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Immunomodulatory drugs

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https://www.readbyqxmd.com/read/28329729/prodrugs-of-triterpenoids-and-their-derivatives
#1
REVIEW
Meng Zhou, Rong-Hong Zhang, Min Wang, Guo-Bo Xu, Shang-Gao Liao
Triterpenoids are structurally diverse organic compounds that exist widely as natural products. Triterpenoids and their derivatives possess a wide range of biological effects including hepatoprotective, hypoglycemic, immunomodulatory, anti-inflammatory, anti-oxidant, and antitumor activities. In particular, the lupane-, oleanane-, and ursane-type triterpenes have been reported to exhibit pharmacological effects without prominent toxicity even at higher concentrations. Whereas, the poor drug-like properties (e...
March 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28326930/effects-of-jwh015-in-cytokine-secretion-in-primary-human-keratinocytes-and-fibroblasts-and-its-suitability-for-topical-transdermal-delivery
#2
Alicia Bort, Perla A Alvarado-Vazquez, Carolina Moracho-Vilrriales, Kristopher G Virga, Giuseppe Gumina, Alfonso Romero-Sandoval, Scott Asbill
Background JWH015 is a cannabinoid (CB) receptor type 2 agonist that produces immunomodulatory effects. Since skin cells play a key role in inflammatory conditions and tissue repair, we investigated the ability of JWH015 to promote an anti-inflammatory and pro-wound healing phenotype in human primary skin cells. Methods Human primary keratinocytes and fibroblasts were stimulated with lipopolysaccharide. The mRNA expression of cannabinoid receptors was determined using RT-PCR. The effects of JWH015 (0.05, 0...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28325256/how-have-evolutions-in-strategies-for-the-treatment-of-relapsed-refractory-multiple-myeloma-translated-into-improved-outcomes-for-patients
#3
REVIEW
Pieter Sonneveld, Edwin De Wit, Philippe Moreau
Although multiple myeloma (MM) remains incurable, the introduction of novel agents has improved clinical outcomes dramatically over the past 15 years. Response rates have risen from ∼30% with single agents to up to 90% with combination therapies. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, form the foundations for treatment of relapsed and/or refractory MM (RRMM). Newer agents, such as the IMiD pomalidomide, the histone deacetylase inhibitor panobinostat and the proteasome inhibitors carfilzomib and ixazomib, as well as the monoclonal antibodies daratumumab and elotuzumab, have further improved overall response rates in these patients...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28323051/anticancer-and-anti-angiogenic-activities-of-extract-from-actinidia-eriantha-benth-root
#4
Jian-Guo Wu, Li Ma, Shui-Hua Lin, Yan-Bin Wu, Jun Yi, Bin-Jun Yang, Jin-Zhong Wu, Ka-Hing Wong
ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Actinidia eriantha Benth (AER) are commonly used traditional folk medicine for the treatment of gastric carcinoma, nasopharyngeal carcinoma, and breast carcinoma. Besides, the anti-proliferative and immunomodulatory effects of AER polysaccharides on tumor-bearing mice have been reported previously. AIM OF THE STUDY: This work was carried out to investigate the anticancer and anti-angiogenic activities of AER. MATERIALS AND METHODS: The growth inhibitory effects of ethanol extracts from the leaves (EEL), stems (EES) and roots (EER) of A...
March 17, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28322750/supradural-inflammatory-soup-in-awake-and-freely-moving-rats-induces-facial-allodynia-that-is-blocked-by-putative-immune-modulators
#5
Julie Wieseler, Amanda Ellis, Andrew McFadden, Kendra Stone, Kimberley Brown, Sara Cady, Leandro F Bastos, David Sprunger, Niloofar Rezvani, Kirk Johnson, Kenner C Rice, Steven F Maier, Linda R Watkins
Facial allodynia is a migraine symptom that is generally considered to represent a pivotal point in migraine progression. Treatment before development of facial allodynia tends to be more successful than treatment afterwards. As such, understanding the underlying mechanisms of facial allodynia may lead to a better understanding of the mechanisms underlying migraine. Migraine facial allodynia is modeled by applying inflammatory soup (histamine, bradykinin, serotonin, prostaglandin E2) over the dura. Whether glial and/or immune activation contributes to such pain is unknown...
