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The Three Musketeers in Cancer Therapy: Pharmacokinetics, Pharmacodynamics and Personalised Approach.

Cancer therapy is rapidly evolving from a one-size-fits-all paradigm toward highly personalized approaches. Traditional chemotherapies and radiotherapies, while broadly applied, often yield suboptimal outcomes due to tumor heterogeneity and are limited by significant toxicities. In contrast, precision oncology tailors prevention, diagnosis, and treatment to the individual patient's genetic and molecular profile. Key advancements underscore this shift: molecularly targeted drugs (e.g., trastuzumab for HER2-positive breast cancer, EGFR and ALK inhibitors for lung cancer) have improved efficacy a

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… CarelonRx Fyarro (Sirolimus Albumin Bound)—Medical Drug Clinical Criteria Available online: https://www.carelonrx.com/ms/pharmacyinformation/Fyarro.pdf (accessed on 15 September 2025) 73. U.S. … Food and Drug Administration FDA Approves Sirolimus Protein-Bound Particles for Malignant Perivascular Epithelioid Cell Tumor Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sirolimus-protein-bound-particles-malignant-perivascular-epithelioid-cell-tumor ( …

Nanotherapeutics in the EU: an overview on current state and future directions.

The application of nanotechnology in areas of drug delivery and therapy (ie, nanotherapeutics) is envisioned to have a great impact on public health. The ability of nanotherapeutics to provide targeted drug delivery, improve drug solubility, extend drug half-life, improve a drug's therapeutic index, and reduce a drug's immunogenicity has resulted in the potential to revolutionize the treatment of many diseases. In this paper, we review the liposome-, nanocrystal-, virosome-, polymer therapeutic-, nanoemulsion-, and nanoparticle-based approaches to nanotherapeutics, which represent the most suc

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… Nanotechnology-based approach | Drug | Major indication | Dosage form | Brand name (Manufacturer * info source) | Marketing authorization in Europe ** Nanocrystals | Sirolimus | Graft rejection, Kidney transplantation | Tablet | Rapamune® (Pfizer Ireland Pharmaceuticals, Dublin, IE) | CP: -MAH: Pfizer … enabled its formulation in tablets (when compared to previously used liquid dosage form) reducing the dose needed which consequently diminished influence of drug content on the tableting process (ie, the tablet contains only 1–5 mg sirolimus in the tablet, weighing about 370 mg). 42 Tablets are a more …

Current and emerging therapeutic options in adrenocortical cancer treatment.

Adrenocortical carcinoma (ACC) is a very rare endocrine tumour, with variable prognosis, depending on tumour stage and time of diagnosis. The overall survival is five years from detection. Radical surgery is considered the therapy of choice in the first stages of ACC. However postoperative disease-free survival at 5 years is only around 30% and recurrence rates are frequent. o,p'DDD (ortho-, para'-, dichloro-, diphenyl-, dichloroethane, or mitotane), an adrenolytic drug with significant toxicity and unpredictable therapeutic response, is used in the treatment of ACC. Unfortunately, treatment f

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… The most important inhibitors of mTOR are rapamycin (sirolimus) and its derivatives everolimus (RAD001) and temsirolimus (CCI-779) [ 89 ]. … Nevertheless, in a recent study, Gangadhar et al. observed a partial response in a patient with ACC treated with sirolimus and sunitinib in combination [ 98 ]. …

Development and implementation of the International AIDA Network Castleman's disease registry.

Castleman's disease (CD) consists of a wide spectrum of rare disorders classified into unicentric CD and multicentric CD (MCD), based on the diffusion of disease distribution and the severity of clinical manifestations. While unicentric CD is characterized by a single lymph node involvement, MCD is defined by multiple lymph node station involvement with more prominent systemic symptoms. MCD is further subdivided into HHV-8 associated MCD, polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS)-associated MCD, and idiopathic MCD (iMCD), which is also

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… Alternative regimens, such as mTOR inhibitors (sirolimus), anti-IL1 agents (primarily anakinra), JAK inhibitors (ruxolitinib), proteasome inhibitors (bortezomib), lenalidomide/thalidomide, and cyclosporin A, are supported only by case series and reports ( 35–48 ). … Refractory idiopathic multicentric Castleman disease responsive to sirolimus therapy. Am J Hematol. (2023) 98:361–4. doi: 10.1002/ajh.26783, PMID: 36. Stern RM, Berliner N. Targeting the mTOR pathway in idiopathic multicentric Castleman disease. …

Cardiovascular mortality in liver and kidney transplant recipients: A retrospective analysis from a single institution.

