Zhongming Ge, Alexis Garcia, Kathleen E Scott, Tyler J Caron, Carolyn M Madden, Johanne T Jacobsen, Gabriel Victora, Rudolf Jaenisch, James G Fox
Immune-compromised mouse models allow for testing the preclinical efficacy of human cell transplantations and gene therapy strategies before moving forward to clinical trials. However, CRISPR/Cas9 gene editing of the Wsh/Wsh mouse strain to create an immune-compromised model lacking function of Rag2 and Il2rγ led to unexpected morbidity and mortality. This warranted an investigation to ascertain the cause and predisposing factors associated with the outbreak. Postmortem examination was performed on 15 moribund mice...
2018: PloS One
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