March 16, 2017: Brain Research
https://www.readbyqxmd.com/read/28320958/p97-vcp-promotes-degradation-of-crbn-substrate-glutamine-synthetase-and-neosubstrates
#6
Thang Van Nguyen, Jing Li, Chin-Chun Jean Lu, Jennifer L Mamrosh, Gang Lu, Brian E Cathers, Raymond J Deshaies
Glutamine synthetase (GS) plays an essential role in metabolism by catalyzing the synthesis of glutamine from glutamate and ammonia. Our recent study showed that CRBN, a direct protein target for the teratogenic and antitumor activities of immunomodulatory drugs such as thalidomide, lenalidomide, and pomalidomide, recognizes an acetyl degron of GS, resulting in ubiquitylation and degradation of GS in response to glutamine. Here, we report that valosin-containing protein (VCP)/p97 promotes the degradation of ubiquitylated GS, resulting in its accumulation in cells with compromised p97 function...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320145/vision-loss-in-tuberculous-meningitis
#7
REVIEW
Ravindra Kumar Garg, Hardeep Singh Malhotra, Neeraj Kumar, Ravi Uniyal
Vision loss is a disabling complication of tuberculous meningitis. Approximately, 15% of survivors are either completely or partially blind. All structures of the visual pathway may be affected in tuberculous meningitis. Optic nerve and optic chiasma are most frequently and dominantly affected. Thick-gelatinous exudates lying over the base of brain, are the pathological hallmark of tuberculous meningitis and are responsible for almost all of its major complications, including vision loss. Strangulation of optic nerves and optic chiasma by the exudates, compression over optic chiasma by the dilated third ventricle, raised intracranial pressure, endarteritis, shunt failure, bacterial invasion of optic nerves and drug-induced optic nerve damage are important reasons that are considered responsible for vision loss...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28317082/current-review-on-high-risk-multiple-myeloma
#8
REVIEW
Henry S H Chan, Christine I Chen, Donna E Reece
PURPOSE OF REVIEW: New risk stratification systems and treatment strategies have been introduced in recent years. We aim to provide an overview of these recent changes and summarise these data in a concise article that would be useful for clinicians. RECENT FINDINGS: Apart from clinical stage, disease genetics are now recognised as important prognostic risk factors, and various new cytogenetic changes with negative prognostic impact have been identified. New technologies such as minimal residual disease detection are also playing an important role in prognostic assessment...
March 20, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28316391/antileishmanial-and-immunomodulatory-potential-of-ocimumsanctum-linn-and-cocosnucifera-linn-in-murine-visceral-leishmaniasis
#9
Gaurav Bhalla, Sukhbir Kaur, Jaspreet Kaur, Rupinder Kaur, Puneet Raina
The role of immunomodulation in the therapeutic treatment of visceral leishmaniasis has gained eminence in view of moderate to severe drawbacks of the currently available drugs like toxicity, drug resistance and prohibitive costs. The potential for modulation of the immune system of many herbal plants can be tapped to address these problems. We conducted the present research study to investigate the antileishmanial and immunomodulatory effects of Ocimum sanctum Linn. and Cocos nucifera Linn. during the progression of visceral leishmaniasis in BALB/c mouse model...
