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https://www.readbyqxmd.com/read/28429672/the-molecular-mechanisms-of-thalidomide-teratogenicity-and-implications-for-modern-medicine
#1
J Knobloch, D Jungck, A Koch
Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and anti-angiogenic activities are considered in many other refractory diseases...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28428191/the-role-of-minimal-residual-disease-testing-in-myeloma-treatment-selection-and-drug-development-current-value-and-future-applications
#2
Kenneth C Anderson, Daniel Auclair, Gary J Kelloff, Caroline C Sigman, Herve Avet-Loiseau, Ann T Farrell, Nicole J Gormley, Shaji K Kumar, Ola Landgren, Nikhil C Munshi, Michele Cavo, Faith E Davies, Alessandra Di Bacco, Jennifer S Dickey, Steven I Gutman, Howard R Higley, Mohamad A Hussein, J Milburn Jessup, Ilan R Kirsch, Richard F Little, Robert D Loberg, Jens G Lohr, Lata Mukundan, James L Omel, Trevor J Pugh, Gregory H Reaman, Michael D Robbins, A Kate Sasser, Nancy Valente, Elena Zamagni
Treatment of myeloma has benefited from the introduction of more effective and better tolerated agents, improvements in supportive care, better understanding of disease biology, revision of diagnostic criteria, and new sensitive and specific tools for disease prognostication and management. Assessment of minimal residual disease (MRD) in response to therapy is one of these tools, as longer progression-free survival (PFS) is seen consistently among patients who have achieved MRD negativity. Current therapies lead to unprecedented frequency and depth of response, and next generation flow and sequencing methods to measure MRD in bone marrow are in use and being developed with sensitivities in the range of 10(-5)‒10(-6) cells...
April 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28428065/in-vivo-studies-investigating-biodistribution-of-nanoparticle-encapsulated-rhodamine-b-delivered-via-dissolving-microneedles
#3
Joakim Kennedy, Eneko Larrañeta, Maelíosa T C McCrudden, Cian M McCrudden, Aaron J Brady, Steven J Fallows, Helen O McCarthy, Adrien Kissenpfennig, Ryan F Donnelly
Nanoparticles (NPs) have undergone extensive investigation as drug delivery and targeting vehicles. NP delivery is often via the parenteral route, reliant on administration using hypodermic needles, which can be associated with patient compliance issues and safety concerns. In the recent past, the intradermal delivery of NPs, via novel dissolving microneedle (MN) arrays has garnered interest in the pharmaceutical community. However, published studies using this combinatorial approach have been limited, in that they have focussed on the use of in vitro and ex vivo models only...
April 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28424405/the-bruton-s-tyrosine-kinase-inhibitor-ibrutinib-exerts-immunomodulatory-effects-through-regulation-of-tumor-infiltrating-macrophages
#4
Lingyan Ping, Ning Ding, Yunfei Shi, Lixia Feng, Jiao Li, Yalu Liu, Yufu Lin, Cunzhen Shi, Xing Wang, Zhengying Pan, Yuqin Song, Jun Zhu
The Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has demonstrated promising efficacy in a variety of hematologic malignancies. However, the precise mechanism of action of the drug remains to be fully elucidated. Tumor-infiltrating macrophages presented in the tumor microenvironment have been shown to promote development and progression of B-cell lymphomas through crosstalk mediated by secreted cytokines and chemokines. Because Btk has been implicated in Toll-like receptor (TLR) signaling pathways that regulate macrophage activation and production of proinflammatory cytokines, we investigated the immunomodulatory effects of Btk inhibitor on macrophages...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423741/lenalidomide-and-the-risk-of-serious-infection-in-patients-with-multiple-myeloma-a-systematic-review-and-meta-analysis
#5
Li Ying, Tong YinHui, Zheng Yunliang, Haozhen Sun
The immunomodulatory drug lenalidomide is highly effective against newly diagnosed and relapsed/refractory multiple myeloma (MM), but serious and even fatal infections have been associated with its use. In this meta-analysis, we assessed the overall risk of infection to MM patients treated with lenalidomide. Eleven phase II or III clinical trials, comprising 3,210 subjects, were selected from the Embase, Pubmed, and Cochrane Library databases, from the Clinical Trial Registration website, and from meeting abstracts and virtual presentations at the American Society of Clinical Oncology...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421360/update-on-chemotherapy-induced-peripheral-neuropathy
#6
REVIEW
Comana Cioroiu, Louis H Weimer
PURPOSE OF REVIEW: The purpose of this study was to briefly discuss chemotherapy-induced peripheral neuropathy (CIPN) and detail the most important and most recent chemotherapeutic agents implicated. This review will examine neuropathy mechanisms, risk factors, and clinical patterns; novel and prospective drugs with similar effects that are less well known to neurologists are discussed. RECENT FINDINGS: CIPN is increasingly recognized for its clinical importance and effect on patient quality of life...