AbstractPrevious studies have demonstrated cardiovascular causes to be among the leading causes of death after liver (LT) and kidney transplantation (KT). Although both recipient populations have unique pre-transplant cardiovascular burdens, they share similarities in post-transplant exposure to cardiovascular risk factors. The aim of this study was to compare cardiovascular mortality after LT and KT.We analyzed causes of death in 370 consecutive LT and 207 KT recipients from in-hospital records at a single tertiary transplant center. Cardiovascular causes of death were defined as cardiac arre

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… Sirolimus induced dyslipidemia in tacrolimus based vs. tacrolimus free immunosuppressive regimens in renal transplant recipients . Ann Transplant 2008 ; 13 : 46 – 53 . 18566560 [9] Trotter JF Wachs ME Trouillot TE . … Dyslipidemia during sirolimus therapy in liver transplant recipients occurs with concomitant cyclosporine but not tacrolimus . Liver Transplant 2001 ; 7 : 401 – 8 . 10.1053/jlts.2001.23916 11349259 [10] Glover TE Watson CJE Gibbs P . …

Influence and Role of Regulatory B Cells in Organ Transplantation: The State of the Art, Prospects, and Emerging Insights.

B cells have attracted increasing interest in the field of organ transplantation due to their newly discovered immunoregulatory properties in alloimmune responses. Traditionally, B cells have been primarily associated with adaptive immunity to foreign substances and alloreactive immune response to allografts, differentiating into antibody-producing plasma cells or memory cells upon antigen recognition and T cell collaboration. However, the existence of B cells with regulatory functions (Bregs) in humans has been widely confirmed, highlighting the presence of this subset, which has immunosuppre

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… Indirect results from other groups also suggest a role for Bregs in liver transplant tolerance and rejection, as an expansion of transitional B cells and Tregs was seen during the first month in patients converting from Tacrolimus to Sirolimus, a drug reported to induce long-term immunotolerance [ 67 … The advantage of Sirolimus in amplifying regulatory B cells and regulatory T cells in liver transplant patients Eur. J. Pharmacol. 2020 869 172872 10.1016/j.ejphar.2019.172872 31846626 68. Piloni D. Morosini M. Magni S. Balderacchi A. Inghilleri S. Cova E. Oggionni T. Frangipane V. Pandolfi L. …

Ceftazidime-Avibactam Regimens for the Treatment of Bacteremic and Non-Bacteremic Episodes of Carbapenemase-Producing Enterobacterales Infections in Immunosuppressed Patients.

Ceftazidime-avibactam (CA) and CA plus aztreonam (ATM) are the preferred treatment options for KPC and MBL carbapenemase-producing Enterobacterales infections (CPEis). All episodes of monomicrobial CPEis in immunosuppressed patients (IPs) admitted from May 2019 to November 2024, who received definitive antibiotic therapy (AT) with CA or CA + ATM for at least 72 h, were prospectively included. Bacteremic episodes (BEs) and non-bacteremic episodes (NBEs) were compared. Logistic regressions adjusted by propensity score were used to identify variables associated with 30-day overall mortality. In t

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… Immunosuppressive therapy was defined as the administration of one or more of the following drugs at the time of infection: cyclosporine, mycophenolate mofetil, tacrolimus, sirolimus, and methotrexate. Neutropenia was defined as an absolute neutrophil count <500 cells/mm 3 . … Other suppressors: ciclosporin, mycophenolate mofetil or sodium, tacrolimus, sirolimus, and methotrexate. …

mTORC1 hyperactivity inhibits serum deprivation-induced apoptosis via increased hexokinase II and GLUT1 expression, sustained Mcl-1 expression, and glycogen synthase kinase 3beta inhibition.

