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Modulation of Angiogenic Processes by the Human Gammaherpesviruses, Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus.

Angiogenesis is the biological process by which new blood vessels are formed from pre-existing vessels. It is considered one of the classic hallmarks of cancer, as pathological angiogenesis provides oxygen and essential nutrients to growing tumors. Two of the seven known human oncoviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), belong to the Gammaherpesvirinae subfamily. Both viruses are associated with several malignancies including lymphomas, nasopharyngeal carcinomas, and Kaposi's sarcoma. The viral genomes code for a plethora of viral factors, includin

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… For example, the switch of immunosuppressant from cyclosporin A to the mTOR inhibitor rapamycin (Sirolimus) elicited KS regression in transplant patients, and it is now the first line of treatment for transplant KS ( Stallone et al., 2005 ). …

Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.

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… cell lung cancer did not improve survival compared to what would have been expected without nitroglycerin. 9 | Advanced bone cancer treatment with a combination of chemotherapy and immunosuppressants | A phase Ib study of metronomic cyclophosphamide and methotrexate combined with zoledronic acid and sirolimus … in patients with solid tumors with bone metastasis and advanced pretreated osteosarcoma (Metzolimos). | Solid tumors Bone cancer | 1 b | Completed | The dose of sirolimus that can be safely administered in combination with the 3 other drugs was determined. 10 | Combination of 9 repurposed drugs with …

Therapies for Chronic Allograft Rejection.

Remarkable advances have been made in the pathophysiology, diagnosis, and treatment of antibody-mediated rejection (ABMR) over the past decades, leading to improved graft outcomes. However, long-term failure is still high and effective treatment for chronic ABMR, an important cause of graft failure, has not yet been identified. Chronic ABMR has a relatively different phenotype from active ABMR and is a slowly progressive disease in which graft injury is mainly caused by de novo donor specific antibodies (DSA). Since most trials of current immunosuppressive therapies for rejection have focused

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… Sirolimus, an mTOR inhibitor, may suppress the number of circulating Tfh cells more efficiently than tacrolimus, but sirolimus is more likely to be associated with the development of dnDSA development than tacrolimus ( Laguna-Goya et al., 2019 ). …

New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions.

Chronic graft-versus-host disease (cGvHD) is a severe complication of allogeneic hematopoietic stem cell transplantation that affects various organs leading to a reduced quality of life. The condition often requires enduring immunosuppressive therapy, which can also lead to the development of severe side effects. Several approaches including small molecule inhibitors, antibodies, cytokines, and cellular therapies are now being developed for the treatment of cGvHD, and some of these therapies have been or are currently tested in clinical trials. In this review, we discuss these emerging therapi

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… In a series of 28 patients, begelomab was administered at 2–4.5 mg/day for 5 days, with possible 6 additional doses in 3 weeks, and this cohort was compared with 82 matched controls who received anti-thymocyte globulin, ECP, mycophenolate, sirolimus, etanercept, high dose cyclophosphamide. … In 2008, alemtuzumab was reported for the first time as an effective agent in a patient with extensive cutaneous cGvHD, who was already treated unsuccessfully with steroids, cyclosporine-A, sirolimus, tacrolimus, mychophenolate mofetil, infliximab, and rituximab. …

The updated landscape of tumor microenvironment and drug repurposing.

Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Cancer research and treatment have switched from a cancer-centric model to a TME-centric one, considering the increasing significance of TME in cancer biology. Nonetheless, the clinical efficacy of therapeutic strategies targeting TME, especially the specific cells or pathways of TME, remains unsatisfactory. Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly b

