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Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Governs GVHD and Immunosuppression Need, Reducing Late Toxicities in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

Combined direct antineoplastic activity and the long-lasting immunological effects of allogeneic hematopoietic cell transplant (HCT) can cure many hematological malignancies, but broad adoption requires non-relapse mortality (NRM) rates and graft-versus-host disease (GVHD) control. Recently, posttransplant cyclophosphamide (PTCy) given after a bone marrow transplant significantly reduced GVHD-incidence, while PTCy given with tacrolimus/mofetil mycophenolate (T/MMF) showed activity following allogeneic peripheral blood stem cell transplantation (alloPBSCT). Here, we report the experience of a l

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… These strategies include: PTCy after BMT-HCT (39–60% aGVHD and 6–21% cGVHD), ATG-based regimens (23–56% aGVHD, and 16–31% cGVHD), and T/MMF/Sirolimus regimens (26% aGVHD and 49% cGVHD) [ 13 , 14 , 15 , 16 , 18 , 19 , 20 , 33 , 44 , 45 ]. … Addition of sirolimus to standard cyclosporine plus mycophenolate mofetil-based graft-versus-host disease prophylaxis for patients after unrelated non-myeloablative haemopoietic stem cell transplantation: A multicentre, randomised, phase 3 trial. …

What the Intensivist Needs to Know About Hematopoietic Stem Cell Transplantation?

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… Patients typically receive additional immunosuppressive therapy with calcineurin inhibitors (i.e., tacrolimus, sirolimus), mycophenolate mofetil (CellCept®), and/or other drugs (methotrexate, anti-thymocyte globulin) to both prevent rejection of the graft and protect normal recipient/host cells from … This can be accomplished through manipulation of the graft to deplete the T-cell population or with pharmacologic agents (e.g., methotrexate, cyclosporine, and the calcineurin inhibitors tacrolimus or sirolimus). …

Acute interstitial nephritis - a reappraisal and update.

Acute interstitial nephritis (AIN) is an under recognized and under diagnosed cause of acute kidney injury (AKI). It is estimated to account for 15 - 20% of cases of AKI; it is the reported diagnosis in 2.8% of all kidney biopsies, and 13.5% of biopsies done specifically for acute renal failure. Considerable evidence implicates antigen initiated cell-mediated injury in the pathogenesis of AIN. Drugs account for 70% of all cases, with over 150 different agents incriminated. The remaining cases are due to infections, autoimmune diseases, and rarely idiopathic. The central component of renal inju

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… hydroxyethyl starch, interleukin, isotretinoin, immunoglobulin, griseofulvin, kudzu root juice, levetiracetam, liraglutide, methyldopa, paraphenylene diamine, phenazopyridine, phendimetrazine, phenobarbitol, phenteramine, phenytoin, piperazine, propylthiouracil, quinine, rosiglitazone, rosuvastatin, sirolimus … hydroxyethyl starch, interleukin, isotretinoin, immunoglobulin, griseofulvin, kudzu root juice, levetiracetam, liraglutide, methyldopa, paraphenylene diamine, phenazopyridine, phendimetrazine, phenobarbitol, phenteramine, phenytoin, piperazine, propylthiouracil, quinine, rosiglitazone, rosuvastatin, sirolimus …

Early termination of cardiovascular trials as a consequence of poor accrual: analysis of ClinicalTrials.gov 2006-2015.

ObjectivesTo present a snapshot of experimental cardiovascular research with a focus on geographical and temporal patterns of early termination due to poor accrual.SettingThe Aggregate Analysis of ClinicalTrials.gov (AACT) database, reflecting ClinicalTrials.gov as of 27 March 2016.DesignThe AACT database was searched for all cardiovascular clinical trials that started from January 2006 up to December 2015.ResultsThirteen thousand and seven hundred twenty-nine cardiovascular trials were identified. Of these, 8900 (65%) were classified as closed studies. Globally, 11% of closed trials were term

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… A randomized, prospective, intercontinental evaluation of a bioresorbable polymer sirolimus-eluting coronary stent system: the CENTURY II (Clinical evaluation of New Terumo Drug-Eluting Coronary Stent System in the treatment of patients with coronary artery disease) trial. …