The current concept is that Tsc-deficient cells are sensitized to apoptosis due to the inhibition of Akt activity by the negative feedback mechanism induced by the hyperactive mTORC1. Unexpectedly, however, we found that Tsc1/2-deficient cells exhibit increased resistance to serum deprivation-induced apoptosis. mTORC1 hyperactivity contributes to the apoptotic resistance of serum-deprived Tsc1/2-deficient cells in part by increasing the growth factor-independent expression of hexokinase II (HKII) and GLUT1. mTORC1-mediated increase in hypoxia-inducible factor 1alpha (HIF1alpha) abundance, whic

The role of hypoxic microenvironment in autoimmune diseases.

The hypoxic microenvironment, characterized by significantly reduced oxygen levels within tissues, has emerged as a critical factor in the pathogenesis and progression of various autoimmune diseases (AIDs). Central to this process is the hypoxia-inducible factor-1 (HIF-1), which orchestrates a wide array of cellular responses under low oxygen conditions. This review delves into the multifaceted roles of the hypoxic microenvironment in modulating immune cell function, particularly highlighting its impact on immune activation, metabolic reprogramming, and angiogenesis. Specific focus is given to

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… In clinical application, sirolimus, an outstanding representative of mTOR inhibitors, is widely used to prevent rejection after solid organ transplantation and protect the safety of transplanted organs through its powerful immunosuppressive effect. … For AIDs such as primary immune thrombocytopenia (ITP), sirolimus elicits suppressive immunomodulatory actions by augmenting the Treg cell proportion within the helper T lymphocyte subset, bolstering the count of naive T cells, triggering apoptosis in memory T cells, diminishing effector T cells, and …

Novel Molecular Therapies and Genetic Landscape in Selected Rare Diseases with Hematologic Manifestations: A Review of the Literature.

Rare diseases affect less than 1 in 2000 people and are characterized by a serious, chronic, and progressive course. Among the described diseases, a mutation in a single gene caused mastocytosis, thrombotic thrombocytopenic purpura, Gaucher disease, and paroxysmal nocturnal hemoglobinuria (KIT, ADAMTS13, GBA1, and PIG-A genes, respectively). In Castleman disease, improper ETS1, PTPN6, TGFBR2, DNMT3A, and PDGFRB genes cause the appearance of symptoms. In histiocytosis, several mutation variants are described: BRAF, MAP2K1, MAP3K1, ARAF, ERBB3, NRAS, KRAS, PICK1, PIK3R2, and PIK3CA. Genes like H

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… Therapies targeting interleukin 6 (like tocilizumab) are highly effective in many iMCD patients, but other therapies (such as corticosteroids, rituximab, thalidomide, lenalidomide, bortezomib, cyclosporine, sirolimus, or interferon) are required in refractory cases [ 18 ]. … antihistamines, cromolyn sodium, corticosteroids, methoxypsoralen therapy with long-wave psoralen plus ultraviolet A, midostaurin, imatinib, nilotinib, dasatinib, masitinib, avapritinib, ripretinib, cladribine Castleman disease | corticosteroids, rituximab, thalidomide, lenalidomide, bortezomib, cyclosporine, sirolimus …

Metabolic Syndrome and Cardiovascular Disease after Hematopoietic Cell Transplantation: Screening and Preventive Practice Recommendations from the CIBMTR and EBMT.

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all-cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with an estimated prevalence of MetS of 31% to 49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and

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… In addition, immunosuppressant medications (e.g., sirolimus, calcineurin inhibitors, corticosteroids) not only increase lipid levels but also lead to significant drug-drug interactions with 3-hydroxy-3-methyl-gutaryl (HMG)-CoA reductase inhibitors (statins) via the cytochrome p450 pathway [ 50 , 51 ] … For high-risk patients with ongoing risk factors (including those on sirolimus, calcineurin inhibitors, corticosteroids), we suggest repeat evaluation every 3–6 months. In recipients without ongoing risk factors, we suggest repeat evaluation according recommendations for the general population. …

Совместное управление триазолами с хемапаевыми и/или иммунозопрессивными агентами, известными умеренным взаимодействием между наркотиками и наркотиками у пациентов с гематологическими заболеваниями, госпитализировано в связи с инвазивным аспергиллозом.

