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Systemic Sclerosis and Malignancy: A Review of Current Data.

Systemic sclerosis (SSc) is associated with increased risk of malignancy. The organ systems most commonly affected are the lungs, the breasts and the hematological system. Risk factors predisposing a SSc patient for development of malignancy are not well defined, and the pathogenic basis of the association is yet to be explained. The incidence of malignancies in SSc patients is variable from one report to another, but most importantly, questions regarding the role of immunosuppressive therapies and the effect of autoantibodies have weak or sometimes contradictory answers in most of the current

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… T-cell (sirolimus and alefacept) and B-cell (rituximab (RTX))-targeted therapies have provided encouraging results in some studies for the treatment of SSc as well. These immunosuppressive agents might play a role in development of malignancy in patients with SSc. …

:: 45th Ежегодное совещание Европейского общества по трансплантации крови и костного мозга: Врачи - сессия плаката.

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Каннабиноиды в условиях хронической боли: обзор истории, эффективности, применения и рисков.

Справочная информация/цели: Хроническая боль по-прежнему является широко распространенной и сложной проблемой в области здравоохранения, которая зачастую является устойчивой к обычным методам лечения, таким, как опиоиды, которые сопряжены со значительным риском зависимости и неблагоприятных последствий. Каннабиноиды, биоактивные соединения, полученные на заводе Cannabis Sativa, и их синтетические аналоги стали потенциальной альтернативой обезболиванию, используя их взаимодействие с эндоканнабиноидной системой для модуляции боли и воспаления. Методы: Были рассмотрены и обобщены нынешняя, развив

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… A second review of 603 cannabis users noted adverse reactions such as increased bleeding risk, altered mental status, difficulty inducing anesthesia, and gastrointestinal issues by combining cannabis with warfarin, valproate, tacrolimus, and sirolimus [ 112 ]. …

Burden of hospitalizations and outpatient visits associated with moderate and severe acute graft-versus-host disease in Finland and Sweden: a real-world data study.

PurposeThe aim of this study was to describe patient characteristics and quantify hospital stays and outpatient visits (H&OV) following diagnosis with moderate-to-severe acute graft-versus-host disease (aGVHD) in Finland and Sweden.MethodsA retrospective chart audit collected data from patient medical records of 3 specialized centers performing allogeneic hematopoietic stem cell transplantation (HSCT; Finland, n = 2; Sweden, n = 1). Eligible patients received allogeneic HSCT (January 1, 2016-June 30, 2017) from any donor source, were diagnosed with grade II-IV aGVHD (MAGIC or modified Glucksbe

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… Prophylactic regimen categories included ex vivo T-cell depletion, in vivo T-cell depletion (antithymocyte globulin [ATG], alemtuzumab, other), cyclosporine, steroid, tacrolimus, posttransplant cyclophosphamide, methotrexate, mycophenolate, sirolimus, and other. …

Clinical and healthcare burden of disease associated with cytomegalovirus in allogeneic hematopoietic stem cell transplantation - A retrospective single-center study.

BACKGROUND: CMV infection is a common complication in allogeneic hematopoietic stem cell transplantation (HSCT). We investigated the association of clinically significant CMV (CS-CMV) infection with clinical outcomes and healthcare resource utilization in allogeneic HSCT patients in Finland. METHODS: This retrospective study included adult patients who received their first allogeneic HSCT between January 1, 2013, and December 31, 2018, at the Turku University Hospital. Data were collected from the hospital data lake. Clinical and healthcare outcomes were investigated at one year and mortality

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… Sirolimus‐based graft‐versus‐host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis . …

Targeting PI3K/Akt/mTOR Signaling in Cancer.

The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways are two pathways crucial to many aspects of cell growth and survival, in physiological as well as in pathological conditions (e.g., cancer). Indeed, they are so interconnected that, in a certain sense, they could be regarded as a single, unique pathway. In this paper, after a general overview of the biological significance and the main components of these pathways, we address the present status of the development of specific PI3K, Akt, and mTOR inhibitors, from already registered medici

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… Development of mTOR Inhibitors as Anticancer Agents Rapamycin (sirolimus), an antifungal agent with immunosuppressive properties, was first isolated in 1975 from the soil of the island of Rapa Nui or Easter Island ( 20 ). …

Resveratrol: Molecular Mechanisms, Health Benefits, and Potential Adverse Effects.

