Результаты поиска

Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update.

In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biolo

Advances in antisense oligonucleotide treatment for cancer.

RNA therapeutics, including antisense oligonucleotides (ASOs), have emerged as a promising class of drugs, with several already approved for clinical use. To date, most approved ASO-based RNA therapies target non-malignant disorders such as neurodegenerative diseases, and only a single therapy in this class has been approved for cancer. Notably, nearly half of existing RNA therapeutics act by modulating RNA splicing. Given the growing evidence implicating aberrant RNA splicing in cancer pathogenesis, the development of ASO-based therapeutics for oncologic indications is expected to accelerate.

A case of IgE myeloma transformed into IgE-producing plasma cell leukaemia.

This is a case report of a challenging diagnosis of IgE monoclonal gammopathy of undetermined significance, which transformed into myeloma, then transformed into IgE-producing plasma cell leukaemia in a 71-year-old male who was followed in Brest, France, from 2015 to 2019. The IgE-producing variant is the rarest sub-type of multiple myeloma, and plasma cell leukaemia is considered to be the rarest and the most aggressive of human monoclonal gammopathies. In November 2015, hypogammaglobulinemia was detected during a systematic check-up. A kappa light chain monoclonal gammopathy was first diagno

Novel therapies emerging in oncology to target the TGF-β pathway.

The TGF-β signaling pathway governs key cellular processes under physiologic conditions and is deregulated in many pathologies, including cancer. TGF-β is a multifunctional cytokine that acts in a cell- and context-dependent manner as a tumor promoter or tumor suppressor. As a tumor promoter, the TGF-β pathway enhances cell proliferation, migratory invasion, metastatic spread within the tumor microenvironment and suppresses immunosurveillance. Collectively, the pleiotropic nature of TGF-β signaling contributes to drug resistance, tumor escape and undermines clinical response to therapy. Based

Comprehensive Updates in the Role of Imaging for Multiple Myeloma Management Based on Recent International Guidelines.

The diagnostic and treatment methods of multiple myeloma (MM) have been rapidly evolving owing to advances in imaging techniques and new therapeutic agents. Imaging has begun to play an important role in the management of MM, and international guidelines are frequently updated. Since the publication of 2015 International Myeloma Working Group (IMWG) criteria for the diagnosis of MM, whole-body magnetic resonance imaging (MRI) or low-dose whole-body computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography/CT have entered the mainstream as diagnostic and treatment respons

Management of Multiple Myeloma: A Review for General Practitioners in Oncology.

Multiple myeloma (MM) is a malignant clonal plasma cell disorder in the bone marrow and is the second-most common hematologic malignancy in adults. Although patients with MM have a moderate life expectancy, it remains a heterogeneous disease that often requires multiple lines of chemotherapy for durable control and long-term survival. This review outlines current management strategies for both transplant-eligible and transplant-ineligible patients as well as for relapsed and refractory disease. Advances in drug therapies have widened management options and improved survival. In this paper, we

Beta-blockers and glioma: a systematic review of preclinical studies and clinical results.

Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and prolifer

A Pathology Experience of Posttransplant Lymphoproliferative Disorder From One Tertiary Hospital: Pathology Concepts and Diagnostic Approach.

BACKGROUND: Solid organ transplantation and bone marrow/hematologic stem cell transplantation recipients face a heightened risk of developing malignancies or cancer as a result of immunosuppression. Posttransplant lymphoproliferative disorders (PTLD) are a range of disorders from benign lymphoid growth to lymphoma found post-transplant. Risk factors for PTLD include high immunosuppressive use and oncogenic effects of Epstein-Barr virus (EBV). There is a lack of comprehensive clinical and pathological documentation of PTLD cases among Saudi patients, and the available data are limited to a few

Acute Myeloid Leukaemia in Its Niche: the Bone Marrow Microenvironment in Acute Myeloid Leukaemia.

Purpose of reviewAcute myeloid leukaemia (AML) is a heterogeneous malignancy for which treatment options remain suboptimal. It is clear that a greater understanding of the biology of the AML niche will enable new therapeutic strategies to be developed in order to improve treatment outcomes for patients.Recent findingsRecent evidence has highlighted the importance of the bone marrow microenvironment in protecting leukaemia cells, and in particular leukaemic stem cells from chemotherapy-induced cell death. This includes mesenchymal stem cells supporting growth and preventing apoptosis, and alter

The expression and role of miR-181a in multiple myeloma.

This study aims to investigate the role of miR-181a in multiple myeloma (MM). Fresh peripheral blood and bone marrows were collected. Expression of miR-181a, BCL-2 mRNA, and NOVA1 mRNA was detected by RT-qPCR. The correlation between miR-181a and clinical features of MM was further analyzed. miR-181a in serum and bone marrow mononuclear cells of MM patients were significantly higher. And, miR-181a level was significantly higher in MM Durie-Salmon stage III than that in stage I+II. miR-181a was positively correlated to Durie-Salmon staging, age, kidney injury, bone injury, β2-MG whereas negativ

The Role of TAM Receptors in Bone.

