Search results for "Cytotoxic"
showing 10 items of 1673 documents
Cytokines with Possible Clinical Utility
1987
Biological response modifiers (BRM) are agents aimed at reducing tumor growth, not primarily by exerting direct cytotoxic effects but by modulation of tumor gene expression (e.g., induction of differentiation) or by enhancing host defense mechanisms directed against cancer cells. BRM as primary therapy or as adjuncts to cytotoxic agents in the treatment of cancers have attracted increasing interest in view of stagnating clinical results in many areas [1], and there is increasing evidence of in vitro and in vivo efficacy of these agents. Furthermore, advances in molecular biology suggesting that oncogenes and their products play a crucial role in oncogenesis support approaches to modulation …
SYNTHESIS AND PHOTOCHEMIOTHERAPEUTIC ACTIVITY OF THIOPYRANO[2,3-E]INDOL-2-ONES
2004
A series of derivatives of the new ring system thiopyrano[2,3-e]indol-2-one was prepared with the aim of obtaining new photochemotherapeutic drugs. Biological screenings were performed on this new class of photoactivable drugs and a strong antiproliferative effect was observed upon irradiation with UVA light. The compound bearing a methyl substituent at the pyrrole nitrogen resulted as the most interesting showing IC50 in the nanomolar range.
Synthesis and evaluation of microtubule assembly inhibition and cytotoxicity of prenylated derivatives of cyclo-l-Trp-l-Pro
2000
The synthesis of three isoprenylated derivatives of cyclo-L-Trp-L-Pro is described. These substances have been evaluated for cytotoxic activity in rat normal fibroblast 3Y1 cells and have also been evaluated in vitro for the inhibition of microtubule assembly.
Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review
2019
Background Vaccine adjuvants are compounds that significantly enhance/prolong the immune response to a co-administered antigen. The limitations of the use of aluminium salts that are unable to elicite cell responses against intracellular pathogens such as those causing malaria, tuberculosis, or AIDS, have driven the development of new alternative adjuvants such as QS-21, a triterpene saponin purified from Quillaja saponaria. Purpose The aim of this review is to attempt to clarify the mechanism of action of QS-21 through either receptors or signaling pathways in vitro and in vivo with special emphasis on the co-administration with other immunostimulants in new adjuvant formulations, called a…
Cigarette smoke promotes inflammasome‐independent activation of caspase‐1 and ‐4 leading to gasdermin D cleavage in human macrophages
2022
Mechanisms and consequences of gasdermin D (GSDMD) activation in cigarette smoke (CS)-associated inflammation and lung disease are unknown. GSDMD is a downstream effector of caspase-1, -8, and -4. Upon cleavage, GSDMD generates pores into cell membranes. Different degrees of GSDMD activation are associated with a range of physiological outputs ranging from cell hyperactivation to pyroptosis. We have previously reported that in human monocyte-derived macrophages CS extract (CSE) inhibits the NLRP3 inflammasome and shifts the response to lipopolysaccharide (LPS) towards the TLR4-TRIF axis leading to activation of caspase-8, which, in turn, activates caspase-1. In the present work, we investig…
Drug-induced expansion and differentiation of Vγ9Vδ2 T cells in vivo: The role of exogenous IL-2
2005
Human Vgamma9Vdelta2 T cells recognize nonpeptidic Ags generated by the 1-deoxy-d-xylulose 5-phosphate (many eubacteria, algae, plants, and Apicomplexa) and mevalonate (eukaryotes, archaebacteria, and certain eubacteria) pathways of isoprenoid synthesis. The potent Vgamma9Vdelta2 T cell reactivity 1) against certain cancer cells or 2) induced by infectious agents indicates that therapeutic augmentations of Vgamma9Vdelta2 T cell activities may be clinically beneficial. The functional characteristics of Vgamma9Vdelta2 T cells from Macaca fascicularis (cynomolgus monkey) are very similar to those from Homo sapiens. We have found that the i.v. administration of nitrogen-containing bisphosphonat…
Transcription Factors Controlling Innate Lymphoid Cell Fate Decisions
2014
The mucosal epithelium is in direct contact with symbiotic and pathogenic microorganisms. Therefore, the mucosal surface is the principal portal of entry for invading pathogens and immune cells accumulated in the intestine to prevent infections. In addition to these conventional immune system functions, it has become clear that immune cells during steady-state continuously integrate microbial and nutrient-derived signals from the environment to support organ homeostasis. A major role in both processes is played by a recently discovered group of lymphocytes referred to as innate lymphoid cells (ILCs) that are specifically enriched at mucosal surfaces but are rather rare in secondary lymphoid…
A New 1D Ni (II) Coordination Polymer of s-Triazine Type Ligand and Thiocyanate as Linker via Unexpected Hydrolysis of 2,4-Bis(3,5-dimethyl-1H-pyrazo…
2023
A new 1D Ni(II) coordination polymer was synthesized by the reaction of NiSO4·6H2O with 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine (BPT) and SCN− as a linker in an acidic medium by heating under reflux conditions. Unusually, the BPT ligand underwent acid-mediated hydrolysis by losing one of the pyrazolyl arms afforded the polymeric [Ni(MPT)(H2O)(SCN)2]n complex (MPT: 4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazin-2-ol. The Ni(II) center is coordinated with one MPT as a bidentate NN-chelate, one water molecule, and two thiocyanate groups in cis positions to one another. One of the thiocyanate groups acts as a bridging ligand between metal centers, l…
Preclinical immunomodulation by the probiotic Bifidobacterium breve M-16V in early life
2016
This study aimed to investigate the effect of supplementation with the probiotic Bifidobacterium breve M-16V on the maturation of the intestinal and circulating immune system during suckling. In order to achieve this purpose, neonatal Lewis rats were supplemented with the probiotic strain from the 6th to the 18th day of life. The animals were weighed during the study, and faecal samples were obtained and evaluated daily. On day 19, rats were euthanized and intestinal wash samples, mesenteric lymph node (MLN) cells, splenocytes and intraepithelial lymphocytes (IEL) were obtained. The probiotic supplementation in early life did not modify the growth curve and did not enhance the systemic immu…
Human CD25+ regulatory T cells: two subsets defined by the integrins alpha 4 beta 7 or alpha 4 beta 1 confer distinct suppressive properties upon CD4…
2004
Down-regulation of autoreactive T cell responses in vivo includes cell-contact-dependent as well as contact-independent mechanisms. Infectious tolerance is a contact-dependent mechanism used by naturally occurring CD25(+) T regulatory cells (Tregs) to confer suppressive activity upon conventional CD4(+) T cells thereby generating secondary T helper suppressor cells(Th(sup)), which inhibit T cell activation via soluble mediators. Here, we describe two distinct subsets of human Tregs, characterized by expression of either the alpha(4)beta(7) integrin or the alpha(4)beta(1) integrin. Upon activation, both subsets show an enhanced expression of FoxP3, recently described as a key transcription f…