Search results for "Neoplastic"
showing 10 items of 2901 documents
The role of hypoxia-induced factors in tumor progression.
2004
Abstract Learning Objectives After completing this course, the reader will be able to: Describe hypoxia-induced mechanisms for cell survival. Discuss hypoxia-induced gene expression. Relate hypoxia and glucose metabolism. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit atCME.TheOncologist.com Hypoxia is a common characteristic of locally advanced solid tumors that has been associated with diminished therapeutic response and, more recently, with malignant progression, that is, an increasing probability of recurrence, locoregional spread, and distant metastasis. Emerging evidence indicates that the effect of hypoxia on malignant progression is mediated by a…
Comparative activity of idarubicin and idarubicinol in combination with cyclosporin A in multidrug-resistant leukemia cells
1996
4-Demethoxydaunorubicin (idarubicin, IDA) is an anthracycline that has shown good cytotoxic activity in vitro against tumor cell lines displaying the multidrug-resistant (MDR) phenotype. IDA is converted in the liver into idarubicinol (2HIDA) and, in this form, seems to exert its antitumoral activity in vivo. Recent studies have shown that 2HIDA has tumoricidal activity similar to that of the parent drug when tested in vitro in sensitive neoplastic cells. In this work we compared in vitro the effects of IDA and 2HIDA used alone and in combination with 2 microM cyclosporin A (CyA) in the MDR leukemic cell lines FLCR and K562R and in their sensitive parent cell lines FLC and K562. IDA and 2HI…
CtIP silencing as a novel mechanism of tamoxifen resistance in breast cancer.
2007
AbstractAcquired resistance to the antiestrogen tamoxifen constitutes a major clinical challenge in breast cancer therapy. However, the mechanisms involved are still poorly understood. Using serial analysis of gene expression, we identified CtIP, a BRCA1- and CtBP-interacting protein, as one of the most significantly down-regulated transcripts in estrogen receptor α–positive (ER+) MCF-7 tamoxifen-resistant breast cancer cells. We further confirmed the association of CtIP down-regulation with tamoxifen resistance in an additional ER+ breast cancer line (T47D), strengthening the relevance of the phenomenon observed. In additional studies, we found CtIP protein expression in a majority of ER+ …
Patterns of Innate or Acquired Resistance to Anticancer Drugs: Our Experience to Overcome It
2021
Drug resistance, which is often of a multiple type, can be defined as the ability of cancer cells to obtain resistance to both conventional and novel chemotherapy agents. It remains a major problem to solve in cancer therapy. The mechanisms of resistance are multifactorial, and in our cellular models of acute myeloid leukemia, hepatocellular carcinoma, and triple-negative breast cancer, it involves the NF-κB pathway. In our opinion, multitarget molecules can be considered as privileged compounds capable of attacking and reversing the resistant phenotype. In the phenomena of both innate and acquired drug resistance that we have been studying since 1998 to today and up to 2016 under the guida…
Inhibition of HSP70: a challenging anti-cancer strategy.
2012
HSP70 is a chaperone that accumulates in the cells after many different stresses promoting cell survival in response to the adverse conditions. In contrast to normal cells, most cancer cells abundantly express HSP70 at the basal level to resist to various insults at different stages of tumorigenesis and during anti-cancer treatment. This cancer cells addiction for HSP70 is the rational for its targeting in cancer therapy. Much effort has been dedicated in the last years for the active search of HSP70 inhibitors. Additionally, the recent clinical trials on highly promising inhibitors of another stress protein, HSP90, showed compensatory increase in HSP70 levels and raised the question of nec…
Natural polyphenols facilitate elimination of HT-29 colorectal cancer xenografts by chemoradiotherapy: a Bcl-2- and superoxide dismutase 2-dependent …
2008
AbstractColorectal cancer is one of the most common malignancies worldwide. The treatment of advanced colorectal cancer with chemotherapy and radiation has two major problems: development of tumor resistance to therapy and nonspecific toxicity towards normal tissues. Different plant-derived polyphenols show anticancer properties and are pharmacologically safe. In vitro growth of human HT-29 colorectal cancer cells is inhibited (∼56%) by bioavailable concentrations of trans-pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene; t-PTER) and quercetin (3,3′,4′,5,6-pentahydroxyflavone; QUER), two structurally related and naturally occurring small polyphenols. I.v. administration of t-PTER and Q…
MYCN sensitizes human neuroblastoma to apoptosis by HIPK2 activation through a DNA damage response.
2010
Abstract MYCN amplification occurs in approximately 20% of human neuroblastomas and is associated with early tumor progression and poor outcome, despite intensive multimodal treatment. However, MYCN overexpression also sensitizes neuroblastoma cells to apoptosis. Thus, uncovering the molecular mechanisms linking MYCN to apoptosis might contribute to designing more efficient therapies for MYCN-amplified tumors. Here we show that MYCN-dependent sensitization to apoptosis requires activation of p53 and its phosphorylation at serine 46. The p53S46 kinase HIPK2 accumulates on MYCN expression, and its depletion by RNA interference impairs p53S46 phosphorylation and apoptosis. Remarkably, MYCN ind…
Malignant transformation of the liver tumour precursor cell line OC/CDE 22 by the four stereoisomeric fjord region 3,4-dihydrodiol 1,2-epoxides of be…
1995
In previous work we established the rat liver oval cell line OC/CDE 22 in order to study in vitro mechanisms of liver cell transformation. We have now exposed OC/CDE 22 cells to each of the four optically active fjord region dihydrodiol epoxides of benzo[c]phenanthrene to investigate their capacity for malignant transformation of liver cells. All four configurational isomers, which are among the most potent carcinogenic metabolites of polycyclic aromatic hydrocarbons tested in murine tumour models, malignantly transform OC/CDE 22 cells at a 2 microM dose level, resulting in a similar colony-forming efficiency in soft agar. Inoculation of the transformed cells into newborn syngeneic rats pro…
Immunomodulation and Anti-inflammatory Roles of Polyphenols as Anticancer Agents
2011
Cancers are the largest cause of mortality and morbidity in industrialized countries. Several new concepts have emerged in relation to mechanisms that contribute to the regulation of carcinogenesis processes and associated inflammatory effects such as the modulation of innate immune cells and adaptive immune cells that could infiltrate the tumor. In the tumor microenvironment, there is a delicate balance between antitumor immunity and tumor-originated proinflammatory activity, which weaken antitumor immunity. Consequently; modulation of immune cells and inflammatory processes represent attractive targets for therapeutic intervention in malignant diseases with the goal to restore the sensiti…
Morphological transformation and DNA adduct formation by dibenz[a,h]anthracene and its metabolites in C3H10T1/2CL8 cells.
1994
The major routes of metabolic activation of dibenz[a,h]-anthracene (DBA) have been studied in transformable C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts in culture. The morphological transforming activities of three potential intermediates formed by metabolism of DBA by C3H10T1/2 cells, trans-3,4-dihydroxy-3,4-dihydro-DBA-(DBA-3,4-diol), trans-dihydroxy-3,4-dihydro-DBA-anti-1,2-oxide (DBA-3,4-diol-1,2-oxide) and DBA-5,6-oxide were determined. DBA-3,4-diol-1,2-oxide was a strong morphological transforming agent giving a mean of 73% dishes with Type II or III foci and 1.63 Type II and III foci per dish at 0.5 microgram/ml. DBA-3,4-diol produced a mean of 42% dishes with Type II or III fo…