Resveratrol (RES), a naturally occurring polyphenolic compound, has garnered significant attention due to its diverse biological activities, which include anti-inflammatory, antioxidant, and antiaging properties. This review synthesizes current evidence concerning the molecular mechanisms, therapeutic efficacy, and safety profile of RES across a variety of pathologies, with an emphasis on the latest research conducted in recent years. Mechanistically, RES is known to modulate critical signaling pathways such as the activation of sirtuin 1. These actions collectively contribute to the attenuati

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… . | Na Wang | 2023 | [ 141 ] RES, pharmacologic ascorbate and chloroquine | Pancreatic ductal adenocarcinoma | Synergistic cytotoxic effect | Kinga Makk‐Merczel | 2024 | [ 142 ] RES and sirolimus | Lymphangioleiomyomatosis | The addition of RES was safe and well tolerated in patients | Nishant Gupta …

The role of autophagy in cancer: from molecular mechanism to therapeutic window.

Autophagy is a cellular degradation process that plays a crucial role in maintaining metabolic homeostasis under conditions of stress or nutrient deprivation. This process involves sequestering, breaking down, and recycling intracellular components such as proteins, organelles, and cytoplasmic materials. Autophagy also serves as a mechanism for eliminating pathogens and engulfing apoptotic cells. In the absence of stress, baseline autophagy activity is essential for degrading damaged cellular components and recycling nutrients to maintain cellular vitality. The relationship between autophagy a

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… Cancer NCT04772846 | Phase I/II | CQ | Glioblastoma NCT02366884 | Phase II | CQ + Anti-Bacterial Agents/Anti-Fungal/Agent Anti-Protozoal Agents | Malignant disease NCT03400865 | Unknown | CQ | Prolactinoma NCT01023737 | Phase I | HCQ + Vorinostat | Malignant Solid Tumour NCT01266057 | Phase I | HCQ + Sirolimus … Vorinostat/Sirolimus | Advanced Cancers NCT03015324 | Phase I | HCQ | Solid Tumor NCT01273805 | Phase I | HCQ | Pancreatic Cancer NCT04145297 | Phase I | HCQ + Ulixertinib | Gastrointestinal Neoplasms NCT03377179 | Phase II | HCQ + ABC294640 | Cholangiocarcinoma NCT01006369 | Phase II | HCQ + Bevacizumab …

New landscapes and horizons in hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC), is the sixth most frequent form of cancer and leads to the fourth highest number of deaths each year. HCC results from a combination of environmental factors and aging as there are driver mutations at oncogenes which occur during aging. Most of HCCs are diagnosed at advanced stage preventing curative therapies. Treatment in advanced stage is a challenging and pressing problem, and novel and well-tolerated therapies are urgently needed. We will discuss further advances beyond sorafenib that target additional signaling pathways and immune checkpoint proteins. The

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… kinases | Sorafenib (Nexavar®, Bayer) + Trametinib | I | active, not recruiting | NCT02292173 PI3K Inhibitors PI3K, PD1 | SF1126 and Nivolumab | I | active, not recruiting | NCT03059147 PI3K-β and other kinases | GSK2636771 and other kinase inhibitors | I | recruiting | NCT02465060 mTORC1 mTORC1 | Sirolimus … The mTORC1 blocker rapamycin (a.k.a. sirolimus; Rapamune®, Wyeth Pharmaceuticals) has been examined in at least seven clinical trials with HCC patients. The combination of rapamycin and bevacizumab has been evaluated in at least one phase I clinical trial ( NCT00467194 ) with HCC patients. …

Treatment of Medication-Related Osteonecrosis of the Jaw Without and With the Use of Advanced Platelet-Rich Fibrin: A Retrospective Clinical Study.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is drug-induced bone destruction that is exposed for a minimum of 6 to 8 weeks in patients who have not received head and neck radiotherapy and who have not been diagnosed with facial bone metastases. MRONJ treatment outcomes are unpredictable. Therefore, alternative treatment methods are being explored, such as blood-derived platelet-rich preparations enriched with growth factors, including advanced platelet-rich fibrin (A-PRF). The presence of growth factors may enhance healing and reduce post-procedure complications. There are

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… bisphosphonates (BPs; alendronate, etidronate, ibandronate, clodronate, medronate, oxydronate, pamidronate, risedronate, tiludronate, and zoledronate), corticosteroids, denosumab (anti-RANKL), bevacizumab and aflibercept (anti-VEGFR), sunitinib, sorafenib, cabozatinib (tyrosine kinase inhibitors), sirolimus …

CAR T cell therapy for refractory pediatric systemic lupus erythematosus: a new era of hope?