Keyword Index for Volume 111

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… 2091, 2254 scFv antibody 551 screening 577, 965, 1421, 1440, 1542, 2076, 2152, 2235 seasonality 1810 self-sampling 1095, 2187 sensitivity 1734 sensor 790 sequencing 17, 1047 serpinA1 1993 Serpine 2114 serum 2163 SFPQ 736 SHIVA 17 SHP-2 1327 signal transduction 2103 SINE 281 siRNA 1180 sirolimus …

Potential Molecular Targeted Therapy for Unresectable Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers, representing a serious worldwide health concern. The recurrence incidence of hepatocellular carcinoma (HCC) following surgery or ablation is as high as 70%. Thus, the clinical applicability of standard surgery and other locoregional therapy to improve the outcomes of advanced HCC is restricted and far from ideal. The registered trials did not identify a treatment that prolonged recurrence-free survival, the primary outcome of the majority of research. Several investigator-initiated trials have demonstrated that var

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… NCT00321594 | I/II | DLT/MTD | | Completed Bevacizumab + Erlotinib | NCT00365391 | II | ORR | TTP/PFS/OS | Completed Bevacizumab + Temsirolimus | NCT01010126 | II | CR + PR/T | - | Completed Sorafenibtosylate | NCT01502410 | II | CR + PR | T/PK | Completed Biological: -205/NY-ESO-1 Fusion Protein CDX-1401 ± Sirolimus … The three inhibitors that are most frequently used in clinical settings are sirolimus, everolimus, and temsirolimus. …

Using Prognosis-Related Gene Expression Signature and Connectivity Map for Personalized Drug Repositioning in Multiple Myeloma.

BACKGROUND Multiple myeloma (MM) is the second most common hematologic cancer with poor prognosis. Novel therapeutic strategies are needed to decrease the high mortality rate. The aim of this study was to identify prospective agents for MM. MATERIAL AND METHODS A microarray dataset was mined, which contains the transcriptome profiles of 588 MM patients. Univariate Cox analysis was performed to analyze the relationships between genes and clinical outcome. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were determined. Protective and risky genes were uploaded to Connec

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… The top 10 most significant potential molecules were vorinostat, trifluoperazine, thioridazine, prochlorperazine, trichostatin A, LY-294002, sirolimus, resveratrol, sulconazole, and norcyclobenzaprine ( Figure 5 ). The chemical structures of these molecules were also downloaded ( Figure 6 ). …

Outcomes of hematopoietic SCT recipients with rhinovirus infection: a matched, case-control study.

The impact of rhinovirus in hematopoietic SCT (HSCT) recipients is not well defined. A retrospective, matched, case-control study of HSCT recipients with rhinovirus was conducted between 2009 and 2011. Controls were matched for timing relative to transplant, malignancy, and stem cell source. There were 47 cases and 94 controls. The cases and controls did not differ with respect to age, gender, ethnicity, donor source, malignancy, conditioning regimen, immunosuppression, antimicrobial prophylaxis or significant comorbidities. There were no differences in need for intensive care unit care, 100 d

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… 17.0% (8) | 10.6% (10) | 0.28 Conditioning regimen Ablative | 54.4% (25) | 51.6% (48) | 0.76 Non-myeloablative | 45.6% (21) | 48.4% (45) | Immunosuppresive therapy Tacrolimus | 27.7% (13) | 28.7% (27) | 0.90 Corticosteroids | 25.5% (12) | 16% (15) | 0.17 Mycophenolate | 12.8% (6) | 4.3% (4) | 0.06 Sirolimus …

Transcription and Translation Inhibitors in Cancer Treatment.

Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the "undruggable" transcription factors and RNA molecules can also be targ

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… Rapamycin Rapamycin (sirolimus, Figure 7 ) is an antifungal molecule produced by Streptomyces hygroscopicus and it was first discovered from a soil sample from the Easter Island (Rapa Nui) (Vézina et al., 1975 ). …

Reciprocal regulation by TLR4 and TGF-β in tumor-initiating stem-like cells.

Tumor-initiating stem-like cells (TICs) are resistant to chemotherapy and associated with hepatocellular carcinoma (HCC) caused by HCV and/or alcohol-related chronic liver injury. Using HCV Tg mouse models and patients with HCC, we isolated CD133(+) TICs and identified the pluripotency marker NANOG as a direct target of TLR4, which drives the tumor-initiating activity of TICs. These TLR4/NANOG-dependent TICs were defective in the TGF-β tumor suppressor pathway. Functional oncogene screening of a TIC cDNA library identified Yap1 and Igf2bp3 as NANOG-dependent genes that inactivate TGF-β signali

The double-edged sword of tumor-targeted treatment: the influence of targeted therapy on the heart.

