Search results for "antineoplastic"
showing 10 items of 2217 documents
Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis
2011
Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified a mutant of HSP110 (HSP110ΔE9) in colorectal cancer showing microsatellite instability (MSI CRC), generated from an aberrantly spliced mRNA and lacking the HSP110 substrate-binding domain. This mutant was expressed at variable levels in almost all MSI CRC cell lines and primary tumors tested. HSP110ΔE9 impaired both the normal cellular localization of HSP110 and its interaction with other HSPs, thus abrogating the chaperone activity and antiapoptotic function of HSP110 in a dominant-negative manner. HSP110ΔE9 overexpression caused the sensitization of cells to anticancer agents such as oxaliplatin and 5-fluorou…
Survivin is regulated by interleukin-4 in colon cancer stem cells
2010
Colorectal cancer has provided an important model to test the stem cell hypothesis of cancer origin, which implies that cancer arises as a result of genetic aberrations in stem cells leading to deregulation of the proliferation/differentiation balance. We and others have demonstrated that, similarly to other solid tumors, colon carcinogenesis and progression are dictated by highly apoptosis-resistant stem-like cells. Our data have suggested that protection from apoptosis is achieved by autocrine production of interleukin-4 (IL-4) through up-regulation of anti-apoptotic mediators. In this study, we extend our analysis to another apoptosis inhibitor widely expressed in tumors, namely survivin…
New heteronuclear gold(I)-platinum(II) complexes with cytotoxic properties: are two metals better than one?
2014
A series of mono- and heterodinuclear gold(I) and platinum(II) complexes with a new bipyridylamine-phosphine ligand have been synthesized and characterized. The X-ray structures of the ligand precursor 4-iodo-N,N-di(pyridin-2-yl)benzamide, and of one gold derivative are reported. All the complexes display antiproliferative properties in vitro in human cancer cells in the range of cisplatin or higher, which appear to correlate with compounds' uptake. Interestingly, studies of the interactions of the compounds with models of DNA indicate different mechanisms of actions with respect to cisplatin. The biological activity study of these complexes provides useful information about the interest of…
cis-Dichloroplatinum(II) complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-ones: Synthesis and cytotoxicity in human cancer cell lines in vitro
2013
A novel family of cisplatin-type complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-one topoisomerase inhibitor via a polymethylene chain and their nonplatinated counterparts were prepared. Their potential cytotoxicity was assessed in three human colorectal cancer cell lines HCT 116, SW480 and HT-29 and compared to the reference molecules cisplatin and oxaliplatin. Platinated compounds were poorly active whilst nonplatinated dibenzo[c,h][1,6]naphthyridin-6-one moieties exhibited higher cytotoxic properties than cisplatin and oxaliplatin whatever the length of the polymethylene chain; molecules containing the tri- and hexamethylene chain length were the most cytotoxic.
Membrane gangliosides and immuno-mediated cytolysis in drug sensitive and treatment-induced multidrug resistant human ovarian cancer cells
1991
The pattern of cytoplasmic membrane gangliosides and two cellular features which have been reported to be related to the expression of different membrane gangliosides, namely adhesion to solid substrates and susceptibility to the lytic activity of immune effector cells, have been investigated in drug sensitive A2780 human ovarian cancer cells and in two treatment-induced multidrug resistant sublines (A2780-DX1 and A2780-DX3). The total membrane gangliosides content of A2780 sensitive cells was comparable to that of the two multidrug resistant (MDR) sublines, but the acquisition of the MDR phenotype was characterized by an increased expression of the polysialylated gangliosides (particularly…
Metal complexes of oxadiazole ligands: An overview
2019
Oxadizoles are heterocyclic ring systems that find application in different scientific disciplines, from medicinal chemistry to optoelectronics. Coordination with metals (especially the transition ones) proved to enhance the intrinsic characteristics of these organic ligands and many metal complexes of oxadiazoles showed attractive characteristics for different research fields. In this review, we provide a general overview on different metal complexes and polymers containing oxadiazole moieties, reporting the principal synthetic approaches adopted for their preparation and showing the variety of applications they found in the last 40 years.
French Endocrine Society Guidance on endocrine side effects of immunotherapy.
2018
The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPIs). However, the use of ICPI has a risk of side effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, and we will then outline expert opinion focusing…
Between Scylla and Charibdis: eIF2α kinases as targets for cancer chemotherapy
2011
[EN] The eIF2 alpha kinases integrate translation initiation rates with nutrient availability, thus allowing cells to adapt to nutrient scarcity. Recent evidence has uncovered new functions of these kinases in tumour cell biology, ranging from regulation of cell cycle progression, maintenance of genome stability, control of apoptosis, and cell survival under nutrient stress and hypoxia. Accordingly, active eIF2 alpha kinases modulate the antineoplasic activity of several antitumour drugs, either by exacerbating their cytotoxic effect or by promoting chemoresistance. Understanding of eIF2 alpha kinases molecular roles may provide mechanistic insights into how tumour cells sense and adapt to …
The dark side of the moon: The PI3K/PTEN/AKT pathway in colorectal carcinoma
2009
Wild-type KRAS status is required but not sufficient to confer sensitivity to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) in colorectal cancer patients. As a consequence, one of the major challenges is to identify, in non-mutant KRAS patients, other markers that can predict lack of response to this therapy. Small series have investigated the clinical effect of PIK3CA mutations on resistance to anti-EGFR mAbs and discrepant results have been observed. Furthermore, PTEN loss in metastases may be predictive of resistance to anti-EGFR mAbs, even if PTEN determination is far from an immediate clinical application. The introduction of modulators of the PI3K/AKT/mTOR …
Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy
2012
An area of therapeutic interest in cancer biology and treatment is targeting the cancer stem cell, more appropriately referred to as the cancer initiating cell (CIC). CICs comprise a subset of hierarchically organized, rare cancer cells with the ability to initiate cancer in xenografts in genetically modified murine models. CICs are thought to be responsible for tumor onset, self-renewal/maintenance, mutation accumulation and metastasis. CICs may lay dormant after various cancer therapies which eliminate the more rapidly proliferating bulk cancer (BC) mass. However, CICs may remerge after therapy is discontinued as they may represent cells which were either intrinsically resistant to the or…