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HIV infection in the elderly.

In the US, an estimated 1 million people are infected with HIV, although one-third of this population are unaware of their diagnosis. While HIV infection is commonly thought to affect younger adults, there are an increasing number of patients over 50 years of age living with the condition. UNAIDS and WHO estimate that of the 40 million people living with HIV/AIDS in the world, approximately 2.8 million are 50 years and older. With the introduction of highly active antiretroviral therapy (HAART) in the mid-1990s, survival following HIV diagnosis has risen dramatically and HIV infection has evol

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… in HIV Epidemiology, Clinical Research 2007 Australian HIV Surveillance Report 23 1 Naylor K Li G Vallejo AN 2005 The influence of age on T cell generation and TCR diversity J Immunol 174 7446 52 15905594 10.4049/jimmunol.174.11.7446 Nelson M Fatkenheuer G Konourina I 2007 Efficacy and safety of maraviroc … adults: a review of strategies and interventions for improvement J Gerontol Nurs 30 33 43 15287325 10.3928/0098-9134-20040701-08 Schoenbaum EE Hartel D Lo Y 2005 HIV infection, drug use, and onset of natural menopause Clin Infect Dis 41 1517 24 16231267 10.1086/497270 Selzentry PI 2007 Selzentry™ (maraviroc …

Targeting cytokine and chemokine signaling pathways for cancer therapy.

Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles in both normal physiology and the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, and growth factors like TGF-β, VEGF, and EGF, can promote or inhibit tumor growth, influence the tumor microenvironment, and impact the efficacy of cancer treatments. Recent advances in targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate the immune system, inhibit tumor progression, and o

Molecular Approaches To Target GPCRs in Cancer Therapy

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… Maraviroc is a CCR5 antagonist recently approved by the FDA for this disease. Approval could open the way to trials testing Maraviroc as an anticancer agent. In a xenograft model of human breast cancer, the CXCR1 antagonist reparixin was able to specifically target the CSCs population. …

GvHD prophylaxis with tacrolimus, sirolimus, and mycophenolate mofetil after reduced intensity conditioning hematopoietic stem cell allogeneic transplantation.

We present the largest prospective real-world experience in 159 patients who received the triple combination of tacrolimus/sirolimus/mycophenolate mofetil after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC-alloHSCT) from matched-related (MRD), matched-unrelated (MUD) or mismatched-unrelated donors (MMURD). Despite the high-risk and elderly population, non-relapse mortality (NRM) at day +100 and 1 year was 5.1% and 8.6%. Grades 2-4 and 3-4 acute Graft-versus-host disease (GvHD) at day +180 was 30.3% and 13%, respectively. Chronic GvHD at 1 and 3 years w

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… Bolaños-Meade J Reshef R Fraser R Fei M Abhyankar S Al-Kadhimi Z Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host … Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity …

Janus kinase inhibition in the treatment and prevention of graft-versus-host disease.

Graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). For many years, corticosteroids have been the mainstay treatment for GVHD, but cases of steroid-refractory GVHD and the severe adverse effects of high-dose corticosteroids have increased the need for preventative and therapeutic strategies for GVHD. Due to the nature of alloreactive T cells, GVHD is inherently linked to the graft-versus-leukemia (GVL) effect, the therapeutic driving force behind stem cell transplantation. A considerable clinical ch

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… Maraviroc, an inhibitor of CCR5, a chemokine receptor involved in T cell trafficking, was also investigated but did not show superiority to standard of care with PTCy/Tacrolimus/MMF ( 57 , 58 ). Other approaches have included targeting cytokine signaling pathways, notably IL-6. … Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with. …

The progress and perspective of nanomedicine in modulating the tumor immune microenvironment.

The widespread application of nanomedicine in oncology is reshaping cancer treatment paradigms. Using the precise targeting mechanisms and the rapid advancements in nanoscale materials, nanomedicine is driving progress in cancer therapy, particularly within the complex landscape of the tumor immune microenvironment (TIM). This review provides a comprehensive overview of recent studies elucidating the critical role of nanomedicine in modulating the TIM, augmenting the efficacy of immunotherapies, and overcoming therapeutic resistance. Emphasis is placed on the significance of targeted drug deli

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… /gemcitabine/Paclitaxel and carboplatin/DOXIL®/Caelyx® doxorubicin HCL liposome injection) | Solid tumors | I | 2015 | NCT01204996 | 149 | PF-04136309 (CCR2 antagonist) | Combined chemotherapy (Oxaliplatin/Irinotecan/Leucovorin/Fluorouracil) | Pancreatic neoplasms | I | 2016 | NCT01413022 | 137 | Maraviroc … Maraviroc, as a CCR5 antagonist, was initiated in a clinical trial in 2022 in combination with Pembrolizumab for metastatic colorectal cancer 157 . Beyond inhibiting TAM recruitment, clinical trials are also exploring how to deplete and suppress TAMs. …

Potential Associations between Vascular Biology and Hodgkin's Lymphoma: An Overview.

Hodgkin's lymphoma (HL) is a lymphatic neoplasm typically found in the cervical lymph nodes. The disease is multifactorial, and in recent years, the relationships between various vascular molecules have been explored in the field of vascular biology. The connection between vascular biology and HL is intricate and the roles of several pathways remain unclear. This review summarizes the cellular and molecular relationships between vascular biology and HL. Proteins associated with various functions in vascular biology, including cytokines (TNF-α, IL-1, IL-13, and IL-21), chemokines (CXCL10, CXCL1

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… The study concluded that maraviroc, when used to block the CCL5-CCR5 pathway, effectively reduced tumor mass [ 118 ]. In a separate study involving male NSG mice, researchers sought to determine the efficacy of trabectedin on HL xenografts. … CCR5 Antagonism by Maraviroc Inhibits Hodgkin Lymphoma Microenvironment Interactions and Xenograft Growth. Haematologica. 2019;104:564–575. doi: 10.3324/haematol.2018.196725. 119. Casagrande N., Borghese C., Favero A., Vicenzetto C., Aldinucci D. …

Chemokines in COPD: From Implication to Therapeutic Use.

: Chronic Obstructive Pulmonary Disease (COPD) represents the 3rd leading cause of death in the world. The underlying pathophysiological mechanisms have been the focus of extensive research in the past. The lung has a complex architecture, where structural cells interact continuously with immune cells that infiltrate into the pulmonary tissue. Both types of cells express chemokines and chemokine receptors, making them sensitive to modifications of concentration gradients. Cigarette smoke exposure and recurrent exacerbations, directly and indirectly, impact the expression of chemokines and chem

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… Although very successful in some cases, attested by the example of plerixafor [ 143 ] and maraviroc [ 144 ], the respective antagonists of CXCR4 and CCR5, most of the pharmacological agents that target chemokine receptors inhibit both G protein signaling and β-arrestins-mediated endocytosis, promoting … Maraviroc for previously treated patients with R5 HIV-1 infection N. Engl. J. Med. 2008 359 1429 1441 10.1056/NEJMoa0803152 18832244 PMC3078519 145. Hitchinson B. Eby J.M. Gao X. Guite-Vinet F. Ziarek J.J. Abdelkarim H. Lee Y. Okamoto Y. Shikano S. Majetschak M. …

Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial.

Graft-versus-host disease (GVHD) is the most important complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). We performed a prospective randomized, multicenter, phase 3 trial to study whether posttransplant cyclophosphamide (PT-Cy) combined with a short course of cyclosporine A (CsA) would result in a reduction of severe GVHD and improvement of GVHD-free, relapse-free survival (GRFS) as compared with the combination of CsA and mycophenolic acid (MPA) after nonmyeloablative (NMA) matched related and unrelated peripheral blood alloHSCT. Between October 2013 and June 2018

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… Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity …

Immunotherapies for Aging and Age-Related Diseases: Advances, Pitfalls, and Prospects.

Aging is characterized by a gradual decline in the functionality of all the organs and tissues, leading to various diseases. As the global population ages, the urgency to develop effective anti-aging strategies becomes increasingly critical due to the growing severity of associated health problems. Immunotherapy offers novel and promising approaches to combat aging by utilizing approaches including vaccines, antibodies, and cytokines to target specific aging-related molecules and pathways. In this review, we summarize the recent advancements of immunotherapies to eliminate senescence cells and

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… Maraviroc | CCR5 | HIV, atherosclerosis | Small molecule | Maraviroc is an FDA-approved agent for HIV. In mouse model and preliminary data in humans, maraviroc showed anti-atherosclerotic effect. Further phase IV trial ( NCT03402815 ) is ongoing. …

Multicentre adaptive randomised trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin versus calcineurin inhibitor-based or sirolimus-based post-transplant cyclophosphamide (Methods of T cell Depletion, MoTD trial).