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… audio intervention Cervical cancer NCT01902966 Active, not recruiting Metformin Immunotherapy (nivolumab, pembrolizumab, sintilimab) NSCLC, SCLC, melanoma, solid tumors NCT03048500 ; NCT03311308 ; NCT03874000 ; NCT03874000 Recruiting NCT02145559 Completed Targeted therapy (temsirolimus, vandetanib, sirolimus … intervention | Cervical cancer | NCT01902966 | Active, not recruiting Metformin | Immunotherapy (nivolumab, pembrolizumab, sintilimab) | NSCLC, SCLC, melanoma, solid tumors | NCT03048500 ; NCT03311308 ; NCT03874000 ; NCT03874000 | Recruiting NCT02145559 | Completed Targeted therapy (temsirolimus, vandetanib, sirolimus …

Interplay of non-coding RNAs and approved antimetabolites such as gemcitabine and pemetrexed in mesothelioma.

Gemcitabine and pemetrexed are clinically approved antimetabolites for the therapy of mesothelioma diseases. These drugs are often applied in combination with platinum complexes and other drugs. The activity of antimetabolites depended on the expression levels of certain non-coding RNAs, in particular, of small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The development of tumor resistance towards antimetabolites was regulated by non-coding RNAs. An overview of the interplay between gemcitabine/pemetrexed antimetabolites and non-coding RNAs in mesothelioma is provided. Further to th

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… In human osteosarcoma cells, increased miR-34b expression caused by treatment with the mTOR-inhibitor sirolimus led to increased gemcitabine activity [ 49 ]. The tumor suppressor miR-143 is distinctly suppressed in MPM patients as to analyses of resected and biopsy samples [ 50 ]. … Sirolimus induces apoptosis and reverses multidrug resistance in human osteosarcoma cells in vitro via increasing microRNA-34b expression Acta Pharm. Sin. 37 2016 519 529 10.1038/aps.2015.153 PMC4820798 26924291 50 Andersen M. Grauslund M. Ravn J. Sorensen J.B. Andersen C.B. Santoni-Rugiu E. …

Risk factors and current state of therapy for anemia after kidney transplantation.

Post-transplant anemia is one of the most common complications in kidney transplant recipients, severely affecting patient prognosis and quality of life, and is an independent predictor of graft kidney loss and patient mortality. However, our clinical understanding and the attention given to post-transplant anemia are currently insufficient. This paper reviews the current status, risk factors, and therapeutic progress in anemia after transplantation in kidney transplant recipients. We recommend that clinical staff pay attention to anemia and its complications in kidney transplant recipients an

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… Anemia has been reported to be more common in patients taking MMF and sirolimus ( 12 ). Some studies have shown no relationship between anemia and immunosuppression, which may be due to the already poorer function of the transplanted kidney in such patients ( 30 ). …

Risk factors and outcome of COVID-19 in patients with hematological malignancies.

BackgroundPrognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined.Patients and methodsThis was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020.ResultsWe included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65

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… to COVID-19, days (range) | | 790 (10–10661) | 441 (6–7597) | 0.1 Prior therapy/conditioning 40 days before COVID-19, n (%) | 102 (42) | 24 (41) | 10 (15) | < 0.0001 Disease diagnosed within 40 days of COVID-19, n (%) | 60 (25) | 0 | 0 | < 0.0001 Under immunosuppressive drugs before COVID-19 CNI or sirolimus …

Ход работы сессии 31st Европейский педиатрический конгресс по педиатрии: часть 1.

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Treatment of acute kidney injury in cancer patients.

Acute kidney injury (AKI), either of pre-renal, renal or post-renal origin, is an important complication in cancer patients, resulting in worse prognosis, withdrawal from effective oncological treatments, longer hospitalizations and increased costs. The aim of this article is to provide a literature review of general and cause-specific treatment strategies for AKI, providing a helpful guide for clinical practice. We propose to classify AKI as patient-related, cancer-related and treatment-related in order to optimize therapeutic interventions. In the setting of patient-related causes, proper as

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… bortezomib, carfilzomib) | Underlying cause is not known; may respond to complement inhibition or plasmapheresis Pentostatine | Dose-dependent toxicity EGFR inhibitor (e.g. cetuximab, gefitinib, erlotinib) | Renal TMA Calcineurin inhibitor (e.g. ciclosporin, tacrolimus) | Renal TMA mTOR inibitors (e.g. sirolimus …

Bone Marrow versus Peripheral Blood Grafts for Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide.