June 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28421121/availability-pharmaceutics-security-pharmacokinetics-and-pharmacological-activities-of-patchouli-alcohol
#7
REVIEW
Guanying Hu, Cheng Peng, Xiaofang Xie, Sanyin Zhang, Xiaoyu Cao
Patchouli alcohol (PA), a tricyclic sesquiterpene, is one of the critical bioactive ingredients and is mainly isolated from aerial part of Pogostemon cablin (known as guanghuoxiang in China) belonging to Labiatae. So far, PA has been widely applied in perfume industries. This review was written with the use of reliable information published between 1974 and 2016 from libraries and electronic researches including NCKI, PubMed, Reaxys, ACS, ScienceDirect, Springer, and Wiley-Blackwell, aiming at presenting comprehensive outline of security, pharmacokinetics, and bioactivities of PA and at further providing a potential guide in exploring the PA and its use in various medical fields...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28413134/the-in-vitro-mimic%C3%A2-platform-reflects-age-associated-changes-in-immunological-responses-after-influenza-vaccination
#8
Allison Dauner, Pankaj Agrawal, Jose Salvatico, Tenekua Tapia, Vipra Dhir, S Farzana Shaik, Donald R Drake, Anthony M Byers
Increasing research and development costs coupled with growing concerns over healthcare expenditures necessitate the generation of pre-clinical testing models better able to predict the efficacy of vaccines, drugs and biologics. An ideal system for evaluating vaccine immunogenicity will not only be reliable but also physiologically relevant, able to be influenced by immunomodulatory characteristics such as age or previous exposure to pathogens. We have previously described a fully autologous human cell-based MIMIC® (Modular IMmune In vitro Construct) platform which enables the evaluation of innate and adaptive immunity in vitro, including naïve and recall responses...
April 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28412218/evaluation-of-the-combined-use-of-metronomic-zoledronic-acid-and-coriolus-versicolor-in-intratibial-breast-cancer-mouse-model
#9
Chun-Hay Ko, Grace Gar-Lee Yue, Si Gao, Ke-Wang Luo, Wing-Sum Siu, Wai-Ting Shum, Hoi-Ting Shiu, Julia Kin-Ming Lee, Gang Li, Ping-Chung Leung, Andreas Evdokiou, Clara Bik-San Lau
ETHNOPHARMACOLOGICAL RELEVANCE: Coriolus versicolor (CV) is a mushroom traditionally used for strengthening the immune system and nowadays used as immunomodulatory adjuvant in anticancer therapy. Breast cancer usually metastasizes to the skeleton, interrupts the normal bone remodeling process and causes osteolytic bone lesions. The aims of the present study were to evaluate its herb-drug interaction with metronomic zoledronate in preventing cancer propagation, metastasis and bone destruction...
April 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28408401/synergistic-immunostimulatory-effects-and-therapeutic-benefit-of-combined-histone-deacetylase-and-bromodomain-inhibition-in-non-small-cell-lung-cancer
#10
Dennis Adeegbe, Yan Liu, Patrick H Lizotte, Yusuke Kamihara, Amir R Aref, Christina Almonte, Ruben Dries, Yuyang Li, Shengwu Liu, Xiaoen Wang, Tiquella Warner-Hatten, Jessica Castrillon, Guo-Cheng Yuan, Neermala Poudel-Neupane, Haikuo Zhang, Jennifer L Guerriero, Shiwei Han, Mark M Awad, David A Barbie, Jerome Ritz, Simon S Jones, Peter S Hammerman, James E Bradner, Steven N Quayle, Kwok-Kin Wong
Effective therapies for non-small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, with a focus on key cell subsets that are engaged in an immune response...