As an important means of modern cancer treatment, targeted therapy has significant efficacy, but cardiac toxicity cannot be ignored. From subclinical myocardial injury to severe heart failure (HF), it poses significant challenges to the long-term survival and quality of life of patients. This article summarizes the impact of targeted therapy drugs on cardiac function and their mechanisms, including cardiomyocyte damage, myocardial hypertrophy, and HF, and conducts in-depth research into potential molecular mechanisms. These include direct cardiomyocyte damage through targeted pathway inhibitio

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… Preclinical data indicate that sirolimus can inhibit myocardial hypertrophy and fibrosis. … Mechanistically, sirolimus reduces the proliferation of cardiac fibroblasts and collagen production, as well as the expression of pro-fibrotic genes (such as BNIP3 ) and extracellular matrix-related genes ( 48 ). …

2020 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference.

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… The patient was then started on sirolimus for an “APDS-like syndrome” despite the lack of genetic confirmation. Six months after introduction of mTOR inhibitor, his abdominal pain had completely disappeared. …

Biologics in Kidney Transplantation: Why and How Should We Personalize Their Dosage?

The therapeutic arsenal of immunosuppressive drugs in kidney transplantation has recently expanded with the introduction of biologics, approved or used off-label, that specifically target the immune system. Although therapeutic drug monitoring is well established for calcineurin inhibitors, its utility for biological immunosuppressants remains unclear. The objective of this narrative review was to evaluate whether biologics used to prevent or treat renal allograft rejection could be suitable candidates for therapeutic drug monitoring. This review provides (1) a comprehensive and up-to-date syn

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… Small-molecule drugs, including calcineurin inhibitors (tacrolimus and cyclosporine), mechanistic target of rapamycin inhibitors (everolimus, sirolimus), corticosteroids, and mycophenolate mofetil have long been the cornerstone of immunosuppressive regimens. … Therapeutic drug monitoring of sirolimus: correlations with efficacy and toxicity. Clin Transplant. 2000;14(2):97–109. 10.1034/j.1399-0012.2000.140201.x. 10770413 10.1034/j.1399-0012.2000.140201.x 4. …

Pathological Fractures in Rare Bone Diseases: Clinical Cases.

Rare bone diseases, though uncommon, present significant diagnostic and therapeutic challenges due to their clinical variability and overlapping symptoms with more prevalent conditions. This article describes a clinical case series of three patients with bone fragility fractures caused by rare bone diseases - primary hyperparathyroidism with brown tumor, Gorham-Stout disease, and alkaptonuria - treated at the Department of Orthopedic and Traumatology of Pisa University Hospital between 2018 and 2023. Each case highlights the diagnostic complexities, including inconclusive biopsies, nonspecific

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… Gorham-Stout disease successfully treated with sirolimus (rapamycin): a case report and review of the literature. BMC Musculoskelet Disord . 2020;21(1):577. doi: 10.1186/s12891-020-03540-7. 20. Schneider KN, Masthoff M, Gosheger G, et al. …

После-пересадки двойное злодейство: Множественная миелома и папиллярная рентгеновская ячейка Карцинома-А.

Фон и клиническая значимость: получатели почечных трансплантаций имеют 2-4-fold более высокий риск раковых заболеваний по сравнению с населением в целом. Целостное появление карциномы миеломы (ММ) и почечной клетки коренных почек (КЦК) является редким явлением и создает конкурирующие приоритеты между эффективностью борьбы с миломой и сохранением сплава. Представление дела: A 54-year-old с женщиной 2020 Пересадка живой донорской почки 2024 с болью в костях и опухолью плеча. КТ всего тела с низкой дозой выявила множественные остеолитические повреждения. Проверка показала, что М-протеин ИгГ. 38.5

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… Sirolimus and mTOR Inhibitors: A Review of Side Effects and Specific Management in Solid Organ Transplantation Drug Saf. 2019 42 813 825 10.1007/s40264-019-00810-9 30868436 42. Vural A.T. Togral A.K. Gulec A.T. Haberal M. …

Autoimmune Cytopenias Post Hematopoietic Stem Cell Transplantation in Pediatric Patients With Osteopetrosis and Other Nonmalignant Diseases.