In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patient

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… Patients with SR-aGVHD required second-line treatment with therapies including extracorporeal photopheresis, ruxolitinib, tacrolimus, sirolimus, vedolizumab, and infliximab. …

The Circular Life of Human CD38: From Basic Science to Clinics and Back.

Monoclonal antibodies (mAbs) were initially considered as a possible "magic bullet" for in vivo elimination of tumor cells. mAbs represented the first step: however, as they were murine in nature (the earliest experience on the field), they were considered unfit for human applications. This prompted the development of techniques for cloning the variable regions of conventional murine antibodies, genetically mounted on human IgG. The last step in this years-long process was the design for the preparation of fully human reagents. The choice of the target molecule was also problematic, since canc

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… In such setting, DARA showed encouraging results also as a rescue therapy in pre-treated patients refractory to common drugs such as rituximab, alemtuzumab, bortezomib, mycophenolate mofetil (MMF), sirolimus, and ibrutinib [ 68 ]. …

Serial low doses of sorafenib enhance therapeutic efficacy of adoptive T cell therapy in a murine model by improving tumor microenvironment.

Requirements of large numbers of transferred T cells and various immunosuppressive factors and cells in the tumor microenvironment limit the applications of adoptive T cells therapy (ACT) in clinic. Accumulating evidences show that chemotherapeutic drugs could act as immune supportive instead of immunosuppressive agents when proper dosage is used, and combined with immunotherapy often results in better treatment outcomes than monotherapy. Controversial immunomodulation effects of sorafenib, a multi-kinases inhibitor, at high and low doses have been reported in several types of cancer. However,

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… Int J Cancer 129 : 507 – 512 . 20839259 10.1002/ijc.25674 15 Molhoek KR , McSkimming CC , Olson WC , Brautigan DL , Slingluff Jr CL ( 2009 ) Apoptosis of CD4+CD25high T cells in response to Sirolimus requires activation of T Cell Receptor and is modulated by IL-2 . …

Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape for hematologic malignancies. However, it is frequently complicated by immune effector cell-associated hematotoxicity (ICAHT), a potentially life-threatening adverse event encompassing neutropenia, anemia, and thrombocytopenia. These cytopenias elevate the risk of severe infections, transfusion dependence, and prolonged hospital stays, contributing substantially to morbidity and non-relapse mortality. This review delineates the incidence, mechanisms, and risk factors for ICAHT, highlighting the complex inter

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… Case report: sirolimus alleviates persistent cytopenia after CD19 CAR-T-cell therapy. Front Oncol. 2021;11:798352. Associated Data Supplementary Materials Data Availability Statement The data on which this review is based are available upon request. …

Lenalidomide-associated B-cell ALL: clinical and pathologic correlates and sensitivity to lenalidomide withdrawal.

Lenalidomide is an effective component of induction and maintenance therapy for multiple myeloma, though with a risk of secondary malignancies, including acute lymphoblastic leukemia (ALL). In contrast to therapy-related myeloid neoplasia, lenalidomide-associated lymphoblastic neoplasia remains poorly characterized. We conducted a dual institution retrospective study of 32 ALL cases that arose after lenalidomide maintenance (all B-lineage, 31/32 BCR::ABL-negative). B-cell ALL (B-ALL) was diagnosed at median 54 months (range, 5-119) after first exposure to lenalidomide and after median 42 month

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… Graft-versus-host disease prophylaxis was calcineurin inhibitor–based for all HLA-matched donor recipients, whereas posttransplant cyclophosphamide with mycophenolate mofetil and either sirolimus (n = 1) or tacrolimus (n = 2) was used for HLA-mismatched related or unrelated donor recipients. …

Managing allorejection in off-the-shelf CAR-engineered cell therapies.

Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has revolutionized the treatment of various diseases, including cancers and autoimmune disorders. However, all US Food and Drug Administration (FDA)-approved CAR-T cell therapies are autologous, and their widespread clinical application is limited by several challenges, such as complex individualized manufacturing, high costs, and the need for patient-specific selection. Allogeneic off-the-shelf CAR-engineered cell therapy offers promising potential due to its immediate availability, consistent quality, potency, and scalability

Hyposalivation and salivary gland histopathology in graft-versus-host disease.

IntroductionA major long-term complication following allogeneic hematopoietic cell transplantation (HCT) is graft-versus-host disease (GVHD). Oral chronic GVHD (cGVHD) is common and affects the mucosa with diagnostic lichenoid-like manifestations. Distinctive features such as hyposalivation and inflammatory histopathology of the salivary glands have been associated with both transplant regimen and GVHD. We retrospectively explored the association of hyposalivation and minor salivary gland (MSG) histopathology with the establishment and progression of GVHD.MethodsA total of 791 patient records

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… HCT, hematopoietic cell transplantation; MDS, myelodysplastic syndrome; MPS, myeloproliferative syndrome; MF, Myelofibrosis; Metab, metabolic disorders; TBI, Total body irradiation; Cy, Cytoxan; CsA, cyclosporine A; MTX, methotrexate; Tac, tacrolimus; Sir, sirolimus; TcD, T-cell depletion; BM, bone marrow …

Identification of Potentially Pathogenic Variants Associated with Recurrence in Medication-Related Osteonecrosis of the Jaw (MRONJ) Patients Using Whole-Exome Sequencing.

Background: Bisphosphonates are antiresorptive and antiangiogenic drugs that prevent and treat bone loss and mineralization in women with postmenopausal osteoporosis and cancer patients. Medication-related osteonecrosis of the jaw (MRONJ) is commonly caused by tooth extraction and dental trauma. Although genetic and pathological studies about MRONJ have been conducted, the pathogenesis of MRONJ still remains unclear. Methods: We aimed to identify genetic variants associated with MRONJ, using whole-exome sequencing (WES). Ten MRONJ patients prescribed bisphosphonates were recruited for WES, and

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… The antiangiogenic agents or targets of the VEGF pathway, such as the anti-VEGF monoclonal antibodies (Bevacizumab) and tyrosine kinase inhibitors (Sunitinib, Sorafenib), that are prescribed for the treatment of cancer-related conditions or organ rejection in renal transplant patients (Sirolimus) have …

Pilot study of lithium to restore intestinal barrier function in severe graft-versus-host disease.

UNLABELLED: Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregula

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… MMF (or enteric coated mycophenolic acid) and sirolimus were often used in this setting. Agents with a high toxicity profile or poorly defined efficacy profile were reserved for severe GVHD considered to be refractory or unlikely to respond to standard measures. …

Glioma drug development benefits from emerging phase 0 and window-of-opportunity trial paradigm.

Clinical drug development is fundamentally difficult for rare and difficult-to-treat solid tumors, for example, glioma. Glioblastoma (GBM), an invariably fatal primary brain tumor, poses a significant challenge in the realm of effective treatments, necessitating an accelerated approach to innovative drug discovery. Investigators keep requiring a process toward obtaining more reliable early-stage signals related to drug activity and a process toward translating those signals into clinical benefits efficiently in late-stage drug development. Besides, these processes could increase the likelihood

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… activity | To evaluate MGMT activity | Role of carmustine to inhibit MGMT | NA | [ 67 ] Kuhn et al., 2007 | finished | recurrent glioma ( n = 6) | Temsirolimus | 170–250 mg | 1 dose 2 h before final resection | Blood, tumor | LC-MS/MS, blood and tumor drug concentration | Temsirolimus is an ester of sirolimus …