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https://read.qxmd.com/read/30786171/drug-discovery-for-pemphigoid-diseases
#1
Anika Kasprick, Katja Bieber, Ralf J Ludwig
Pemphigoid diseases (PDs) are a group of autoimmune bullous diseases characterized and caused by autoantibodies targeting structural proteins of the skin and mucous membranes. Chronic inflammation, subepidermal blistering, and often scaring are the clinical characteristics of PDs. Itching and, in severe cases, disabilities resulting from scaring (i.e., blindness, esophageal strictures) are the leading subjective symptoms. Treatment of PDs, which is based on nonspecific immunosuppression, is challenging because of frequent relapses, lack of efficacy, and numerous adverse events...
February 20, 2019: Current Protocols in Pharmacology
https://read.qxmd.com/read/30785074/potential-mechanisms-of-action-related-to-the-efficacy-and-safety-of-cladribine
#2
REVIEW
David Baker, Gareth Pryce, Samuel S Herrod, Klaus Schmierer
Oral cladribine is a novel treatment for relapsing multiple sclerosis (MS). This appears to be a semi-selective immune-reconstitution therapy that induces long-term therapy from short treatment cycles. It has a relatively good safety profile that currently does not require extensive monitoring associated with some continuous immunosuppressive and relatively non-selective immune reconstitution therapies. The efficacy and safety of cladribine relates to its particular physicochemical properties, the function of the lymphocyte subsets that are selectively targeted by the drug and the repopulation kinetics of these subsets...
February 14, 2019: Multiple Sclerosis and related Disorders
https://read.qxmd.com/read/30784920/bone-marrow-mesenchymal-stem-cells-suppress-growth-and-promote-the-apoptosis-of-glioma-u251-cells-through-downregulation-of-the-pi3k-akt-signaling-pathway
#3
Li Lu, Guohu Chen, Jingjing Yang, Zhanjun Ma, Yang Yang, Yan Hu, Yubao Lu, Zhangqi Cao, Yan Wang, Xuexi Wang
Mesenchymal stem cells (MSCs), with the capacity for self-renewal and differentiation into multiple cell types, exhibit the property of homing towards tumor sites and immunosuppression and have been used as tumor-tropic vectors for tumor therapy. However, few studies have investigated the underlying molecular mechanisms that link MSCs to targeted tumor cells. In this study, we elucidated the inhibitory effects and mechanisms of human bone marrow mesenchymal stem cells (hBMSCs) on human glioma U251 cells using a co-culture system in vitro...
February 19, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://read.qxmd.com/read/30784054/egfr-targeted-therapy-alters-the-tumor-microenvironment-in-egfr-driven-lung-tumors-implications-for-combination-therapies
#4
Yijun Jia, Xuefei Li, Tao Jiang, Sha Zhao, Chao Zhao, Limin Zhang, Xiaozhen Liu, Jinpeng Shi, Meng Qiao, Jiawei Luo, Sangtian Liu, Ruoshuang Han, Chunxia Su, Shengxiang Ren, Caicun Zhou
Immune checkpoint inhibitors targeting the programmed cell death receptor/ligand 1 (PD-1/PD-L1) pathway have profoundly improved the clinical management of non-small-cell lung cancer (NSCLC). Nevertheless, the superiority of single-agent PD-1/PD-L1 inhibitors in pretreated EGFR mutant patients has turned out to be moderate. One proposed mechanism for poor response to immune checkpoint inhibitors is an immunosuppressive tumor microenvironment. Therefore, we utilized two autochthonous EGFR-driven lung tumor models to investigate dynamic microenvironmental responses to EGFR-TKI treatment...
February 5, 2019: International Journal of Cancer. Journal International du Cancer
https://read.qxmd.com/read/30783338/suspected-herpes-zoster-associated-encephalitis-during-treatment-with-oral-tofacitinib-in-alopecia-universalis
#5
Anna-Marie Hosking, Margit Juhász, Natasha Atanaskova Mesinkovska
Systemic administration of Janus kinase inhibitors (JAKis) is associated with adverse events, including serious infections, malignancy, and herpes zoster (HZ). Herein, we report a case of a 17-year-old male with alopecia universalis who developed suspected HZ-associated encephalitis (HZAE) during treatment with oral tofacitinib. Oral tofacitinib was immediately discontinued, and the patient was started on antiviral treatment. We present this case to highlight a serious complication that can arise with oral JAKi therapy...