March 2017: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
https://www.readbyqxmd.com/read/28306559/immunotherapy-a-new-treatment-paradigm-in-bladder-cancer
#10
Nicole N Davarpanah, Akira Yuno, Jane B Trepel, Andrea B Apolo
PURPOSE OF REVIEW: T-cell checkpoint blockade has become a dynamic immunotherapy for bladder cancer. In 2016, atezolizumab, an immune checkpoint inhibitor, became the first new drug approved in metastatic urothelial carcinoma (mUC) in over 30 years. In 2017, nivolumab was also approved for the same indication. This overview of checkpoint inhibitors in clinical trials focuses on novel immunotherapy combinations, predictive biomarkers including mutational load and neoantigen identification, and an evaluation of the future of bladder cancer immunotherapy...
March 16, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28303220/anemone-medicinal-plants-ethnopharmacology-phytochemistry-and-biology
#11
REVIEW
Da-Cheng Hao, Xiaojie Gu, Peigen Xiao
The Ranunculaceae genus Anemone (order Ranunculales), comprising more than 150 species, mostly herbs, has long been used in folk medicine and worldwide ethnomedicine. Various medicinal compounds have been found in Anemone plants, especially triterpenoid saponins, some of which have shown anti-cancer activities. Some Anemone compounds and extracts display immunomodulatory, anti-inflammatory, antioxidant, and antimicrobial activities. More than 50 species have ethnopharmacological uses, which provide clues for modern drug discovery...
March 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28302011/the-pharmacological-mechanisms-and-therapeutic-activities-of-hydroxychloroquine-in-rheumatic-and-related-diseases
#12
Changfeng Hu, Lu Lu, Jie-Ping Wan, Chengping Wen
Hydroxychloroquine (HCQ) is known as one of the most fascinating synthetic antimalarial drugs during the last 50 years. It is currently among the most commonly employed medicines for the clinical treatment of rheumatic diseases, especially systemic lupus erythematosus and rheumatoid arthritis. In related mechanism studies, it has been found that HCQ possesses various immunomodulatory and anti-inflammatory activities. In addition, the effects of HCQ on anti-platelet, metabolic pathways, and antineoplasticity have also been disclosed in more recent studies...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#13
Elena K Fetisova, Boris V Chernyak, Galina A Korshunova, Maria S Muntyan, Vladimir P Skulachev
BACKGROUND: Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28298557/chemical-approaches-to-targeted-protein-degradation-through-modulation-of-the-ubiquitin-proteasome-pathway
#14
REVIEW
Ian Collins, Hannah Wang, John J Caldwell, Raj Chopra
Manipulation of the ubiquitin-proteasome system to achieve targeted degradation of proteins within cells using chemical tools and drugs has the potential to transform pharmacological and therapeutic approaches in cancer and other diseases. An increased understanding of the molecular mechanism of thalidomide and its analogues following their clinical use has unlocked small-molecule modulation of the substrate specificity of the E3 ligase cereblon (CRBN), which in turn has resulted in the advancement of new immunomodulatory drugs (IMiDs) into the clinic...
March 15, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28291640/pegylated-interferon-alfa-2a-in-patients-with-essential-thrombocythaemia-or-polycythaemia-vera-a-post-hoc-median-83-month-follow-up-of-an-open-label-phase-2-trial
#15
Lucia Masarova, Keyur P Patel, Kate J Newberry, Jorge Cortes, Gautam Borthakur, Marina Konopleva, Zeev Estrov, Hagop Kantarjian, Srdan Verstovsek
BACKGROUND: Pegylated interferon alfa-2a is an immunomodulatory agent used to treat polycythemia vera. The durability of responses and long-term safety of this drug in patients with polycythaemia vera and essential thrombocythaemia have not been reported. Here, we present long-term efficacy and safety data from a single-centre, open-label, phase 2 trial, after a median of 83 months follow up. METHODS: Patients older than 18 years who were diagnosed with essential thrombocythaemia or polycythaemia vera according to 2001 WHO criteria were eligible to enrol in our study...