ОБРАЩЕНИЕ: Триазолы широко используются для лечения и профилактики инвазивного аспергиллоза (ИА), но могут вызывать серьезное взаимодействие с наркотиками (ДПИ) с химиотерапией (ХТ) и иммунодепрессантами (ИС) посредством ингибирования CYP3A4. Частота получения трехазол-ХТ или одновременного лечения в случае гематологовых заболеваний (ГМ) вновь принятых в ПА пациентов в целом неизвестна. Мы изучили американские претензии IQVIA, в том числе в отношении взрослых ≥ 1 требование о пребывании в стационаре с диагностическим кодом для АИ с октября 1, 2015- ноябрь 30, 2022 и доказательства существовани

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… Interactions in Patients with Hematologic Malignancies and Invasive Aspergillosis Chemotherapy or Immunosuppressant* N = 308 n (%) † At least one agent 241 (78.2) Corticosteroids 218 (70.8) Dexamethasone 153 (49.7) Methylprednisolone 133 (43.2) Calcineurin or mTOR inhibitors 77 (25.0) Tacrolimus 65 (21.1) Sirolimus … and/or immunosuppressant, so the column will not total to 100% Chemotherapy or Immunosuppressant* | N = 308 n (%) † At least one agent | 241 (78.2) Corticosteroids | 218 (70.8) Dexamethasone | 153 (49.7) Methylprednisolone | 133 (43.2) Calcineurin or mTOR inhibitors | 77 (25.0) Tacrolimus | 65 (21.1) Sirolimus …

Targeting Metabolic Reprogramming in Acute Myeloid Leukemia.

The cancer metabolic reprogramming allows the maintenance of tumor proliferation, expansion and survival by altering key bioenergetics, biosynthetic and redox functions to meet the higher demands of tumor cells. In addition, several metabolites are also needed to perform signaling functions that further promote tumor growth and progression. These metabolic alterations have been exploited in different cancers, including acute myeloid leukemia, as novel therapeutic strategies both in preclinical models and clinical trials. Here, we review the complexity of acute myeloid leukemia (AML) metabolism

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… . | Active, not recruiting Sirolimus | Azacitidine | NCT01869114 Phase II trial studies how well sirolimus and azacitidine works in treating patients with high-risk myelodysplastic syndrome or recurrent AML. | Recruiting Hydroxychloroquine (HCQ) | Mitoxantrone and Etoposide | NCT02631252 Phase I study … The interactions between mTORC1 and PI3K/AKT are complex, with mTORC1 exerting a negative control of PI3K/AKT that is alleviated upon mTORC1 inhibition by sirolimus [ 117 ]. A potential mechanism for PI3K activation in AML might implicate increased VEGF levels [ 48 ]. …

Current approach to the diagnosis and treatment of femoral-popliteal arterial disease. A systematic review.

Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis affecting 5 million adults in the United States, with an age-adjusted prevalence of 4% to 15% and increasing up to 30% with age and the presence of cardiovascular risk factors. In this article we focus on lower extremity PAD and specifically on the superficial femoral and proximal popliteal artery (SFPA), which are the most common anatomic locations of lower extremity atherosclerosis. We summarize current evidence and perform a systematic review on the diagnostic evaluation as well as the medical, endovascular and s

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… The SIROCCO II study, a randomized trial of sirolimus-coated nitinol stents compared to bare metal nitinol stents for SFPA disease, demonstrated no significant difference in patency rates. … At 24 months of follow-up, the restenosis rate in the sirolimus group was 22.9% versus 21.1% in the bare metal stent group [ 103 ]. …

Трансплантация стволовой клетки для высокой/ультра высокой степени риска с несколькими миеломами.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

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… Two patients had mild acute GVHD, while five patients experienced chronic grade I GVHD of the skin, liver, and bowel, which all improved and were stable with immunosuppressive therapy (including varying combinations of prednisone, tacrolimus, sirolimus, triamcinolone, rituximab, mycophenolate mofetil …

Targeting CD38 Across Autoimmune and Plasma Cell-Driven Immune-Mediated Diseases: Rationale, Clinical Evidence, and Emerging Therapeutic Landscape.