November 2018: International Journal of Trichology
https://read.qxmd.com/read/30782662/targeting-mtor-with-mln0128-overcomes-rapamycin-and-chemoresistant-primary-effusion-lymphoma
#6
Carolina Caro-Vegas, Aubrey Bailey, Rachele Bigi, Blossom Damania, Dirk P Dittmer
Primary effusion lymphoma (PEL) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV). PEL has a highly active mTOR pathway, which makes mTOR a potential therapeutic target. MLN0128 is an ATP-competitive inhibitor of mTOR that has entered clinical trials for solid tumors. Our results demonstrated that MLN0128 has a greater effect on inhibiting proliferation than the allosteric mTOR inhibitor rapamycin. MLN0128 has ∼30 nM 50% inhibitory concentration (IC50 ) across several PEL cell lines, including PEL that is resistant to conventional chemotherapy...
February 19, 2019: MBio
https://read.qxmd.com/read/30781674/yifei-tongluo-a-chinese-herbal-formula-suppresses-tumor-growth-and-metastasis-and-exerts-immunomodulatory-effect-in-lewis-lung-carcinoma-mice
#7
Qiuchen Qi, Yanhong Hou, Ang Li, Yueyue Sun, Siying Li, Zhongxi Zhao
This study was aimed to investigate the anti-tumor, anti-metastasis and immunomodulatory effects of Yifei Tongluo (YFTL), a Chinese herbal formula, in Lewis lung carcinoma mice and to explore the underlying mechanisms. LLC cells were inoculated subcutaneously in C57BL/6 mice to establish the Lewis lung carcinoma model. We observed that YFTL effectively inhibited tumor growth and prolonged the overall survival of tumor-bearing mice. Additionally, YFTL treatment resulted in a significantly decreased number of surface lung metastatic lesions compared with the model control group...
February 18, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/30778878/italian-recommendations-for-the-diagnosis-and-treatment-of-myasthenia-gravis
#8
Amelia Evoli, Giovanni Antonini, Carlo Antozzi, Antonio DiMuzio, Francesco Habetswallner, Cesare Iani, Maurizio Inghilleri, Rocco Liguori, Renato Mantegazza, Roberto Massa, Elena Pegoraro, Roberta Ricciardi, Carmelo Rodolico
Myasthenia gravis is a well-treatable disease, in which a prompt diagnosis and an adequate management can achieve satisfactory control of symptoms in the great majority of patients. Improved knowledge of the disease pathogenesis has led to recognition of patient subgroups, according to associated antibodies, age at onset and thymus pathology, and to a more personalized treatment. When myasthenia gravis is suspected on clinical grounds, diagnostic confirmation relies mainly on the detection of specific antibodies...
February 18, 2019: Neurological Sciences
https://read.qxmd.com/read/30778826/steroid-therapy-in-children-with-iga-nephropathy
#9
REVIEW
Alexandra Cambier, Olivia Boyer, Georges Deschenes, James Gleeson, Anne Couderc, Julien Hogan, Thomas Robert
IgA nephropathy (IgAN) is one the most common primary glomerulonephritis in children and adolescents worldwide, with 20% of children developing end-stage kidney disease (ESKD) within 20 years of diagnosis. There is a need for treatment guidelines, especially for steroids in children with primary IgAN, since the STOP-IgA trial casts doubts on the use of steroids in adults with intermediate risk. Pediatricians are prone to prescribe steroids in addition to renin-angiotensin system blockade (RASB) when proteinuria is > 0...
February 18, 2019: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://read.qxmd.com/read/30778655/intravenous-human-immunoglobulin-and-or-methylprednisolone-pulse-therapies-as-a-possible-treat-to-target-strategy-in-immune-mediated-necrotizing-myopathies
#10
Jean Marcos de Souza, Leonardo Santos Hoff, Samuel Katsuyuki Shinjo
To evaluate the relevance of immunoglobulin (IVIg) and/or methylprednisolone pulse therapies in immune-mediated necrotizing myopathy (IMNM). Secondarily, to analyze the muscle damage measured by late magnetic resonance images (MRI). This retrospective study included 13 patients with defined IMNM (nine patients positive for the anti-signal recognition particle and four patients positive for hydroxyl-methyl-glutaryl coenzyme A reductase) who were followed from 2012 to 2018. International Myositis Assessment and Clinical Studies Group (IMACS) scoring assessed the response to a standardized treat-to-target protocol with disease activity core-set measures and late magnetic resonance imaging (MRI)...
February 18, 2019: Rheumatology International
https://read.qxmd.com/read/30778577/granulysin-and-granzyme-dependent-elimination-of-myeloid-cells-by-therapeutic-ova-specific-type-1-regulatory-t-cells
#11
Delphine Guipouy, Julie Gertner-Dardenne, Laurène Pfajfer, Yolla German, Nathalie Belmonte, Loïc Dupré
The intrinsic immunosuppressive properties of regulatory T (Treg) cells can be harnessed for therapeutic approaches aiming at down-modulating harmful immune reactions. In this context, expanded type 1 Treg cells (Tr1 cells) specific for ovalbumin (ova-Tr1 cells) have been tested for clinical efficacy in the treatment of autoimmune disorders such as refractory Crohn's disease (CD). The clinical use of these therapeutic products warrants exploration of their mechanism of action. Here, we identified a relationship between the CD activity index and the expression of lytic molecules by the ova-Tr1 cells administered in the previously reported First-in-Man study [Crohn's And Treg cells Study 1 (CATS1) study]...