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that can affect multiple organ systems and is heterogenous in its presentation and response to therapy. When diagnosed in childhood, SLE is associated with increased morbidity and mortality compared to adult SLE, often requiring substantial immunosuppression with the risk of significant side effects. There remains a significant unmet need for new therapies that can improve disease control and reduce glucocorticoid and other toxic medication exposure for patients with severe or refractory disease. The pathogenesis of SLE invol

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… 5 × 105/kg) | Still in moderate to severe disease activity despite ≥ 3 M of high dose glucocorticoids (prednisone ≥ 1 mg/kg/d or other equivalent amount of other steroids), hydroxychloroquine and at least 2 of the following treatments (CYC, MMF, azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus …

A phase 2 and pharmacological study of sapanisertib in patients with relapsed and/or refractory acute lymphoblastic leukemia.

BACKGROUND: Despite recent approval of several new agents, relapsed acute lymphoblastic leukemia (ALL) remains challenging to treat. Sapanisertib (MLN0128/TAK-228) is an oral TORC1/2 inhibitor that exhibited preclinical activity against ALL. METHODS: We conducted a single-arm multi-center Phase II study of sapanisertib monotherapy (3 mg orally daily of the milled formulation for 21 days every 28 days) in patients with ALL through the Experimental Therapeutics Clinical Trials Network (NCI-9775). RESULTS: Sixteen patients, 15 of whom were previously treated (median 3 prior lines of therapy), w

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… The natural product sirolimus (rapamycin) and its derivatives, which were the first identified mTOR inhibitors, not only modulate proliferation of normal T cells, 12 , 13 , 14 contributing to beneficial immunosuppressive effects, 15 , 16 but also impact survival of malignant lymphoid cells. 17 , 18 , …

How I treat microangiopathic hemolytic anemia in patients with cancer.

Microangiopathic hemolytic anemia (MAHA) with thrombocytopenia, suggests a thrombotic microangiopathy (TMA), linked with thrombus formation affecting small or larger vessels. In cancer patients, it may be directly related to the underlying malignancy (initial presentation or progressive disease), to its treatment, or a separate incidental diagnosis. It is vital to differentiate incidental thrombotic thrombocytopenia purpura or atypical hemolytic uremic syndrome in cancer patients presenting with a TMA, as they have different treatment strategies, and prompt initiation of treatment impacts outc

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… Pentostatin | Dose-dependent toxicity at high doses EGFR inhibitor cetuximab | Renal TMA with nephrotic syndrome Calcineurin inhibitors (eg, ciclosporin, tacrolimus) | TMA primarily affects glomerular arterioles; reducing dose or stopping drug can improve or reverse the TMA mTOR inhibitors (eg, sirolimus …

Association of stiff-person syndrome with autoimmune endocrine diseases.

BackgroundStiff-person syndrome (SPS) and its subtype, stiff limb syndrome (SLS), are rare neurological disorders characterized by progressive muscular rigidity and spasms. Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the production of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter of the central nervous system. SPS is an autoimmune disease triggered by anti-glutamic acid decarboxylase antibody (anti-GAD Ab). Clinically, anti-GAD Ab is associated with SPS, type 1 diabetes mellitus (T1DM), and other autoimmune diseases.AimTo investigate the link of autoimmune

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… Other immunomodulating agents such as mycophenolate mofetil, azathioprine, cyclophosphamide, cyclosporine, tacrolimus, and sirolimus may also give variable benefits[ 2 ]. Plasmapheresis can improve symptoms with severe SPS in previous studies[ 54 ]. …

Unraveling the Anti-Cancer Mechanisms of Antibiotics: Current Insights, Controversies, and Future Perspectives.

Cancer persists as a significant global health challenge, claiming millions of lives annually despite remarkable strides in therapeutic innovation. Challenges such as drug resistance, toxicity, and suboptimal efficacy underscore the need for novel treatment paradigms. In this context, the repurposing of antibiotics as anti-cancer agents has emerged as an attractive prospect for investigation. Diverse classes of antibiotics have exhibited promising anti-cancer properties in both in vitro and in vivo studies. These mechanisms include the induction of apoptosis and cell cycle arrest, generation o

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… Novel Macrolides Rapamycin, also known as sirolimus, is a macrolide antibiotic that is commonly administered for prophylaxis of renal graft rejection [ 65 ]. … Sirolimus: Its Discovery, Biological Properties, and Mechanism of Action. Transplant. Proc. 2003;35:7S–14S. doi: 10.1016/S0041-1345(03)00211-2. 66. Blagosklonny M.V. Cancer Prevention with Rapamycin. Oncotarget. 2023;14:342–350. doi: 10.18632/oncotarget.28410. 67. …

Repurposing anticancer drugs for the management of COVID-19.