April 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28405503/genotoxic-stress-modulates-the-release-of-exosomes-from-multiple-myeloma-cells-capable-of-activating-nk-cell-cytokine-production-role-of-hsp70-tlr2-nf-kb-axis
#11
Elisabetta Vulpis, Francesca Cecere, Rosa Molfetta, Alessandra Soriani, Cinzia Fionda, Giovanna Peruzzi, Giulio Caracciolo, Sara Palchetti, Laura Masuelli, Lucilla Simonelli, Ugo D'Oro, Maria Pia Abruzzese, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rossella Paolini, Marco Cippitelli, Angela Santoni, Alessandra Zingoni
Exosomes are a class of nanovesicles formed and released through the late endosomal compartment and represent an important mode of intercellular communication. The ability of anticancer chemotherapy to enhance the immunogenic potential of malignant cells mainly relies on the establishment of the immunogenic cell death (ICD) and the release of damage-associated molecular patterns (DAMPs). Here, we investigated whether genotoxic stress could promote the release of exosomes from multiple myeloma (MM) cells and studied the immunomodulatory properties they exert on NK cells, a major component of the antitumor immune response playing a key role in the immunosurveillance of MM...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28403532/temozolomide-increases-mhc-i-expression-via-nf-%C3%AE%C2%BAb-signaling-in-glioma-stem-cells
#12
Dongyong Zhang, Bo Qiu, Yunjie Wang, Yanlei Guan, Luyang Zhang, Anhua Wu
Gliomas are the most common and primary tumors of the central nervous system in adults. Temozolomide (TMZ) is the main drug used to treat glioma, however, prognosis remains poor for most patients. Glioma stem cells (GSCs) are thought to enable glioma initiation and evasion from immune surveillance; their immunogenicity can be determined by expression of major histocompatibility complex (MHC)-I. The present study investigated the effect of TMZ on MHC-I expression in GSCs. Glioma spheres were cultured in serum-free medium containing epidermal growth factor, basic fibroblast growth factor, and B27; MHC-I expression was detected by immunocytochemistry, quantitative real-time PCR, and flow cytometry...
April 12, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28403036/commercial-probiotic-products-a-call-for-improved-quality-control-a-position-paper-by-the-espghan-working-group-for-probiotics-and-prebiotics
#13
Sanja Kolaček, Iva Hojsak, Roberto Berni Canani, Alfredo Guarino, Flavia Indrio, Rok Orel, Bruno Pot, Raanan Shamir, Hania Szajewska, Yvan Vandenplas, Johannes van Goudoever, Zvi Weizman
: Probiotics have been proposed for a number of indications ranging from the hypothetical long term immunomodulatory effects to proven benefits in the management of different clinical conditions.An increasing number of commercial products containing probiotics are available. In those products, irrespective if it is food, food supplement, medical food or drug, the probiotic microorganisms have to be present in a sufficient number by the end of the shelf-life, to pass through the gastrointestinal tract resisting acid and bile, to colonize the gut, and to retain functional properties required to obtain the suggested beneficial effect...
April 11, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28402951/characterization-of-a-secreted-macrophage-migration-inhibitory-factor-homologue-of-the-parasitic-nematode-haemonchus-contortus-acting-at-the-parasite-host-cell-interface
#14
Yujian Wang, MingMin Lu, Shuai Wang, Muhammad Ehsan, RuoFeng Yan, XiaoKai Song, LiXin Xu, XiangRui Li
Modulation and suppression of the immune response of the host by nematode parasites have been reported extensively and the migration inhibitory factor (MIF) is identified as one of the major immunomodulator. In the present study, we cloned and produced recombinant MIF protein from the small ruminant's nematode parasite Haemonchus contortus (rHCMIF-1), and investigated its immunomodulatory effects on goat monocyte. Enzymatic assays indicated that rHCMIF-1 possessed tautomerase activity. Immunohistochemical test demonstrated that the native HCMIF-1 protein was predominantly localized at the body surface and internal surface of the worm's gut...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396715/immunomodulatory-oligonucleotide-imt504-effects-on-mesenchymal-stem-cells-as-a-first-in-class-immunoprotective-immunoregenerative-therapy
#15
REVIEW
Jorge Zorzopulos, Steven M Opal, Andrés Hernando-Insúa, Juan M Rodriguez, Fernanda Elías, Juan Fló, Ricardo A López, Norma A Chasseing, Victoria A Lux-Lantos, Maria F Coronel, Raul Franco, Alejandro D Montaner, David L Horn
The immune responses of humans and animals to insults (i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged pro-inflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. Mesenchymal stem cell (MSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions...
March 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28395559/management-of-myelofibrosis-jak-inhibition-and-beyond
#16
Maximilian Stahl, Amer M Zeidan
Myelofibrosis (MF) is characterized by bone marrow fibrosis with subsequent extramedullary hematopoiesis and abnormal cytokine expression leading to splenomegaly, constitutional symptoms and cytopenias. The discovery of the JAK2 V617F mutation in the majority of MF patients has been followed by significant progress in drug development for MF. Areas covered: In this article, we review advances in the understanding of the underlying disease biology, prognostic assessment and therapeutic modalities for MF. We provide clinical trial evidence behind using the JAK2 inhibitor ruxolitinib, erythropoiesis stimulating agents, androgens, immunomodulatory drugs, interferon, cytoreductive drugs and hypomethylating agents in MF...
April 11, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28388253/lenalidomide-in-the-treatment-of-chronic-lymphocytic-leukemia
#17
Gilad Itchaki, Jennifer R Brown
Lenalidomide is an immunomodulatory drug (IMiD) with a unique mode of action (MOA) that may vary across disease-type. It is currently approved in multiple myeloma (MM), myelodysplastic syndrome (MDS) and mantle cell lymphoma (MCL), yet is also clinically active in a host of lymphoproliferative diseases, including chronic lymphocytic leukemia (CLL). Due to its protean effects on the immune system, lenalidomide may be particularly appealing in CLL, which is distinct in its ability to evade immune recognition and cause immunosuppression...
April 7, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28387444/comparative-modulation-of-levels-of-oxidative-stress-in-the-liver-of-anti-tuberculosis-drug-treated-wistar-rats-by-vitamin-b12-beta-carotene-and-spirulina-fusiformis-role-of-nf-kb-inos-il-6-and-il-10
#18
Sherry Joseph Martin, Evan Prince Sabina
PURPOSE: Isoniazid (INH) and Rifampicin (RIF) are known hepatotoxic agents. We compared the efficacy of Spirulina fusiformis and its active components vitamin B12 and beta-carotene in attenuating INH & RIF induced hepatotoxicity. We also tried to elucidate the inflammatory mechanism behind anti-tuberculosis drug induced hepatotoxicity. METHODS: INH & RIF were administered to Wistar albino rats for 28 days to induce hepatotoxicity. Spirulina fusiformis, vitamin B12 and beta-carotene were co-administered with INH & RIF and their hepatoprotective, antioxidant and immunomodulatory roles were studied through blood and liver analysis...
April 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28377922/mesenchymal-stem-cell-derived-exosomes-immunomodulatory-evaluation-in-an-antigen-induced-synovitis-porcine-model
#19
Javier G Casado, Rebeca Blázquez, Francisco Javier Vela, Verónica Álvarez, Raquel Tarazona, Francisco Miguel Sánchez-Margallo
Synovitis is an inflammatory process associated with pain, disability, and discomfort, which is usually treated with anti-inflammatory drugs or biological agents. Mesenchymal stem cells (MSCs) have been also successfully used in the treatment of inflammatory-related diseases such as synovitis or arthritis. In the last years, the exosomes derived from MSCs have become a promising tool for the treatment of inflammatory-related diseases and their therapeutic effect is thought to be mediated (at least in part) by their immunomodulatory potential...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28376403/treatment-with-adipose-derived-mesenchymal-stem-cells-and-their-conditioned-media-reverse-carrageenan-induced-paw-oedema-in-db-db-mice
#20
Nitya Shree, Sunil Venkategowda, M V Venkatranganna, Ramesh R Bhonde
Mesenchymal stem cells are known for anti inflammatory and immunomodulatory activities. The aim of our study was to evaluate the effect of human adipose derived mesenchymal stem cells (hADMSCs) and its conditioned media (CM) on carrageenan induced acute inflammation in db/db mice. We injected 5×10(5) ADMSCs or the CM in the inflamed paw. We assessed the paw volume, serum IL6 levels and histopathology of the paw to reveal the anti inflammatory effect. We observed a single injection of hADMSCs or CM could reverse the inflammation within 24h as evidenced by reduction in paw volume, IL6 levels and histological examination...
April 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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