March 10, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28286787/topical-tacrolimus-in-anterior-segment-inflammatory-disorders
#16
REVIEW
Samir S Shoughy
Immune mediated inflammatory anterior segment diseases are variable and their management requires intense immunosuppression. Treatment with topical steroids is associated with serious ocular side effects. In order to overcome the potentially blinding complications of topical steroids, immunomodulatory drugs are being used more frequently. Tacrolimus is a calcineurin inhibitor that induces suppression of T lymphocytes activity and reduction of ocular inflammation. Tacrolimus was recently investigated for application in various anterior segment inflammatory disorders...
2017: Eye and Vision (London, England)
https://www.readbyqxmd.com/read/28285807/a-brighter-side-to-thalidomide-its-potential-use-in-immunological-disorders
#17
REVIEW
David Millrine, Tadamitsu Kishimoto
Thalidomide and its derivatives are immunomodulatory drugs (IMiDs) known for their sedative, teratogenic, anti-angiogenic, and anti-inflammatory properties. Commonly used in the treatment of cancers such as multiple myeloma and myelodysplastic syndrome (MDS), IMiDs have also been used in the treatment of an inflammatory skin pathology associated with Hansen's disease/leprosy. They have also shown promise in the treatment of autoimmune disorders including systemic lupus erythmatosus (SLE) and inflammatory bowel disease (IBD)...
March 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28285148/acute-variations-of-cytokine-levels-after-antipsychotic-treatment-in-drug-na%C3%A3-ve-subjects-with-a-first-episode-psychosis-a-meta-analysis
#18
REVIEW
Enrico Capuzzi, Francesco Bartoli, Cristina Crocamo, Massimo Clerici, Giuseppe Carrà
Schizophrenia is likely to be associated with immunological abnormalities. However, antipsychotics may induce immunomodulatory effects, by influencing plasma cytokines. In order to distinguish these influences, we carried out a systematic review and meta-analysis exploring the acute effect of antipsychotics on candidate cytokines plasma levels (IL-1β, IL-2, IL-6, IL-17, IFN-γ, TNF-α) among drug-naïve subjects with first episode psychosis. We searched main Electronic Databases, identifying eight studies meeting our inclusion criteria...
March 8, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28283653/antibody-drug-conjugates-bearing-pyrrolobenzodiazepine-or-tubulysin-payloads-are-immunomodulatory-and-synergize-with-multiple-immunotherapies
#19
Jonathan Rios-Doria, Jay Harper, Raymond Rothstein, Leslie Wetzel, Jon Chesebrough, Allison M Marrero, Cui Chen, Patrick Strout, Kathy Mulgrew, Kelly A McGlinchey, Ryan Fleming, Binyam Bezabeh, John Meekin, David Stewart, Maureen Kennedy, Philip Martin, Andrew Buchanan, Nazzareno Dimasi, Emil F Michelotti, Robert E Hollingsworth
Immunogenic cell death (ICD) is the process by which certain cytotoxic drugs induce apoptosis of tumor cells in a manner that stimulates the immune system. In this study, we investigated whether antibody-drug conjugates (ADC) conjugated with pyrrolobenzodiazepine dimer (PBD) or tubulysin payloads induce ICD, modulate the immune microenvironment, and could combine with IO drugs to enhance antitumor activity. We show that these payloads on their own induced an immune response that prevented the growth of tumors following subsequent tumor cell challenge...
March 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28277849/targeting-indolent-non-hodgkin-lymphoma
#20
Lori A Leslie, Alan P Skarbnik, Coleen Bejot, Susan Stives, Tatyana A Feldman, Andre H Goy
Due to recent advancements in the understanding of the molecular pathogenesis of B-cell malignancies, there has been an explosion of innovative agents in development. The purpose of this review is to efficiently summarize novel therapies with activity in indolent non-Hodgkin lymphoma (iNHL) targeting surface antigens, signaling pathways, and the tumor microenvironment. Areas covered: A literature search was performed to identify preclinical data and clinical trials focused on the use of targeted therapies in iNHL subtypes including follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia...
March 6, 2017: Expert Review of Hematology
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