The TAM (TYRO3, MERTK, and AXL) family of receptor tyrosine kinases are pleiotropic regulators of adult tissue homeostasis maintaining organ integrity and self-renewal. Disruption of their homeostatic balance fosters pathological conditions like autoinflammatory or degenerative diseases including rheumatoid arthritis, lupus erythematodes, or liver fibrosis. Moreover, TAM receptors exhibit prominent cell-transforming properties, promoting tumor progression, metastasis, and therapy resistance in various cancer entities. Emerging evidence shows that TAM receptors are involved in bone homeostasis

Efficacy and safety of CD38-directed CAR-T cell therapy for multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: Relapsed/refractory multiple myeloma (RRMM) remains a clinical challenge despite therapeutic advances. CD38-directed chimeric antigen receptor T-cell (CAR-T) therapy, especially dual-target CD38/BCMA constructs, represents an emerging immunotherapeutic strategy. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD38-directed CAR-T in RRMM. METHODS: We systematically searched Medline, Embase, and Cochrane Library up to October 1, 2025. Eligible clinical trials investigating CD38-directed CAR-T (single-target or dual-target CD38/BCMA) for RRMM wer

First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro.

OBJECTIVES: The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. METHODS: Twenty newly diagnosed patients received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also st

Совпадение в полном тексте источника
… Differential effects of transforming growth factor beta2, dexamethasone and 1,25-dihydroxyvitamin D on human bone marrow stromal cells. Cytokine. 1997;9:613–23. doi: 10.1006/cyto.1997.0209. 47. Pereira RC, Delany AM, Canalis E. …

Circadian rhythm-guided cellular therapy in hematologic malignancies: mechanisms, clinical evidence, and optimization strategies.

Circadian rhythms are endogenous 24-hour timing systems that coordinate hematopoiesis and immune function through central and peripheral clocks. Increasing evidence indicates that the initiation and progression of hematologic malignancies are frequently accompanied by circadian disruption, which not only contributes to malignant transformation and disease progression but also anti-tumor immunity and variable treatment responses. Cellular therapies, particularly hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor T-cell therapy (CAR-T), have emerged as transformative mo

Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells.

Cancer recurrence remains a great fear for many cancer survivors following their initial, apparently successful, therapy. Despite significant improvement in the overall survival of many types of cancer, metastasis accounts for ~90% of all cancer mortality. There is a growing understanding that future therapeutic practices must accommodate this unmet medical need in preventing metastatic recurrence. Accumulating evidence supports dormant disseminated tumor cells (DTCs) as a source of cancer recurrence and recognizes the need for novel strategies to target these tumor cells. This review presents

Natural killer T cells subsets in cancer, functional defects in prostate cancer and implications for immunotherapy.

Natural killer T cells are T lymphocytes with unique activation and effector properties. The majority of NKT cells, termed type-I or iNKT cells, recognize lipid antigens presented on MHC-like CD1d molecules. Type-I NKT cells have the capacity to rapidly secrete various cytokines upon activation, thereby regulate immune responses exerts dominant anti-tumor and anti-microbial effector functions. Specific activation of type-I NKT cells in mouse models boosts immunity and prevents metastasis, which has led to a number of phase I-II clinical trials. Since the discovery of NKT cells other subsets wi

Molecular and cellular mechanisms of skeletal muscle atrophy: an update.

Skeletal muscle atrophy is defined as a decrease in muscle mass and it occurs when protein degradation exceeds protein synthesis. Potential triggers of muscle wasting are long-term immobilization, malnutrition, severe burns, aging as well as various serious and often chronic diseases, such as chronic heart failure, obstructive lung disease, renal failure, AIDS, sepsis, immune disorders, cancer, and dystrophies. Interestingly, a cooperation between several pathophysiological factors, including inappropriately adapted anabolic (e.g., growth hormone, insulin-like growth factor 1) and catabolic pr

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.

Transforming growth factor-beta (TGF-β) signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate) is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically

Perspectives on interferon-alpha in the treatment of polycythemia vera and related myeloproliferative neoplasms: minimal residual disease and cure?

The first clinical trials of the safety and efficacy of interferon-alpha2 (IFN-alpha2) were performed about 30 years ago. Since then, several single-arm studies have convincingly demonstrated that IFN-alpha2 is a highly potent anti-cancer agent in several cancer types but unfortunately not being explored sufficiently due to a high toxicity profile when using non-pegylated IFN-alpha2 or high dosages or due to competitive drugs, that for clinicians at first glance might look more attractive. Within the hematological malignancies, IFN-alpha2 has only recently been revived in patients with the Phi

Next Generation Therapeutics for the Treatment of Myelofibrosis.

Myelofibrosis is a myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, bone marrow fibrosis, and a propensity towards transformation to acute leukemia. JAK inhibitors are the only approved therapy for myelofibrosis and have been successful in reducing spleen and symptom burden. However, they do not significantly impact disease progression and many patients are ineligible due to coexisting cytopenias. Patients who are refractory to JAK inhibition also have a dismal survival. Therefore, non-JAK inhibitor-based therapies are being explored in pre-clinical and clini