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Immunomodulatory therapy

Lindsay A Sceats, Arden M Morris, M Kate Bundorf, K T Park, Cindy Kin
BACKGROUND: Sex-based treatment disparities occur in many diseases. Women undergo fewer procedural interventions, and their care is less consistent with guideline-based therapy. There is limited research exploring sex-based differences in ulcerative colitis treatment. We hypothesized that women are less likely to be treated with strategies consistent with long-term disease remission, including surgery and maintenance medications. OBJECTIVE: The aim of this study was to determine if patient sex is associated with choice of treatment strategy for ulcerative colitis...
February 8, 2019: Diseases of the Colon and Rectum
Nan Zhou, Alvaro Gutierrez-Uzquiza, Xiang Yu Zheng, Renxu Chang, Dan T Vogl, Alfred L Garfall, Luca Bernabei, Anita Saraf, Laurence Florens, Michael P Washburn, Anuradha Illendula, John H Bushweller, Luca Busino
Ikaros family zinc finger protein 1 and 3 (IKZF1 and IKZF3) are transcription factors that promote multiple myeloma (MM) proliferation. The immunomodulatory imide drug (IMiD) lenalidomide promotes myeloma cell death via Cereblon (CRBN)-dependent ubiquitylation and proteasome-dependent degradation of IKZF1 and IKZF3. Although IMiDs have been used as first-line drugs for MM, the overall survival of refractory MM patients remains poor and demands the identification of novel agents to potentiate the therapeutic effect of IMiDs...
February 13, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Laura Saldaña, Fátima Bensiamar, Gema Vallés, Francisco J Mancebo, Eduardo García-Rey, Nuria Vilaboa
BACKGROUND: Immunoregulatory capacity of mesenchymal stem cells (MSC) is triggered by the inflammatory environment, which changes during tissue repair. Macrophages are essential in mediating the inflammatory response after injury and can adopt a range of functional phenotypes, exhibiting pro-inflammatory and anti-inflammatory activities. An accurate characterization of MSC activation by the inflammatory milieu is needed for improving the efficacy of regenerative therapies. In this work, we investigated the immunomodulatory functions of MSC primed with factors secreted from macrophages polarized toward a pro-inflammatory or an anti-inflammatory phenotype...
February 13, 2019: Stem Cell Research & Therapy
Zebin Wang, Kaiming Sun, Yonghong Xiao, Bin Feng, Keith Mikule, XiaoYan Ma, Ningping Feng, Christopher P Vellano, Lorenzo Federico, Joseph R Marszalek, Gordon B Mills, Jeffrey Hanke, Sridhar Ramaswamy, Jing Wang
PARP inhibitors have been proven clinically efficacious in platinum-responsive ovarian cancer regardless of BRCA1/2 status and in breast cancers with germline BRCA1/2 mutation. However, resistance to PARP inhibitors may preexist or evolve during treatment in many cancer types and may be overcome by combining PARP inhibitors with other therapies, such as immune checkpoint inhibitors, which confer durable responses and are rapidly becoming the standard of care for multiple tumor types. This study investigated the therapeutic potential of combining niraparib, a highly selective PARP1/2 inhibitor, with anti-PD-1 immune checkpoint inhibitors in preclinical tumor models...
February 12, 2019: Scientific Reports
Tina Gruosso, Mathieu Gigoux, Venkata Satya Kumar Manem, Nicholas Bertos, Dongmei Zuo, Irina Perlitch, Sadiq Mehdi Ismail Saleh, Hong Zhao, Margarita Souleimanova, Radia Marie Johnson, Anne Monette, Valentina Munoz Ramos, Michael Trevor Hallett, John Stagg, Réjean Lapointe, Atilla Omeroglu, Sarkis Meterissian, Laurence Buisseret, Gert Van den Eynden, Roberto Salgado, Marie-Christine Guiot, Benjamin Haibe-Kains, Morag Park
Understanding the tumor immune microenvironment (TIME) promises to be key for optimal cancer therapy, especially in triple-negative breast cancer (TNBC). Integrating spatial resolution of immune cells with laser capture microdissection gene expression profiles, we defined distinct TIME stratification in TNBC with implications for current therapies, including immune checkpoint blockade. TNBCs with an immunoreactive microenvironment exhibited tumoral infiltration of granzyme B+ CD8+ T cells, a type I interferon signature, elevated expression of multiple immune inhibitory molecules, including IDO, PD-L1, and good outcome...
February 12, 2019: Journal of Clinical Investigation
Jean-Louis Vincent, Wasineenart Mongkolpun
Sepsis, defined as infection plus some degree of organ dysfunction, is still associated with high mortality and morbidity rates. Management focuses on three key areas: infection control, hemodynamic stabilization and organ support, and modulation of the sepsis response. Areas covered: This review will not cover infection control. Hemodynamic stabilization essentially involves use of adequate fluid resuscitation and vasopressors. Fluid and vasopressor choices and targets are discussed, and the need to adapt these to the individual patient is stressed...
February 12, 2019: Expert Review of Anti-infective Therapy
Hao Nguyen Trong, Thang Nguyen Tat, Tu Tran Nguyen Anh, Nhi Pham Uyen, Thuong Nguyen Van, Khang Tran Hau, Marco Gandolfi, Francesca Satolli, Claudio Feliciani, Michael Tirant, Aleksandra Vojvodic, Torello Lotti
BACKGROUND: Psoriasis, the prevalence of which ranges from 2% to 3% of the general population, has been recently recognised as not only a chronic inflammatory skin disorder but also an immunometabolic systemic disease. Dyslipidemia is one of the most important comorbidities of psoriasis. Statins, frequently used as anti-hyperlipidemic agents, may be beneficial in the treatment of several autoimmune diseases, including psoriasis, due to their anti-inflammatory and immunomodulatory characteristics...
January 30, 2019: Open Access Macedonian Journal of Medical Sciences
Sukeshani Salwe, Amitkumar Singh, Varsha Padwal, Shilpa Velhal, Vidya Nagar, Priya Patil, Alaka Deshpande, Vainav Patel
BACKGROUND: HIV-2 infection is characterised by a longer asymptomatic phase and slower AIDS progression than HIV-1 infection. Identifying unique immune signatures associated with HIV-2 pathogenesis may thus provide therapeutically useful insight into the management of HIV infection. This study examined the dynamics of the CD4+ T cell compartment, critical in disease progression, focussing on chronic HIV-2 and HIV-1 infected individuals at various stages of disease progression. METHODS: A total of 111 participants including untreated and treated HIV infected individuals and seronegative individuals were enrolled in this study...
February 11, 2019: BMC Infectious Diseases
Elia Bari, Sara Perteghella, Laura Catenacci, Marzio Sorlini, Stefania Croce, Melissa Mantelli, Maria A Avanzini, Milena Sorrenti, Maria L Torre
AIM: To validate the use of ultrafiltration (UF) as an alternative applicable industrial method to replace ultracentrifugation (UC) in the purification of mesenchymal stromal cell (MSC)-secretome. MATERIALS & METHODS: Pharmaceutical formulations containing secretome and/or extracellular vesicles were extracted from adipose-MSCs and bone marrow-MSCs by combining UF or UC with lyophilization. RESULTS & CONCLUSION: UF led to higher protein, lipid, cytokine and exosomes yields compared with UC...
February 11, 2019: Nanomedicine
Mitsuhiro Ebara
The field of biomaterials has seen a strong rejuvenation due to the new potential to modulate immune system in our body. This special class of materials is called "immunomodulatory biomaterials". Generally, three fundamental strategies are followed in the design of immunomodulatory biomaterials: (1) immuno-inert biomaterials, (2) immuno-activating biomaterials, and (3) immuno-tolerant biomaterials. While many applications of immuno-inert biomaterials such as biocompatible medical implants have been already proposed in the past decades, the ability to engineer biological activity into synthetic materials greatly increases the number of their potential uses and improves their performance in more traditional applications...
January 2019: Chonnam Medical Journal
Eduardo F Mufarrege, Lydia A Haile, Marina Etcheverrigaray, Daniela I Verthelyi
Recombinant human interferon-β (rhIFN-β) therapy is the first-line treatment in relapsing-remitting forms of multiple sclerosis (MS). The mechanism of action underlying its therapeutic activity is only partially understood as IFN-βs induce the expression of over 1000 genes modifying multiple immune pathways. Currently, assessment of potency for IFN-β products is based on their antiviral effect, which is not linked to its therapeutic effect. Here, we explore the use of a multiplexed gene expression system to more broadly characterize IFN-β bioactivity...
February 8, 2019: AAPS Journal
Xiao-Tao He, Xuan Li, Yu Xia, Yuan Yin, Rui-Xin Wu, Hai-Hua Sun, Fa-Ming Chen
Recently, we found that although high-stiffness matrices stimulated osteogenic differentiation of bone marrow-derived stromal cells (BMSCs), the macrophages (Mφs) in high-stiffness transglutaminase crosslinked gelatins (TG-gels) tended to undergo M1 polarization and hence compromised cell osteogenesis. In this study, we hypothesized that the copresentation of interleukin (IL)-4 and stromal cell-derived factor (SDF)-1α in high-stiffness TG-gels may enhance periodontal regeneration by modulating Mφ polarization and promoting endogenous stem cell recruitment...
February 5, 2019: Acta Biomaterialia
Jelena Pantic, Laure Guilhaudis, Vishal Musale, Samir Attoub, Miodrag L Lukic, Milena Mechkarska, J Michael Conlon
The aim of the study was to determine the in vitro immunomodulatory, cytotoxic, and insulin-releasing activities of seven phylloseptin-TR peptides and plasticin-TR, first isolated from the frog Phyllomedusa trinitatis. The most cationic peptides, phylloseptin-1.1TR and phylloseptin-3.1TR, showed greatest cytotoxic potency against A549, MDA-MB231, and HT-29 human tumor-derived cells and against mouse erythrocytes. Phylloseptin-4TR was the most hydrophobic and the most effective peptide at inhibiting production of the proinflammatory cytokines TNF-α and IL-1β by mouse peritoneal cells but was without effect on production of the antiinflammatory cytokine IL-10...
February 7, 2019: Journal of Peptide Science: An Official Publication of the European Peptide Society
Abdullah Ladha, Jianzhi Zhao, Elliot M Epner, Jeffrey J Pu
Mantle cell lymphoma is a relatively new recognized hematological malignant disease, comprising of 2.5-6% non-Hodgkin's lymphomas. The complexity of its clinical presentations (nodular pattern, diffuse pattern, and blastoid variant), variety in disease progression, and treatment response, make this disease a research focus to both experimental oncology and clinical oncology. Overexpression of cyclin D1 and chromosome t(11,14) translocation are the known molecular biomarkers of this disease. Mantle cell international prognostic index (MIPI), ki-67 proliferation index, and TP53 mutation are emerging as the prognostic biomarkers...
2019: Experimental Hematology & Oncology
Boris M Baranovski, Ronen Schuster, Omer Nisim, Ido Brami, Yotam Lior, Eli C Lewis
Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder which most commonly manifests as pulmonary emphysema. Accordingly, alpha-1 antitrypsin (AAT) augmentation therapy aims to reduce the progression of emphysema, as achieved by life-long weekly slow-drip infusions of plasma-derived affinity-purified human AAT. However, not all AATD patients will receive this therapy, due to either lack of medical coverage or low patient compliance. To circumvent these limitations, attempts are being made to develop lung-directed therapies, including inhaled AAT and locally-delivered AAT gene therapy...
September 19, 2018: Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation
Sergio M Pontejo, Carolina Sanchez, Begoña Ruiz-Argüello, Antonio Alcami
Etanercept is a soluble form of the tumor necrosis factor receptor 2 (TNFR2) that inhibits pathological tumor necrosis factor (TNF) responses in rheumatoid arthritis and other inflammatory diseases. However, besides TNF, etanercept blocks also lymphotoxin-α (LTα), which has no clear therapeutical value and might aggravate some of the adverse effects associated with etanercept. Poxviruses encode soluble TNFR2 homologs, termed viral TNF decoy receptors (vTNFRs), that display unique specificity properties. For instance, cytokine response modifier D (CrmD) inhibits mouse and human TNF and mouse LTα, but it is inactive against human LTα...
February 5, 2019: Journal of Biological Chemistry
Connie S Chamberlain, Anna B Clements, John A Kink, Ugeun Choi, Geoffrey S Baer, Matthew A Halanski, Peiman Hematti, Ray Vanderby
Tendon healing follows a complex series of coordinated events that ultimately produces a mechanically inferior tissue more scar-like than native tendon. More regenerative healing occurs when anti-inflammatory M2 macrophages play a more dominant role. Mesenchymal stromal/stem cells (MSCs) are able to polarize macrophages to an M2 immunophenotype via paracrine mechanisms. We previously reported that co-culture of CD14+ macrophages (MQs) with MSCs resulted in a unique M2-like macrophage. More recently, we generated M2-like macrophages using only extracellular vesicles (EVs) isolated from MSCs creating "EV-educated macrophages" (also called exosome-educated macrophages, EEMs), thereby foregoing direct use of MSCs...
February 5, 2019: Stem Cells
Rieke Alten, P G Conaghan, V Strand, E Sullivan, S Blackburn, H Tian, K Gandhi, S M Jugl, A Deodhar
OBJECTIVE: There are limited data on therapy selection and switching in psoriatic arthritis (PsA). This 18 country, real-world study assessed use and switching of immunomodulatory therapy (biologic/apremilast), the extent of treatment failure and its association with reduced physical functioning, health-related quality of life (HRQoL), and work productivity and activity impairment (WPAI). METHODS: PsA patients under routine care and their treating physicians provided demographics, current therapy, reasons for switching, duration of first therapy, HRQoL, HAQ-DI, and WPAI...
February 4, 2019: Clinical Rheumatology
Laurens E Franssen, Tuna Mutis, Henk M Lokhorst, Niels W C J van de Donk
The treatment of multiple myeloma (MM) has evolved substantially over the past decades, leading to a significantly improved outcome of MM patients. The introduction of high-dose therapy, especially, and autologous stem cell transplantation, as well as the development of new drugs, such as immunomodulatory drugs (IMiDs) and proteasome inhibitors have contributed to the improvement in survival. However, eventually most MM patients relapse, which indicates that there is a need for new agents and novel treatment strategies...
2019: Therapeutic Advances in Hematology
Grerk Sutamtewagul, Brian K Link
Follicular lymphoma (FL) is a common B-cell malignancy characterized by relatively indolent growth and incurability with an expected lifetime course of serial intermittent treatment courses. Many patients with FL have lives shortened by the disease and despite a relatively favorable prognosis relative to other incurable systemic malignancies, optimal management of FL has not been achieved. This review focuses on identifying both patients for whom novel therapies might be most beneficial as well as systematically reviewing novel strategies at various levels of investigation...
2019: Therapeutic Advances in Hematology
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