Autoimmune diseases remain a major cause of chronic morbidity despite substantial advances in targeted immunomodulatory therapies. In many autoantibody-mediated conditions, disease refractoriness and relapse are driven by long-lived plasma cells, which are largely resistant to conventional immunosuppression and upstream B cell-directed strategies. CD38, a surface molecule highly expressed on plasmablasts and plasma cells and functionally involved in immunometabolic regulation, has emerged as a promising therapeutic target to overcome this limitation. Clinical interest in anti-CD38 therapy has

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… MM-derived schedules) | 2 weeks | Hemoglobin improvement and clinical response after failure of B cell–directed strategies | Case report wAIHA post-HSCT for ALL [ 39 ] | 1 (19-year-old woman) | Steroids; rituximab (2 courses); high-dose cyclophosphamide; rabbit ATG; alemtuzumab; bortezomib (2 courses); MMF; sirolimus … ; ibrutinib | 16 mg/kg single infusion | 2–4 weeks | Marked reduction in red-cell transfusion requirement in a refractory patient | Case report wAIHA post-HSCT for ALL [ 40 ] | 3 (pediatric cases) | Steroids; rituximab; plasma exchange; bortezomib; MMF; sirolimus; ATG; cyclophosphamide; ibrutinib; eculizumab …

Взаимодействие между TH17 и центральной нервной системой в множестве склерозов.

Фото 1.

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… PI3K Novel azaindoles Inhibition of PI3K/AKT/mTOR pathway mTOR Sirolimus; Temsirolimus; Everolimus; CCR6 Anti-hCCR6 mAbs Inhibition of Th17 migration to CNS CB2 Gp1a Downregulation of RORγt, IL-1β, TNF-α, CCL2, CCL5, CXCL10, VCAM-1 and iNOS Table 2 Drugs targeting Th17-related cytokines and signaling … PI3K Novel azaindoles Inhibition of PI3K/AKT/mTOR pathway mTOR Sirolimus; Temsirolimus; Everolimus; CCR6 Anti-hCCR6 mAbs Inhibition of Th17 migration to CNS CB2 Gp1a Downregulation of RORγt, IL-1β, TNF-α, CCL2, CCL5, CXCL10, VCAM-1 and iNOS Drugs targeting Th17-related cytokines and signaling pathways …

Acute kidney injury in the patient with cancer.

Dramatic advances in the care of patients with cancer have led to significant improvement in outcomes and survival. However, renal manifestations of the underlying cancer as well as the effects of anti-neoplastic therapies leave patients with significant morbidity and chronic kidney disease risks. The most common renal manifestations associated with cancer include acute kidney injury (AKI) in the setting of multiple myeloma, tumor lysis syndrome, post-hematopoietic stem cell therapy, and AKI associated with chemotherapy. Knowledge of specific risk factors, modification of risk and careful atte

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… In addition to supportive measures, treatment of GVHD includes use of prednisone, antithymocyte globulin, sirolimus, and mycophenolate mofetil [ 88 ]. Tumor lysis syndrome TLS is a medical emergency and a common cause of cancer-induced AKI [ 89 ]. … 00004 19228075 74 Kennedy GA Kearey N Bleakley S Butler J Mudie K Durrant S Transplantation-associated thrombotic micro-angiopathy: effect of concomitant GVHD on efficacy of therapeutic plasma exchange Bone Marrow Transplant 2010 45 699 704 10.1038/bmt.2009.233 19767787 75 Cutler C Henry NL Magee C Sirolimus …

Multiple cystic lung disease.

Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main dise

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… The mTOR inhibitor sirolimus (rapamycin) appears to be the most effective drug in this treatment approach [ 39 ]. Treatment with sirolimus can stop the decline in lung function and improve quality of life [ 34 , 40 ]. …

The role and novel use of natural killer cells in graft-versus-leukemia reactions after allogeneic transplantation.

Allogeneic hematopoietic cell transplantation (HCT) has transformed over the past several decades through enhanced supportive care, reduced intensity conditioning (RIC), improved human leukocyte antigen (HLA) typing, and novel graft-versus-host disease (GVHD)-prevention and treatment strategies. Most notably, the implementation of post-transplantation cyclophosphamide (PTCy) has dramatically increased the safety and availability of this life-saving therapy. Given reductions in nonrelapse mortality (NRM) with these advances, the HCT community has placed even greater emphasis on developing ways

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… In the peri-HCT setting, strategies include optimization of graft cell dose, use of sirolimus rather than tacrolimus in post-HCT immunosuppression, and early and/or rapid immunosuppression taper ( 15 – 17 ). … Comparison of Tacrolimus and Sirolimus (Tac/Sir) versus Tacrolimus, Sirolimus, and mini-methotrexate (Tac/Sir/MTX) as acute graft-versus-host disease prophylaxis after reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation . …