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Gene and Cell Therapy for Sarcomas: A Review.

Background: The heterogeneity of sarcomas and resulting distinct sub-type specific characteristics, their high recurrence rates, and tendency for distant metastasis, continue to present significant challenges to providing optimal treatments. Objective: To provide a comprehensive review of current literature and clinical trials in gene and cell therapies for sarcomas. Methods: A comprehensive literature search was conducted utilizing the following databases: PubMed, Medline, Google Scholar and clinicaltrials.gov. Search terms included "gene therapy", "cell therapy", "NK cell therapy, "CAR-T the

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… For sarcomas with specific mutations such as NTRK gene rearrangements, entrectenib and larotrectenib are very effective and are commonly used for sarcomas harboring these mutations and nab-sirolimus is approved for a rare sarcoma known as Perivascular epithelioid cell tumor (PEComa). …

Multidisciplinary Management of Morbidities Associated with Chronic Graft-Versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) represents a common long-term complication after allogeneic hematopoietic stem cell transplantation (HSCT). It imposes a significant morbidity burden and is the leading cause of non-relapse mortality among long-term HSCT survivors. cGVHD can manifest in nearly any organ, severely affecting the quality of life of a transplant survivor. While the mainstay of treatment has remained systemic immunosuppression with glucocorticoids, progress has been made within the last few years with approvals of three oral agents to treat steroid-refractory cGVHD: ibrutin

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… ruxolitinib, ibrutinib, and belomosudil for SR cGVHD may be constrained in many countries. 29,30 More accessible immunosuppressive drugs that are commonly used second-line after steroids include calcineurin inhibitors (tacrolimus and cyclosporine), methotrexate, mycophenolate mofetil, mTOR inhibitors (sirolimus …

Low-dose anti-thymocyte globulin plus low-dose post-transplant cyclophosphamide-based regimen for prevention of graft-versus-host disease after haploidentical peripheral blood stem cell transplants: a large sample, long-term follow-up retrospective study.

INTRODUCTION: The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined. METHODS: We performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis. RESULTS: The study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid

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… Sirolimus-based graft-versus-host disease prophylaxis promotes the in vivo expansion of regulatory T cells and permits peripheral blood stem cell transplantation from haploidentical donors. Leukemia (2015) 29(2):396–405. doi: 10.1038/leu.2014.180 45. …

Recent Advances of Acute Kidney Injury in Hematopoietic Cell Transplantation.

Acute kidney injury (AKI) is a common complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is associated with non-relapse mortality (NRM) and quality of life (QOL). Multiple factors may contribute to AKI during allo-HCT and are often present at the same time making it difficult to determine the cause of AKI in each patient. Nephrotoxic drugs, infections, thrombotic microangiopathy (TMA), and sinusoidal obstruction syndrome (SOS) are well described causes of AKI during allo-HCT. Acute graft-versus-host disease (aGVHD) is a major complication of allo-HCT that mainly targe

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… A Time-to-Event Model for Acute Kidney Injury After Reduced-Intensity Conditioning Stem Cell Transplantation Using a Tacrolimus- and Sirolimus-Based Graft-Versus-Host Disease Prophylaxis . …

Liver Disease Associated with Non-Hepatitis Viruses

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… Development of Kaposi's sarcoma under sirolimus-based immunosuppression and successful treatment with imiquimod Transplant Infectious Disease 10 2008 59 62 17428275 10.1111/j.1399-3062.2007.00239.x Barnett E.D. …

Recent advances in anti-angiogenic therapy of cancer.

Since angiogenesis is critical for tumor growth and metastasis, anti-angiogenic treatment is a highly promising therapeutic approach. Thus, for over last couple of decades, there has been a robust activity aimed towards the discovery of angiogenesis inhibitors. More than forty anti-angiogenic drugs are being tested in clinical trials all over the world. This review discusses agents that have approved by the FDA and are currently in use for treating patients either as single-agents or in combination with other chemotherapeutic agents.

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… These include: deforolimus, everolimus, rapamycin (sirolimus), and temsirolimus [ 104 , 105 ]. Temsirolimus (Toricel™) is a small molecule inhibitor of mTOR, approved for treating advanced renal cell carcinoma [ 106 ]. …

Cellular senescence-from solid organs to vascularized composite allotransplants.

Vascularized composite allotransplantation (VCA) has emerged as a novel therapy approach to restore form and function in patients with severe tissue defects of the face, hand, and abdominal wall, among other anatomical regions. The composite allografts comprise different tissues such as skin, muscle, or bone. Clinical data demonstrate promising mid- and long-term outcomes following VCA surgery, but our understanding of the cellular interactions and molecular pathways in VCA surgery is oftentimes deduced from solid organ transplantation (SOT). In SOT, the concept of cellular senescence has grow

Указываемые данные об автономной и аллогенетической трансплантации гематопоэтики стем-целлов у взрослых: состояние искусства.

