Search results for "topoi"
showing 10 items of 701 documents
Recent Advances in the Treatment of Patients with Multiple Myeloma
2020
Simple Summary The evolving data from trials assessing novel combinations as a part of the frontline and relapse treatment in transplant and non-transplant candidates have markedly improved the anti-myeloma efficacy of the different therapeutic regimens and improved patients’ prognosis. Current treatment objectives are focused to further improve the rate of complete remission, time to progression, progression-free survival and overall survival without increasing toxicity. Besides, different strategies are being developed in the elderly population as this group of patients requires a closer monitoring with individualized, dose-modified regimens to improve tolerability while maintaining their…
Flt3 ligand lessens the growth of tumors obtained after colon cancer cell injection in rats but does not restore tumor-suppressed dendritic cell func…
2000
A defective function of the antigen-presenting cells may represent one of the ways used by cancer cells to escape the immune response. We have previously shown that human and rat colon carcinomas were infiltrated by dendritic cells that did not express the B7 co-stimulatory molecules required for inducing an efficient T-cell response. Flt3 ligand is a cloned hematopoietic growth factor that markedly augments the number of functional dendritic and NK cells in lymphoid and non-lymphoid tissues and exerts anti-tumor activity in various experimental models. We show here that repeated Flt3 ligand administration delays the s.c. growth of rat colon cancer cells in syngeneic animals without inducin…
A bioactive designer cytokine for human hematopoietic progenitor cell expansion
1997
Efficient expansion of hematopoietic progenitor cells requires, at least, the simultaneous stimulation of the receptors c-kit and gp130. While c-kit is activated by SCF; gp130, in cells which do not express sufficient amounts of IL-6R, can be activated by the complex of soluble IL-6R (sIL-6R) and IL-6. The therapeutic use of IL-6/sIL-6R, however, has been hampered by the high concentrations of the sIL-6R protein required. We have designed a fusion protein of sIL-6R and IL-6, linked by a flexible peptide chain, that was expressed to high levels. On gp130 expressing cells the fusion protein turned out to be fully active at 100 to 1,000-fold lower concentration than the combination of unlinked…
Polyketides from the marine-derived fungus Aspergillus falconensis: In silico and in vitro cytotoxicity studies.
2020
Abstract Fermentation of the marine-derived fungus Aspergillus falconensis, isolated from sediment collected from the Red Sea, Egypt on solid rice medium containing 3.5% NaCl yielded a new dibenzoxepin derivative (1) and a new natural isocoumarin (2) along with six known compounds (3–8). Changes in the metabolic profile of the fungus were induced by replacing NaCl with 3.5% (NH4)2SO4 that resulted in the accumulation of three further known compounds (9–11), which were not detected when the fungus was cultivated in the presence of NaCl. The structures of the new compounds were elucidated by HRESIMS and 1D/2D NMR as well as by comparison with the literature. Molecular docking was conducted fo…
Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow
2014
How stem cells interact with the microenvironment to regulate their cell fates and metabolism is largely unknown. Here we demonstrated that the deletion of the cytoskeleton-modulating protein profilin 1 (pfn1) in hematopoietic stem cell (HSCs) led to bone marrow failure, loss of quiescence, and mobilization and apoptosis of HSCs in vivo. A switch from glycolysis to mitochondrial respiration with increased reactive oxygen species (ROS) level was also observed in HSCs on pfn1 deletion. Importantly, treatment of pfn1-deficient mice with the antioxidant N-acetyl-l-cysteine reversed the ROS level and loss of quiescence of HSCs, suggesting that the metabolism is mechanistically linked to the cell…
Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D
2017
A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.
The role of signal transducers and activators of transcription in T inflammatory bowel diseases.
2003
Signal transducers and activators of transcription (STAT) proteins are intracellular effector molecules of cytokine-modulated signaling. On the one hand, they play an important role in hematopoiesis and the development of the human immune system. STAT transcription factors are necessary for embryogenesis and the maintenance of the mammalian immune response. In the adult, STAT signaling is responsible for T-cell polarization toward interferon gamma-secreting Th1 T cells or interleukin 4-producing Th2 cells. On the other hand, these proteins are involved in the regulation of T-cell survival. STAT activation is strongly associated with tyrosine phosphorylation by tyrosine kinases, namely Jak1,…
Targeting multiple myeloma with natural polyphenols
2019
Multiple myeloma (MM) is still an incurable hematologic malignancy. Although new therapeutic strategies have been developed to target different pathways in malignant cells, such as proliferation, differentiation, and apoptosis, better survival rates have also been achieved by the introduction of autologous stem cell transplantation (ASCT). Hematopoietic stem cell transplantation and novel targeted agents, such as proteasome inhibitors, monoclonal antibodies, immunomodulatory drugs, check-point inhibitors and epigenetic modulators, have significantly achieved long remission time and increased survival rates. However, most patients relapse, develop resistance, and eventually die because of re…
Hospital and outpatient models for Hematopoietic Stem Cell Transplantation: A systematic review of comparative studies for health outcomes, experienc…
2021
The number of Hematopoietic Stem Cell Transplantations has risen in the past 20 years. The practice of outpatient Hematopoietic Stem Cell Transplantation programs is increasing in an attempt to improve the quality of patient care and reduce the demand for hospital admission. A systematic review of 29 comparative studies between in-hospital and outpatient treatment of Hematopoietic Stem Cell Transplantation, with no restriction by outpatient regime was conducted. This study aims to analyse the current evidence on the effects of the outpatient model on patient-centred outcomes, comparing both in-hospital and outpatient models for autologous and allogeneic HSCT using the Triple Aim framework: …
Bio-inorganic Nanomaterials for Biomedical Applications (Bio-silica and Polyphosphate)
2014
Bio-silica represents the main mineral component of the sponge skeletal elements (siliceous spicules), while bio-polyphosphate (polyP), a multifunctional polymer existing in microorganisms and animals, acts, among others, as reinforcement for pores in cell membranes. These natural inorganic bio-polymers, which can be readily prepared, either by recombinant enzymes (bio-silica and polyP) or chemically (polyP), are promising materials/substances for the amelioration and/or treatment of human bone diseases and dysfunctions. Bone defects in human, caused by fractures/nonunions or trauma, have an increasing impact and have become a medical challenge in the present-day aging population. Frequentl…