IntroductionGraft-versus-host disease (GvHD) remains a major complication of allogeneic stem cell transplantation (allo-SCT), affecting 30-70% of patients (representing 800 new patients per year in the UK). The risk is higher in patients undergoing unrelated allo-SCT. About 1 in 10 patients die as a result of GvHD or through complications of its treatment. In patients who survive GvHD and or the complications of treatment, about 1 in 3 patients develop chronic GvHD which has a negative impact on quality of life (QoL). Many transplant protocols use alemtuzumab or anti-thymocyte globulin (ATG) i

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… Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity …

Tacrolimus/methotrexate vs tacrolimus/reduced-dose methotrexate/mycophenolate for graft-versus-host disease prevention.

Tacrolimus (Tac)/methotrexate (MTX) is standard graft-versus-host disease (GVHD) prophylaxis; however, is associated with several toxicities. Tac, reduced-dose MTX (mini-MTX), and mycophenolate mofetil (MMF) have been used but never compared with standard MTX. We performed a randomized trial comparing Tac/MTX (full-MTX) with Tac/mini-MTX/MMF (mini-MTX/MMF) for GVHD prevention after allogeneic hematopoietic cell transplantation (HCT). Patients (pts) receiving first myeloablative HCT using an 8/8 HLA-matched donor were eligible. Primary end points were incidence of acute GVHD (aGVHD), mucositis,

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… Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity …

Identification of Novel Risk Variants of Inflammatory Factors Related to Myeloproliferative Neoplasm: A Bidirectional Mendelian Randomization Study.

Epidemiological and experimental evidence has linked chronic inflammation to the etiology of myeloproliferative neoplasm (MPN). However, it remains unclear whether genetic associations with specific inflammatory biomarkers are causal or due to bias. This study aimed to assess the effect of C-reactive protein (CRP) and systemic inflammatory regulators on MPN within a bidirectional Mendelian randomization design. Genetic associations with MPN were derived from a publicly available genome-wide association study (GWAS) comprising 1,086 cases and 407,155 controls of European ancestry. Additionally,

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… CCR5 antagonism by maraviroc inhibits Hodgkin lymphoma microenvironment interactions and xenograft growth. Haematologica. 2019;104(03):564–575. doi: 10.3324/haematol.2018.196725. 41. Popek-Marciniec S, Styk W, Wojcierowska-Litwin M et al. …

Impact of Early Intrapatient Variability of Tacrolimus Concentrations on the Risk of Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation Using High-Dose Post-Transplant Cyclophosphamide.

Tacrolimus (Tac) is a pivotal immunosuppressant agent used to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloHSCT). Tac is characterized by a narrow therapeutic window and a high inter-patient and intra-patient pharmacokinetic variability (IPV). Although high IPV of Tac concentrations has been associated with adverse post-transplant outcomes following solid organ transplantation, the effects of Tac IPV on alloHSCT recipients have not been determined. Tac IPV was therefore retrospectively evaluated in 128 alloHSCT recipients receiving high-dose post-tra

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… Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity …

Phase 2 study of natalizumab plus standard corticosteroid treatment for high-risk acute graft-versus-host disease.

Graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract is the main cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation. Ann Arbor (AA) scores derived from serum biomarkers at onset of GVHD quantify GI crypt damage; AA2/3 scores correlate with resistance to treatment and higher NRM. We conducted a multicenter, phase 2 study using natalizumab, a humanized monoclonal antibody that blocks T-cell trafficking to the GI tract through the α4 subunit of α4β7 integrin, combined with corticosteroids as primary treatment for patients with new onset AA2/3 GV

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… Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity …

EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients.