February 19, 2019: International Immunology
https://read.qxmd.com/read/30778232/hypoimmunogenic-derivatives-of-induced-pluripotent-stem-cells-evade-immune-rejection-in-fully-immunocompetent-allogeneic-recipients
#12
Tobias Deuse, Xiaomeng Hu, Alessia Gravina, Dong Wang, Grigol Tediashvili, Chandrav De, William O Thayer, Angela Wahl, J Victor Garcia, Hermann Reichenspurner, Mark M Davis, Lewis L Lanier, Sonja Schrepfer
Autologous induced pluripotent stem cells (iPSCs) constitute an unlimited cell source for patient-specific cell-based organ repair strategies. However, their generation and subsequent differentiation into specific cells or tissues entail cell line-specific manufacturing challenges and form a lengthy process that precludes acute treatment modalities. These shortcomings could be overcome by using prefabricated allogeneic cell or tissue products, but the vigorous immune response against histo-incompatible cells has prevented the successful implementation of this approach...
February 18, 2019: Nature Biotechnology
https://read.qxmd.com/read/30777556/successful-management-of-late-onset-cytomegalovirus-induced-hemophagocytic-lymphohistiocytosis-in-kidney-transplant-recipient-after-coronary-artery-bypass-graft-surgery
#13
Torki Alotaibi, Mohamed Adel, Osama Gheith, Hasaneen Abo-Atya, Medhat A Halim, Prasad Nair, Tarek Mahmoud, Khaled Abdultawab, Medhat Fouad, Mohamed Mejahed, Sheikha Al-Mohareb
Hemophagocytic syndrome combines febrile hepatosplenomegaly, pancytopenia, hypofibrinemia, and hepatic dysfunction. It is characterized by bone marrow and organ infiltration of activated, nonmalignant macrophages that phagocytize blood cells. It is rare among renal transplant recipients. Here, we present the successful management of late-onset cytomegalovirusinduced hemophagocytic lymphohistiocytosis in a kidney transplant recipient after coronary artery bypass graft surgery. In 2012, our patient had end-stage kidney disease due to diabetic nephropathy and underwent related living-donor renal transplant...
January 2019: Experimental and Clinical Transplantation
https://read.qxmd.com/read/30777550/successful-treatment-with-abatacept-in-recurrent-focal-segmental-glomerulosclerosis-after-kidney-transplant
#14
Yaser Shah, Khalid Almeshari, Hassan Aleid, Dieter Broering, Ibrahim Alahmadi, Tariq Ali
Primary focal segmental glomerulosclerosis recurrence occurs in 10% to 50% of recipients after kidney transplant and may affect both children and adults. Treatment after recurrence with plasma exchange and immunosuppression is quite variable and challenging, and those who do not respond usually progress to allograft failure. Podocyte injury and B7-1 expression and subsequently its blockade (abatacept) have been reported to be associated with complete remission of proteinuria in 4 patients with focal segmental glomerulosclerosis recurrence after kidney transplantation and in 1 patient with focal segmental glomerulosclerosis in native kidney...
January 2019: Experimental and Clinical Transplantation
https://read.qxmd.com/read/30777534/management-of-chronic-active-antibody-mediated-rejection-in-renal-transplant-recipients-single-center-experience
#15
Prasad Nair, Osama Gheith, Torki Al-Otaibi, Mohamed Mostafa, Suzann Rida, Islam Sobhy, Medhat A Halim, Tarek Mahmoud, Mohamed Abdul-Hameed, Ayman Maher, Mohamed Emam
OBJECTIVES: Data on the management of chronic antibody-mediated rejection after kidney transplantation are limited. We aimed to assess the impact of treatment of biopsy-proven chronic active antibodymediated rejection with combined plasma exchange, intravenous immunoglobulin, and rituximab treatment versus intravenous immunoglobulin alone or conservative management on the evolution of renal function in renal transplant recipients. MATERIALS AND METHODS: In this retrospective study, we compared patients diagnosed with chronic active antibody-mediated rejection who were treated with standard of care steroids, intravenous immunoglobulin, plasma exchange, and rituximab (n = 40) at our center versus those who received intravenous immunoglobulin only or just intensified maintenance immunosuppression (n = 28)...
