1,720,982 research outputs found
The bone marrow niche landscape: a journey through aging, extrinsic and intrinsic stressors in the haemopoietic milieu
Get PDFInflammation and its effects in the bone marrow microenvironment represent a paradigmatic condition in which the hematopoietic niche and the immune systems, thought to properly sustain blood cell production and distinguish between friend and foe, can actively sustain a corrupted neighborhood within a chronic aberrant inflamed state. The bone marrow niche hijacks the physiologic hematopoiesis. The interactions between the hematopoietic stem cells and the niche in the bone marrow are critical determinants of quiescence. We examined several approaches to confront the available evidence; three key points emerged, pointing to the chronic inflammation process, especially the chronic infection and systemic inflammatory states, as leading causes of hematopoietic stem cell depletion. Clonal hematopoiesis, defined as a relative expansion of individual clones, is caused by somatic alterations in essential hematopoietic genes, which increase stem cell fitness. Moreover, terminal differentiation plays a significant role in progenitor loss and inflammatory signaling, promoting clonal selection and clonal hematopoiesis conditions. Specific myeloid malignancies as paradigmatic examples are discussed as a condition associated with inflammation, including the 5q- syndrome, Philadelphia negative myeloproliferative neoplasms, and chronic myeloid leukemia. Aging with increased fitness and hematopoietic stem cell attrition, extrinsic stress, enhanced stressor-specific fitness, and intrinsic defect across the hematopoietic process represent the route for novel insights in defective hematopoiesis. The discussion in this review also points out that the hematopoietic niches’ inflammatory stimulation may affect differentiation patterns and the function of downstream cells
Anti-VEGF Drugs in the Treatment of Multiple Myeloma Patients
Get PDFThe interaction between the bone marrow microenvironment and plasma cells plays an essential role in multiple myeloma progression and drug resistance. The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway in vascular endothelial cells activates and promotes angiogenesis. Moreover, VEGF activates and promotes vasculogenesis and vasculogenic mimicry when it interacts with VEGF receptors expressed in precursor cells and inflammatory cells, respectively. In myeloma bone marrow, VEGF and VEGF receptor expression are upregulated and hyperactive in the stromal and tumor cells. It has been demonstrated that several antiangiogenic agents can effectively target VEGF-related pathways in the preclinical phase. However, they are not successful in treating multiple myeloma, probably due to the vicarious action of other cytokines and signaling pathways. Thus, the simultaneous blocking of multiple cytokine pathways, including the VEGF/VEGFR pathway, may represent a valid strategy to treat multiple myeloma. This review aims to summarize recent advances in understanding the role of the VEGF/VEGFR pathway in multiple myeloma, and mainly focuses on the transcription pathway and on strategies that target this pathway
Real-life experience with omalizumab in chronic spontaneous urticaria.
No full textChronic spontaneous urticaria (CSU) is a common skin disease. Many patients with CSU do not have a response to therapy with H1 antihistamines, even at high dose. Evidence has shown that omalizumab, a recombinant
humanized monoclonal antibody approved as add-on therapy for persistent allergic asthma, is highly effective fot the treatment of CSU. We gave
omalizumab at dose of 300 mg once a month for 24 weeks to three patients, with moderate to severe CSU, that were refractory to standard treatment, including high doses of antihistamines, corticosteroid and cyclosporine.
This treatment period was followed by a maintenance period. There was dramatic improvement in the primary efficacy variable, the change in mean urticaria activity score (UAS) from baseline to the final week of omalizumab treatment. There was an improvement in quality of life, interference with daily activities and with sleep. Omalizumab diminished clinical symptoms and signs of CSU in patients who remained symptomatic despite standard therapy (licensed doses). The mechanism by which omalizumab works to improve urticaria has not been fully elucidated
Peculiar presentation of skin lymphoma could be missdiagnosed as sarcoidosis: a case report.
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Difficult therapeutic choices in a patient suffering from severe scleroderma and colon adenocarcinoma.
No full textEfficacy of filgrastim, lenograstim and peg-filgrastim in the mobilization of peripheral blood progenitor cells in patients with lymphoproliferative disorders.
No full textAngiogenesis and Antiangiogenesis in Multiple Myeloma
Get PDFMultiple myeloma progression is characterized by a dense interaction between cancer cells and bone marrow microenvironment. The interactions of myeloma cells with various stromal cells and extracellular matrix components are the main regulator of the biological processes that underlie the progression of the disease and of the classic symptomatology correlated. The bone marrow of myeloma patients has recognized autocrine and paracrine loops that regulate multiple signaling pathways and the malignant phenotype of plasma cells. One of the pivotal biological processes which are responsible for myeloma progression is the formation of new vessels from existing ones, known as angiogenesis. It represents a constant hallmark of disease progression and a characteristic feature of the active phase of the disease. Near angiogenesis, other two ancestral processes were active in the bone marrow: vasculogenesis and vasculogenic mimicry. These processes are mediated by the angiogenic cytokines, interleukins, and inflammatory cytokines directly secreted by plasma cells and stromal cells. Neovascularization is also mediated by direct interaction between plasma cells and the various components of bone marrow microenvironment. The observation of the increased bone marrow angiogenesis in multiple myeloma and its correlation with disease activity and overall survival led to consider angiogenesis as a new target in the treatment of multiple myeloma
Functional and biological role of endothelial precursor cells in tumour progression: A new potential therapeutic target in haematological malignancies
Get PDFIt was believed that vasculogenesis occurred only during embryo life and that postnatal formation of vessels arose from angiogenesis. Recent findings demonstrate the existence of Endothelial Precursor Cells (EPCs), which take partin postnatal vasculogenesis. EPCs are recruited from the bone marrow under the stimulation of growth factors and cytokines and reach the sites of neovascularization in both physiological and pathological conditions such as malignancies where they contribute to the "angiogenic switch" and tumor progression. An implementation of circulating EPCs in the bloodstream of patients with haematological malignancies has been demonstrated. This increase is strictly related to the bone marrow microvessel density and correlated with a poor prognosis. The EPCs characterization is a very complex process and still under investigation. This literature review aims to provide an overview of the functional and biological role of EPCs in haematological malignancies and to investigate their potential as a new cancer therapeutic target
Thrombopoietin promotes angiogenesis and disease progression in patients with multiple myeloma
Get PDFMultiple myeloma (MM) progression closely depends on bone marrow (BM) angiogenesis. Several factors sustain angiogenesis including cytokines, growth factors, and cell-to-cell interactions. Here, we found that BM thrombopoietin (TPO) supports angiogenesis and disease progression in MM. Patients with MM at different progression phases have higher levels of BM and circulating TPO than MGUS/smouldering MM patients, suggesting that TPO correlates with disease progression and prognosis. Endothelial cells from MGUS (MGECs) and MM (MMECs) patients express TPO receptor, and the TPO treatment triggers their angiogenic capabilities in vitro. Indeed, TPO-treated MGECs and MMECs show enhanced angiogenesis on Matrigel and spontaneous cell migration and chemotaxis by acting as a chemotactic agent. TPO also has an angiogenic activity in vivo in the CAM assay system. Finally, TPO treatment increases the release of active MMP-9 and MMP-2 in MGECs and of MMP-2 in MMECs and affects the balance between angiogenic/anti-angiogenic factors in the MM BM. Our results support the angiogenic activity of TPO, and suggest that it may have a critical role in promoting the angiogenic switch during MM progression. Accordingly, TPO may be envisaged as a new angiogenic and prognostic factor in MM patients
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