Search results for "Apoptosi"
showing 10 items of 1846 documents
Antiphosphatidylserine Antibodies Affect Rat Yolk Sacs in Culture: a Mechanism for Fetal Loss in Antiphospholipid Syndrome
2004
PROBLEM: A variety of reproductive impairments have been reported in the context of the antiphospholipid syndrome (APS). APS is associated with the presence of antibodies to negatively charged phospholipids that may affect the outcome of pregnancy. METHOD OF STUDY: Rat embryos were cultured within their yolk sacs. The effects of two antiphosphatidylserine monoclonal aPS antibodies (HL5B, RR7F) regarding their influence on growth and apoptotic events of the yolk sacs, as well as on growth and the morphology of the embryos, were studied. RESULTS: Exposure of rat embryos and their yolk sacs to aPS inhibited yolk sac growth. Moreover, increased number of apoptotic events of giant cells in the a…
Bafetinib inhibits functional responses of human eosinophils in vitro
2012
Eosinophils play a prominent role in the process of allergic inflammation. Non-receptor associated Lyn tyrosine kinases generate key initial signals in eosinophils. Bafetinib, a specific Abl/Lyn tyrosine kinase inhibitor has shown a potent antiproliferative activity in leukemic cells, but its effects on eosinophils have not been reported. Therefore, we studied the effects of bafetinib on functional and mechanistic responses of isolated human eosinophils. Bafetinib was more potent than non-specific tyrosin kinase comparators genistein and tyrphostin inhibiting superoxide anion triggered by N-formyl-Met-Leu-Phe (fMLF; 100 nM) (−log IC50=7.25±0.04 M; 6.1±0.04 M; and 6.55±0.03 M, respectively).…
Possible Pathogenetic Relevance of Interleukin-1beta in "Destructive" Organ-specific Autoimmune Disease (Hashimoto's Thyroiditis)
1999
Thyroid follicular cells (TFC) abundantly express a variety of immunologically relevant surface molecules in Hashimoto's thyroiditis (HT), for example, MHC antigens and adhesion molecules such as ICAM-1. Cytokines produced by infiltrating type 1 helper and cytotoxic T cells are importantly involved in de novo expression or up-regulation of such molecules. We recently demonstrated that TFC from HT patients almost invariably bear on their surface two additive functional molecules: Fas/Apo1/CD95, an important participant in apoptosis, and B7.1, a member of a family of "co-stimulatory" molecules that are crucial for efficient antigen presentation. To date, 12 out of 14 surgical HT thyroid speci…
Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells
2013
Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex®) is a selective cyclooxygenase-2 (COX-2) inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth an…
Bortezomib Induces Anti–Multiple Myeloma Immune Response Mediated by cGAS/STING Pathway Activation
2021
Abstract The proteasome inhibitor bortezomib induces apoptosis in multiple myeloma cells and has transformed patient outcome. Using in vitro as well as in vivo immunodeficient and immunocompetent murine multiple myeloma models, we here show that bortezomib also triggers immunogenic cell death (ICD), characterized by exposure of calreticulin on dying multiple myeloma cells, phagocytosis of tumor cells by dendritic cells, and induction of multiple myeloma–specific immunity. We identify a bortezomib-triggered specific ICD gene signature associated with better outcome in two independent cohorts of patients with multiple myeloma. Importantly, bortezomib stimulates multiple myeloma cell immunogen…
Synthetic multivalent glycopeptide-lipopeptide antitumor vaccines: impact of the cluster effect on the killing of tumor cells.
2014
Multivalent synthetic vaccines were obtained by solid-phase synthesis of tumor-associated MUC1 glycopeptide antigens and their coupling to a Pam3 Cys lipopeptide through click reactions. These vaccines elicited immune responses in mice without the use of any external adjuvant. The vaccine containing four copies of a MUC1 sialyl-TN antigen showed a significant cluster effect. It induced in mice prevailing IgG2a antibodies, which bind to MCF-7 breast tumor cells and initiate the killing of these tumor cells by activation of the complement-dependent cytotoxicity complex.
DNA fragmentation index, pAKT and pERK1/2 in cumulus cells are related to oocyte competence in patients undergoing in vitro fertilization programme
2019
SummaryActivated pERK1/2 and pAKT are key players in supporting cell survival and proliferation pathways. Translocation of pERK1/2 into the nucleus, where it interacts with transcription factors and DNA itself, is instrumental in exerting an anti-apoptotic effect. In this study, pAKT levels, pERK1/2 nuclear localization and DNA fragmentation index (DFI) in cumulus cells of single cumulus–oocyte complexes of patients undergoing in vitro fertilization programmes were evaluated and correlated with the clinical outcome of the related embryos. For a positive clinical outcome of blastocyst development, pERK1/2 nuclear localization and DFI value had a significant inverse relationship, whereas the …
Dexrazoxane shows cytoprotective effects in zoledronic acid-treated human cells in vitro and in the rabbit tibia model in vivo
2012
Abstract Introduction Bisphosphonates are important and effective drugs in oncology and osteoporosis therapy. They accumulate in the bone matrix becoming released and active by bone resorption. This leads to effective inhibition of tumor cells and bone degradation. A side effect of bisphosphonates similar to other drugs like denosumab is osteonecrosis of the jaws (ONJ). This problem mostly occurs after tooth extraction. We studied the cytoprotectant dexrazoxane known from anthracycline chemotherapy for cytoprotection in nitrogen-containing bisphosphonate treated cells and in the rabbit tibia model to evaluate a possible value in ONJ management. Materials & methods Human osteoblasts (HOB) P2…
Papel de la mitocondria en la neurodegeneración de las neuropatías periféricas
2014
La disfunción mitocondrial tiene severas consecuencias a nivel celular, y está íntimamente relacionada con el proceso de envejecimiento. Pero además, la mitocondria juega un importante papel en la muerte celular progresiva característica de algunos trastornos neurodegenerativos, de forma que la disfunción mitocondrial ha surgido como un denominador común en varias enfermedades neurodegenerativas. En la presente Tesis Doctoral nos hemos centrado en el estudio de los mecanismos patogénicos que conducen a la degeneración neuronal de dos neuropatías periféricas diferentes, pero relacionadas: ataxia de Friedreich (FRDA) y la enfermedad de Charcot-Marie-Tooth (CMT) tipos 4A/2K. Ambas enfermedades…
ShRNA-mediated knock-down of CXCL8 inhibits tumor growth in colorectal liver metastasis.
2018
CXCL8 belongs to proinflammatory chemokines that are predominantly involved in neutrophil chemotaxis and degranulation. Several studies have suggested that secretion of CXCL8 from cancer cells have a profound effect on tumor microenvironment. In this study, in continuation to our previous work of understanding the global picture of invasion related genes in colorectal liver metastases, we clearly show an up-regulation of CXCL8 expression in the tumor cells at the invasion front as compared to the tumor cells in the inner parts of the tumor. Furthermore, ShRNA mediated down-regulation of CXCL8 resulted in inhibition of cell proliferation, viability and invasion in vitro and a near complete g…