January 2019: Experimental and Clinical Transplantation
https://read.qxmd.com/read/30777532/efficacy-of-2-doses-of-rituximab-on-b-cell-and-antidonor-antibody-and-outcomes-of-abo-incompatible-living-donor-pediatric-kidney-transplant
#16
Yuko Hamasaki, Atsushi Aikawa, Yoshihiro Itabashi, Masaki Muramatsu, Yoji Hyoudou, Kazunobu Shinoda, Yusuke Takahashi, Kei Sakurabayashi, Toshihide Mizutani, Hideyo Oguchi, Takeshi Kawamura, Ken Sakai, Seiichiro Shishido
OBJECTIVES: Rituximab treatment strategies vary in ABOincompatible pediatric kidney transplant recipients. Here, we present the efficacy of 2 doses of rituximab and subsequent outcomes in ABO-incompatible pediatric kidney transplant patients. MATERIALS AND METHODS: Our study of ABO-incompatible pediatric kidney transplant recipients included 21 who were pretreated with desensitization that included 2 doses of 100 mg rituximab (rituximab group) at 10 and 1 day pretransplant and 14 who received splenectomy without rituximab (splenectomy group)...
January 2019: Experimental and Clinical Transplantation
https://read.qxmd.com/read/30777529/screening-for-bk-viremia-viruria-and-the-impact-of-management-of-bk-virus-nephropathy-in-renal-transplant-recipients
#17
Zakaria E Zakaria, Amir M Elokely, Adel A Ghorab, Adel I Bakr, Medhat A Halim, Osama A Gheith, Ayman M Nagib, Yahya Makkeyah, Mohamed A Balaha, Mahmoud M Magdy, Torki Al-Otaibi
OBJECTIVES: The prevalence of BK-induced nephritis in renal transplant recipients is estimated to be 1% to 10%; the rate of graft loss within 1 year is 30% to 65%. We conducted this study to evaluate screening of BK virus in blood and/or urine among renal transplant recipients and to assess the effects of different therapeutic modalities in renal transplant recipients with BK nephropathy. MATERIALS AND METHODS: Kidney transplant recipients were screened at the time of transplant and then at 1, 2, 3, 6, 9, 12, 18, and 24 months posttransplant...
January 2019: Experimental and Clinical Transplantation
https://read.qxmd.com/read/30777100/challenges-and-potential-of-pd-1-pd-l1-checkpoint-blockade-immunotherapy-for-glioblastoma
#18
REVIEW
Xin Wang, Gaochao Guo, Hui Guan, Yang Yu, Jie Lu, Jinming Yu
PD-1/PD-L1 checkpoint blockades have achieved significant progress in several kinds of tumours. Pembrolizumab, which targets PD-1, has been approved as a first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with positive PD-L1 expression. However, PD-1/PD-L1 checkpoint blockades have not achieved breakthroughs in treating glioblastoma because glioblastoma has a low immunogenic response and an immunosuppressive microenvironment caused by the precise crosstalk between cytokines and immune cells...
February 18, 2019: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/30777097/pediatric-anti-nmda-receptor-encephalitis-with-catatonia-treatment-with-electroconvulsive-therapy
#19
Taha Moussa, Khalid Afzal, Joseph Cooper, Ryan Rosenberger, Karyn Gerstle, Linda Wagner-Weiner
BACKGROUND: Anti-NMDA receptor encephalitis, an autoimmune disease associated with antibodies against N-methyl-D-aspartate (NMDA) receptors, is being diagnosed more frequently, especially in children and young adults. Acute neurological and psychiatric manifestations are the common presenting symptoms. Diagnosing anti-NMDA receptor encephalitis is often challenging given the wide range of clinical presentation, and may be further complicated by its overlap of symptoms, brain MRI changes, and CSF findings with other entities affecting the brain...
February 18, 2019: Pediatric Rheumatology Online Journal
https://read.qxmd.com/read/30776644/cyclosporin-a-inhibits-differentiation-and-activation-of-monocytic-cells-induced-by-27-hydroxycholesterol
#20
Yonghae Son, Jeongyoon Choi, Boyoung Kim, Young Chul Park, Seong-Kug Eo, Hyok-Rae Cho, Sun Sik Bae, Chi Dae Kim, Koanhoi Kim
27-Hydroxycholesterol (27OHChol) is a bioactive molecule that induces monocytic cell activation and differentiation and thereby participates in immune responses under hypercholesterolemic condition. However, it is unknown whether cyclosporin A (CsA), an immunosuppressant, affects biological effects of 27OHChol. In this study, we investigated whether CsA alters 27OHChol-induced cellular and molecular responses using the human monocyte/macrophage THP-1 cells. Treatment of the cells with CsA resulted in decreased expression of the mDC-specific markers (CD80, CD83 and CD88) induced by 27OHChol...
February 15, 2019: International Immunopharmacology
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