Autoimmune cytopenia (AIC) is a rare complication post hematopoietic stem cell transplantation (HSCT), with a higher incidence in nonmalignant diseases. The etiology of post-HSCT AIC is poorly understood, and in many cases, the cytopenia is prolonged and refractory to treatment. Diagnosis of post-HSCT AIC may be challenging, and there is no consensus for a standard of care. In this retrospective study, we summarize our experience over the past five years with post-HSCT AIC in pediatric patients with osteopetrosis and other nonmalignant diseases. All pediatric patients who underwent HSCT for no

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… Sirolimus is Effective in Relapsed/Refractory Autoimmune Cytopenias: Results of a Prospective Multi-Institutional Trial. Blood (2016) 127:17–28. doi: 10.1182/blood-2015-07-657981 20. Hess J, Su L, Nizzi F, Beebe K, Magee K, Salzberg D, et al. …

A Future for Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes.

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… The adverse events of, for instance, DMARD, TNF blockers, sirolimus, cyclosporine, azathioprine, prednisone, thymoglobulin, alemtuzumab, or imatinib, all considered in the context of T1D, are certainly not negligible. …

Long term renal survival in patients undergoing T-Cell depleted versus conventional hematopoietic stem cell transplants.

Calcineurin inhibitor (CNI)-sparing T-cell depleted (TCD) hematopoietic stem cell transplants (HSCTs) are presumed to be less nephrotoxic than conventional HSCTs. We evaluated incidence and risk factors for kidney failure and chronic kidney disease (CKD) in 231 TCD and 212 conventional HSCT recipients. Kidney failure required a median glomerular filtration rate (GFR) 2 for ⩾100 days anytime after 180-days post-HSCT. Two-year cumulative incidence (CI) of kidney failure was 42% in the conventional versus 31% in the TCD group (P=0.005). TCD, age, acute kidney injury and number of toxic CNI levels

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… Those transplanted with conventional volunteer donor grafts received prophylaxis with tacrolimus plus methotrexate or tacrolimus plus sirolimus +/− methotrexate. Cyclosporine and mycophenolate were used with DUCB grafts. …

Transplantation Tolerance through Hematopoietic Chimerism: Progress and Challenges for Clinical Translation.

The perception that transplantation of hematopoietic stem cells can confer tolerance to any tissue or organ from the same donor is widely accepted but it has not yet become a treatment option in clinical routine. The reasons for this are multifaceted but can generally be classified into safety and efficacy concerns that also became evident from the results of the first clinical pilot trials. In comparison to standard immunosuppressive therapies, the infection risk associated with the cytotoxic pre-conditioning necessary to allow allogeneic bone marrow engraftment and the risk of developing gra

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… After 3 months, Tacrolimus was replaced by Sirolimus (Rapamycin) and mycophenolate mofetil was discontinued between 12 and 18 months and Sirolimus after 24 months. …

Повышение степени вероятности инфекционных осложнений, связанных с оральным мукоситом, после трансплантации ячеек гематопоэтического ствола: систематический обзор и метаанализ результатов и факторов риска.

Мукосит с желудочно-кишечным, вагинальным и носовым слизью one - первичные дозы, ограничивающие токсичность трансплантации стволовых клеток (ХХСТ) и режима кондиционирования. Повсеместно затрагивается орофаринговая слизь, которая может нанести ущерб здоровью и качеству жизни пациентов. Несмотря на его значительное распространение и пагубные последствия, мы недостаточно понимаем факторы риска и результаты, связанные с пероральным слизистым мукоситом (ОМ). Мы провели поиск литературы через PubMed и EBCO (прием 31 Март 2024) в соответствии с предпочтительными руководящими принципами, касающимися

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… MAC (BUCY or CYTBI) | RIC (FLUBU, FLUCY, FLUTBI, FLUCYTBI, or CY) | Karolinska University Hospital, Huddinge, Sweden | Patients scheduled for HSCT (n = 77) | WHO OM grading | OM (grades 1–2 and 3–4) and serum and gingival crevicular fluid cytokine levels Legert et al., 2021 [ 46 ] | RCT | Tacrolimus/Sirolimus … Oral mucositis after tacrolimus/sirolimus or cyclosporine/methotrexate as graft-versus-host disease prophylaxis. Oral Dis. 2021;27:1217–1225. doi: 10.1111/odi.13663. 47. Nath C.E., Trotman J., Tiley C., Presgrave P., Joshua D., Kerridge I., Kwan Y.L., Gurney H., McLachlan A.J., Earl J.W., et al. …