Пересадка стволовых клеток (ХХСТ) гематополиетическая трансплантация превратилась из процедуры спасания лейкемии в лечебную форму, охватывающую почти все виды гематологической злокачественности и несколько ненасыщенных расстройств. Современный ландшафт был видоизменен тремя совпадающими силами: усовершенствованием стратификации с учетом конкретных рисков заболеваний (European LeukemiaNet [ELN] 2022 для острой миелоидной лейкемии, Молекулярной международной системы прогнозирования (IPSS-M) для миэлодипластических синдромов, Международной системы мутационного скручивания [MIPSS70+ v.2.0] и Myelo

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… Acquired pure red cell aplasia is managed medically (ciclosporin, rituximab, sirolimus), with transplantation as an exception [ 233 ]. … Ongoing trials are testing whether the calcineurin inhibitor can be replaced by sirolimus, or whether the intensity of the PTCy/calcineurin/mycophenolate backbone can be de-escalated in lower-risk transplants, but none of these variants has yet supplanted the standard triple combination. …

CAR-T Cell Therapy in Hematological Malignancies: Current Opportunities and Challenges.

Chimeric antigen receptor T (CAR-T) cell therapy represents a major breakthrough in cancer treatment, and it has achieved unprecedented success in hematological malignancies, especially in relapsed/refractory (R/R) B cell malignancies. At present, CD19 and BCMA are the most common targets in CAR-T cell therapy, and numerous novel therapeutic targets are being explored. However, the adverse events related to CAR-T cell therapy might be serious or even life-threatening, such as cytokine release syndrome (CRS), CAR-T-cell-related encephalopathy syndrome (CRES), infections, cytopenia, and CRS-rela

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… Clinically, red blood cell and platelet transfusions and hematopoietic growth factors, such as granulocyte colony-stimulating factor (G-CSF) and thrombopoietin (TPO), as well as TPO receptor agonists and sirolimus, are able to ameliorate cytopenia ( 154 , 155 ). … Case Report: Sirolimus Alleviates Persistent Cytopenia After CD19 CAR-T-Cell Therapy . Front Oncol ( 2021 ) 11 : 798352 . doi: 10.3389/fonc.2021.798352 35004324 PMC8733571 156 Wang Y Qi K Cheng H Cao J Shi M Qiao J . …

The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians Poster Session (P001-P706).

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Dental implants in immunocompromised patients: a systematic review and meta-analysis.

ObjectiveImpaired health conditions and related lack of adequate host healing are among the most important conditions that account for dental implant failure. Today clinicians face an increasing number of immunocompromised patients requesting implant-based rehabilitation. To provide clinical evidence for prospective decision-making, the aim of this systematic review and meta-analysis was to analyse the influence of immunodeficiency on dental implant survival.MethodsThe study was conducted according to the PRISMA Statement and the principles of the Cochrane Collaboration. MEDLINE and Web of Sci

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… As immunosuppressive drugs tacrolimus, sirolimus, cyclosporine, and mycophenolate were used, steroid prednisolone was applied. The indication for immunosuppression was a liver transplantation in 26 patients and a heart transplantation in 13 patients. …

Liposomal Drug Delivery Systems and Anticancer Drugs.

Cancer is a life-threatening disease contributing to ~3.4 million deaths worldwide. There are various causes of cancer, such as smoking, being overweight or obese, intake of processed meat, radiation, family history, stress, environmental factors, and chance. The first-line treatment of cancer is the surgical removal of solid tumours, radiation therapy, and chemotherapy. The systemic administration of the free drug is considered to be the main clinical failure of chemotherapy in cancer treatment, as limited drug concentration reaches the tumour site. Most of the active pharmaceutical ingredien

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… The Effects of Lyophilization on the Physico-Chemical Stability of Sirolimus Liposomes Adv. Pharm. Bull. 2013 3 25 29 24312808 10.5681/apb.2013.005 PMC3846045 42. Ball R.L. Bajaj P. Whitehead K.A. …

Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials.

BackgroundElucidation of mechanisms regulating bone metastasis has progressed significantly in recent years and this has translated to many new therapeutic options for patients with bone metastatic cancers. However, the rapid rate of progress in both the basic science literature and therapies undergoing clinical trials makes staying abreast with current developments challenging. This review seeks to provide an update on the current state of the science in bone metastasis research and give a snap shot of therapies in clinical trials for bone metastatic cancer.Main bodyBone metastasis represents

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… radiotherapy vs SBRT | NCT02512965 | | | | | | Observation vs SBRT vs SBRT +18F–DCFPyL | | NCT02680587 | | | | | Small Molecule | Zoledronic acid (prevention) | | | | | | NCT02622607 | NCT02286830 Docetaxel + zoledronic acid +/− apatinib | | | | | | NCT03127319 | Dose escalation of sirolimus …

Nephrotoxicity of recent anti-cancer agents.

Cancer patients may develop a variety of kidney lesions that impair not only their immediate survival but also limit the adequate treatment of the underlying malignant process. This review summarizes the nephrotoxic potential of some of the most recently developed anti-cancer drugs, focusing on those interfering with the vascular endothelial growth factor and epidermal growth factor receptor pathways and mammalian target of rapamycin inhibitors. Thrombotic microangiopathy (haemolytic-uraemic syndrome), proteinuria, hypertension and magnesium depletion are the most common side effects. Also the

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… The importance of mTOR in health and diseases has promoted the development of molecules that inhibit mTOR signalling, including rapalogs (sirolimus, temsirolimus, everolimus and deforolimus), which complex with FK506-binding protein 12 to inhibit mTOR complex 1 activity, or the more recent ATP competitive …

Dynamic Evolution of the Tumor Immune Microenvironment in Malignant Tumors and Emerging Therapeutic Paradigms.

Cancer is more than just a collection of tumor cells. The complex tumor system, including the tumor immune microenvironment (TIME), is continually changing. Tumor cells are in constant communication with all stromal elements (e.g., fibroblasts, endothelial cells, and extracellular matrix) and immune effector cells (e.g., T cells, B cells, natural killer cells, dendritic cells, macrophages, and myeloid-derived suppressor cells). Together, these intricate interactions among cell and molecular signaling pathways collectively drive tumor growth, tumor invasion, and metastasis and significantly aff

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… Targeting the lactate metabolism pathway Targeted molecules | Drug use | Tumor type | Clinical phase | Clinical serial number MCT1 | AZD3965 | Advanced tumor | Phase I | NCT01791595 mTOR | SAR245409 | Solid tumors | Phase Ib | NCT01390818 | TAK‐228 | Soft tissue sarcomas | Phase II | NCT02987959 | Sirolimus … | Advanced solid tumors/NSCLC | Phase I | NCT05840510 | Sirolimus | Malignant peripheral nerve sheath tumors | Phase II | NCT03433183 | BEZ235 | Advanced solid tumors | Phase I | NCT01343498 | Everolimus | Diffuse large B‐cell lymphoma | Phase Ib/II | NCT01854606 | AZD2014 | Solid cancer | Phase …

Infections in Recipients of Hematopoietic Stem Cell Transplants

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… Cyclosporine, tacrolimus, mycophenolate mofetil, methotrexate, or sirolimus (and other agents) are often used for weeks to months after allografting to lessen the risks and severity of GVHD. … Effective immunosuppressive agents for the prevention of GVHD include calcineurin inhibitors (cyclosporine or tacrolimus) with or without methotrexate, myco­phenolate mofetil, and sirolimus; they are usually started before transplantation. …

The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians Oral Session (O010-O173).

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Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management.

Drug-induced thrombotic microangiopathy (DITMA) represents 10%-13% of all thrombotic microangiopathy (TMA) cases and about 20%-30% of secondary TMAs, just behind pregnancy-related and infection-related forms. Although the list of drugs potentially involved as causative for TMA are rapidly increasing, the scientific literature on DITMA is quite scarce (mostly as individual case reports or little case series), leading to poor knowledge of pathophysiological mechanisms and clinical management. In this review, we focused on these critical aspects regarding DITMA. We provided an updated list of TMA

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… (alpha, beta,polycarboxylate) | Rifampicin | Estrogen/Progesterone Oxaliplatin | Palbociclib | Leflunomide | Sulfisoxazole | Hydroxychloroquine Pegylated liposomaldoxorubicin | Pazopanib | Muromonab-CD3 (OKT3) | Trimethoprim-sulfamethoxazole | Oxycodone hydrochloride ER Pentostatin | Regorafenib | Sirolimus …

Spectrum of histiocytic neoplasms associated with diverse haematological malignancies bearing the same oncogenic mutation.

Histiocytic disorders are a spectrum of rare diseases characterised by the accumulation of macrophage-, dendritic cell-, or monocyte-differentiated cells in various tissues and organs. The discovery of recurrent genetic alterations in many of these histiocytoses has led to their recognition as clonal neoplastic diseases. Moreover, the identification of the same somatic mutation in histiocytic lesions and peripheral blood and/or bone marrow cells from histiocytosis patients has provided evidence for systemic histiocytic neoplasms to originate from haematopoietic stem/progenitor cells (HSPCs). H

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… dramatic responses to selective inhibition of RET (Selpercatinib) or ALK (Crizotinib) have been observed in two patients with histiocytic neoplasms driven by rare rearrangements involving one of these genes [ 10 ], and high response rates have been described in ECD patients treated with the mTOR inhibitor Sirolimus …

The Contribution of Spanish Science to Patents: Medicine as Case of Study.

Investments in research and development (R&D) and innovation are expensive, and one wishes to be assured that there is positive feedback and to receive guidance on how to direct investments in the future. The social or economic benefits of investments in R&D are of particular interest to policymakers. In this regard, public expense in research, especially through universities, is sometimes being questioned. This paper establishes a measure of how research in Spain, and specifically in its universities, is involved. In this study, we have analyzed all the literature cited in the period 1998-201

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… multiple | 13 Activated-Leukocyte Cell Adhesion Molecule, T-Lymphocytes, Activated leukocyte | 12 Colorectal Neoplasms, Drug Therapy, Colorectal cancer | 11 Colorectal Neoplasms, Mutation, Anti-epidermal growth | 10 Breast Neoplasms, Receptor, Epidermal Growth Factor, Immunohistochemistry (IHC) | 9 Sirolimus …