Since its outbreak in the last December, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread worldwide at a pandemic proportion and thus is regarded as a global public health emergency. The existing therapeutic options for COVID-19 beyond the intensive supportive care are limited, with an undefined or modest efficacy reported so far. Drug repurposing represents an enthusiastic mechanism to use approved drugs outside the scope of their original indication and accelerate the discovery of new therapeutic options. With the emergence of COVID-19, drug repurposing has been la

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… Recently, a combination of dactinomycin and sirolimus showed a synergistic action against SARS-CoV-2-host proteins [ 225 ]. … Notably, the mTOR pathway is a target of sirolimus that has also shown a promising activity against MERS-CoV in addition to its known anticancer, immunosuppressive and antifungal properties [ 100 ]. …

Exploring the Influence of Oral and Gut Microbiota on Ulcerative Mucositis: A Pilot Cohort Study.

AIM: Comparing oral and gut microbiome profiles between patients with and without ulcerative mucositis during allogeneic stem cell transplantation (aSCT). MATERIALS AND METHODS: Specimens from oral mucosa, saliva, and stool were collected pre-(T0) and post- (T0 +28d ± 14d) aSCT (T1). Microbiome structure differences were analyzed by 16S-rRNA-gene sequencing, and associations to patients' clinical characteristics were investigated. RESULTS: Ten of 25 included patients developed ulcerations. The α-diversity decreased between T0 and T1, independent of ulcerations. PERMANOVA revealed differences

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… Other immunosuppressant drugs were CellCept, mycophenolate, Sirolimus, Tacrolimus, and different Glucocorticoids. All patients received Cotrim Forte as a broad‐spectrum antibiotic as part of their standard care. …

Nanomedicine for cancer patient-centered care.

Cancer is a leading cause of morbidity and mortality worldwide, and an increase in incidence is estimated in the next future, due to population aging, which requires the development of highly tolerable and low-toxicity cancer treatment strategies. The use of nanotechnology to tailor treatments according to the genetic and immunophenotypic characteristics of a patient's tumor, and to allow its targeted release, can meet this need, improving the efficacy of treatment and minimizing side effects. Nanomedicine-based approach for the diagnosis and treatment of cancer is a rapidly evolving field. Se

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… participants with diffuse large B‐cell lymphoma | Recruiting | Diffuse large B‐cell lymphoma, diffuse large B‐cell lymphoma germinal center B‐cell type, diffuse large B‐cell lymphoma, not otherwise specified, high grade B‐cell lymphoma | Ohio State University Comprehensive Cancer Center | NA NCT03660930 | Nab‐sirolimus … tumor | Dana‐Farber Cancer Institute | Phase 2 NCT05101616 | A pilot study of neoadjuvant chemotherapy with or without camrelizumab for locally advanced gastric cancer | Recruiting | Gastric cancer | Shanghai Minimally Invasive Surgery Center | Phase 1, Phase 2 NCT05103358 | Phase 2 basket trial of Nab‐sirolimus …

The Impact of Human Microbiotas in Hematopoietic Stem Cell and Organ Transplantation.

The human microbiota heavily influences most vital aspects of human physiology including organ transplantation outcomes and transplant rejection risk. A variety of organ transplantation scenarios such as lung and heart transplantation as well as hematopoietic stem cell transplantation is heavily influenced by the human microbiotas. The human microbiota refers to a rich, diverse, and complex ecosystem of bacteria, fungi, archaea, helminths, protozoans, parasites, and viruses. Research accumulating over the past decade has established the existence of complex cross-species, cross-kingdom interac

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… Current renal transplantation prophylaxis regimens involve an assortment of immunosuppressants such as mycophenolate mofetil, sirolimus, prednisone, and azathioprine, often with concomitant corticosteroid administration ( 132 , 170 , 171 ). … To complicate matters even further, some immunosuppressant drugs such as tacrolimus and sirolimus can function as a macrolide antibiotic ( 132 , 172 ). …

Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An

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… Active, not recruiting | ADT + abiraterone + prednisone Steroid | A Study of Nivolumab or Placebo in Combination with Docetaxel in Men with Advanced CRPC (CheckMate 7DX) | NCT04100018 | III | 1 February 2020 | 984 | Recruiting | Nivolumab + prednisone + docetaxel vs. placebo Immunosuppressive drug | Sirolimus …