Search results for " apoptosi."

Topotecan triggers apoptosis in p53-deficient cells by forcing degradation of XIAP and survivin thereby activating caspase-3-mediated Bid cleavage.

2009

The topoisomerase I inhibitor topotecan (TPT) is used in the therapy of different tumors including high-grade gliomas. We previously showed that TPT-induced apoptosis depends on p53 with p53 wild-type (wt) cells being more resistant because of p53-controlled degradation of topoisomerase I. Here, we show that p53-deficient (p53(-/-)) fibroblasts undergo excessive mitochondrial apoptosis featuring H2AX phosphorylation, Bcl-x(L) decline, cytochrome c release, caspase-9/-3/-2 activation, and cleavage of Bid. In wt and apaf-1(-/-) cells, caspase-2 did not become activated and Bid was not cleaved. In addition, p53(-/-) cells cotreated with TPT and caspase-3 inhibitor showed neither caspase-2 acti…

Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism.

2014

Background Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder in which leukemic cells display a reciprocal t(9:22) chromosomal translocation that results in the formation of the chimeric BCR-ABL oncoprotein, with a constitutive tyrosine kinase activity. Consequently, BCR-ABL causes increased proliferation, inhibition of apoptosis, and altered adhesion of leukemic blasts to the bone marrow (BM) microenvironment. It has been well documented that cancer cells can generate their own signals in order to sustain their growth and survival, and recent studies have revealed the role of cancer-derived exosomes in activating signal transduction pathways involved in cancer cell…

Carbon monoxide improves cardiac energetics and safeguards the heart during reperfusion after cardiopulmonary bypass in pigs

2004

Ischemia-reperfusion injury, a clinical problem during cardiac surgery, involves worsened adenosine trisphosphate (ATP) generation and damage to the heart. We studied carbon monoxide ( CO) pretreatment, proven valuable in rodents but not previously tested in large animals, for its effects on pig hearts subjected to cardiopulmonary bypass with cardioplegic arrest. Hearts of CO-treated pigs showed significantly higher ATP and phosphocreatine levels, less interstitial edema, and apoptosis of cardiomyocytes and required fewer defibrillations after bypass. We conclude that treatment with CO improves the energy status, prevents edema formation and apoptosis, and facilitates recovery in a clinical…

Regulation of T-cell apoptosis in inflammatory bowel disease: to die or not to die, that is the mucosal question.

2001

T-cell resistance against apoptosis contributes to inappropriate T-cell accumulation and the perpetuation of chronic mucosal inflammation in inflammatory bowel diseases (IBDs). Anti-interleukin-12 (IL-12) and anti-IL-6 receptor antibodies suppress colitis activity by the induction of T-cell apoptosis. These findings have important implications for the design of effective treatment regimens in IBD.

cIAP1-dependent TRAF2 degradation regulates the differentiation of monocytes into macrophages and their response to CD40 ligand.

2008

AbstractPeripheral blood monocytes are plastic cells that migrate to tissues and differentiate into various cell types, including macrophages, dendritic cells, and osteoclasts. We have described the migration of cellular inhibitor of apoptosis protein 1 (cIAP1), a member of the IAP family of proteins, from the nucleus to the Golgi apparatus in monocytes undergoing differentiation into macrophages. Here we show that, once in the cytoplasm, cIAP1 is involved in the degradation of the adaptor protein tumor necrosis factor receptor–associated factor 2 (TRAF2) by the proteosomal machinery. Inhibition of cIAP1 prevents the decrease in TRAF2 expression that characterizes macrophage formation. We d…

Multidrug resistance reverting activity and antitumor profile of new phenothiazine derivatives

2008

Abstract A series of easily affordable phenothiazine derivatives bearing a rigid but-2-ynyl amino side chain were synthesized and tested to evaluate the MDR reverting activity and full antitumor profile. Some compounds endowed with remarkable MDR reverting effect were identified, and the most active one ( 6c ) was shown to increase doxorubicin retention in multidrug resistant cells, suggesting a direct interaction with P-glycoprotein. Furthermore, a broad range of cellular activities were observed for different compounds. In particular, the ability of some derivatives to induce antiproliferative effects on resistant cell lines and to interfere with the G 1 phase of the cell cycle, a phase u…

Studio dell’apoptosi in oociti umani.

2017

Gli obiettivi delle ricerche condotte sono stati duplici: 1) verificare l’eventuale comparsa o aumento di fenomeni apoptotici nelle cellule follicolari, negli oociti e nelle strutture stromali, di tessuto ovarico sottoposto a criopreservazione. 2) verificare la presenza di apoptosi in oociti non fecondati dopo trattamento ICSI (Intra Citoplasmic Sperm Injection), per comprendere se pregressi eventi apoptotici siano già in atto in oociti umani trattati con tecniche avanzate di fecondazione assistita, e possano pertanto essere la causa della mancata fecondazione di circa il 30-35 % degli oociti trattati.

Apoptosis in Thyroid Autoimunity.

2007

Cadmium regulation of apoptotic and stress response genes in tumoral and immortalized epithelial cells of the human breast

2008

Cadmium (Cd) is a widely-disseminated metal which can be imported and accumulated in living cells thereby drastically interfering with their biological mechanisms. Increasing interest has been recently focused on the elucidation of the cellular and molecular aspects of Cd-dependent regulation of gene expression and signal transduction pathways in different model system. Concerning breast cancer, very limited studies have been produced so far on the role played by Cd on estrogen receptor-negative human breast cancer cells, that are expected to be insensitive to the already-proven metallo-estrogenic effect exerted by Cd on the estrogen receptor-positive cell counterparts. Here, we have examin…

Let-7d miRNA Shows Both Antioncogenic and Oncogenic Functions in Osteosarcoma-Derived 3AB-OS Cancer Stem Cells

2015

Osteosarcoma (OS), an aggressive highly invasive and metastatic bone-malignancy, shows therapy resistance and recurrence, two features that likely depend on cancer stem cells (CSCs), which hold both self-renewing and malignant potential. So, effective anticancer therapies against OS should specifically target and destroy CSCs. We previously found that the let-7d microRNA was downregulated in the 3AB-OS-CSCs, derived from the human OS-MG63 cells. Here, we aimed to assess whether let-7d modulation affected tumorigenic and stemness properties of these OS-CSCs. We found that let-7d-overexpression reduced cell proliferation by decreasing CCND2 and E2F2 cell-cycle-activators and increasing p21 an…