BackgroundThe coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that challenges public health-care systems worldwide. Endothelial cell dysfunction plays a key role in pathophysiology, and simple prognosticators may help to optimize allocation of limited resources. Endothelial activation and stress index (EASIX) is a validated predictor of endothelial complications and outcome after allogeneic stem cell transplantation. Aim of this study was to test if EASIX could predict life-threatening complications in pati

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… Patients were treated with standard supportive care including antibiotic and antifungal therapy, whereas additional immunomodulatory therapy was inconsistently applied (azithromycin, hydroxychloroquine, tocilicumab, anakinra, prednisolone, maraviroc, remdesivir, Cytosorb™, plasmapheresis). …

Plasmablastic Lymphoma. A State-of-the-Art Review: Part 2-Focus on Therapy.

The objective of this two-part review is to present a current and comprehensive understanding of the diagnosis and management of plasmablastic lymphoma. The first part, which was published previously, focused on the study of epidemiology, etiology, clinicopathological characteristics, differential diagnosis, prognostic variables, and the impact of plasmablastic lymphoma on specific populations. This second part addresses the difficult topic of the treatment of plasmablastic lymphoma, specifically examining both the conventional, consolidated approach and the novel therapeutic strategy.

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… The CCR5 antagonist maraviroc is a substrate for the CYP3A enzyme and the P glycoprotein. This means that strong CYP3A inducers or inhibitors may change the levels of maraviroc. …

Сопротивление лекарствам в Множественной миеломе: опухоль-интринтические механизмы и микроокружающая среда костного мозга.

Множественная миелома (ММ) — злокачественное расстройство плазменных клеток, и, несмотря на значительные улучшения в прогнозе, полученные благодаря химиотерапии, иммунной терапии и автологической трансплантации стволовых клеток, у большинства пациентов в конечном счете возникает рецидив или рефракторное заболевание. Сопротивление лекарствам (DR) все чаще признается как динамическо развивающаяся экосистема, формируемая из опухоли-интенсивной пластичности и непрерывной реконструкцией микроокружающей среды костного мозга (BMME), а не как одно молекулярное повреждение. В настоящем обзоре резюмирую

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… The CCR5 antagonist maraviroc suppresses M2 polarization and cooperates with BTZ to enhance cytotoxicity, supporting the CCL5/CCR5 axis as a complementary therapeutic target for further clinical translation [ 110 ] (Figure  5 ). …

A comparative analysis of transcriptomics of newly diagnosed multiple myeloma: exploring drug repurposing.

Multiple myeloma (MM) is an incurable malignant plasma cell disorder characterized by the infiltration of clonal plasma cells in the bone marrow compartment. Gene Expression Profiling (GEP) has emerged as a powerful investigation tool in modern myeloma research enabling the dissection of the molecular background of MM and allowing the identification of gene products that could potentially serve as targets for therapeutic intervention. In this study we investigated shared transcriptomic abnormalities across newly diagnosed multiple myeloma (NDMM) patient cohorts. In total, publicly available tr

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… DRUGBANK, IUPHAR/BPS RIMEGEPANT | CGRP Receptor Inhibitor | ADM | Migraine Treatment | DRUGBANK, ChEMBL, IUPHAR/BPS UBROGEPANT | CGRP Receptor Inhibitor | ADM | Migraine Treatment | DRUGBANK, ChEMBL, IUPHAR/BPS ERENUMAB | CGRP Receptor Inhibitor | ADM | Migraine Prophylaxis | DRUGBANK, ChEMBL, IUPHAR/BPS MARAVIROC …

Innovative therapeutic concepts of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral disease of the brain-caused by human polyomavirus 2. It affects patients whose immune system is compromised by a corresponding underlying disease or by drugs. Patients with an underlying lymphoproliferative disease have the worst prognosis with a mortality rate of up to 90%. Several therapeutic strategies have been proposed but failed to show any benefit so far. Therefore, the primary therapeutic strategy aims to reconstitute the impaired immune system to generate an effective endogenous antiviral response. Recently, an

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… Harel A Horng S Gustafson T Ramineni A Farber RS Fabian M Successful treatment of progressive multifocal leukoencephalopathy with recombinant interleukin-7 and maraviroc in a patient with idiopathic CD4 lymphocytopenia J Neurovirol 2018 24 652 655 29987583 10.1007/s13365-018-0657-x 43. …