Search results for "Multiple"
showing 10 items of 2678 documents
Expression of the IAPs in multidrug resistant tumor cells
2003
We have investigated the expression of the IAPs (inhibitory of apoptosis proteins) in the human HL-60 leukemia and in its multidrug resistant, P-glycoprotein (P-gp) over-expressing variant, HL-60R. HL-60R exhibits resistance to apoptosis induced from P-gp substrate drugs and also from other triggers (cisplatin, TNF-alpha, Fas ligation, TRAIL, IFN-gamma and serum starvation) not related to the multidrug transporter. Except for c-IAP-1 mRNA, HL-60R significantly over-expressed both the mRNAs and the proteins of all the IAPs studied, i.e. c-IAP-1, c-IAP-2, XIAP, NAIP and survivin. Determination of the DNA-binding capacity of NF-kappaB (p50 or p65 subunits) indicated that, while HL-60 cells sho…
Bortezomib: a new pro-apoptotic agent in cancer treatment.
2010
Bortezomib is a proteasome inhibitor. It targets the ubiquitin-proteasome pathway with subsequent inhibition of the degradation of proteins involved in cell cycle regulation and cancer cell survival. The best known molecular mechanism concerns the inhibition of IkappaB breakdown and the related stabilization of NFkappaB, thus preventing its translocation to the nucleus for the activation of downstream pathways. Bortezomib is the only drug in this class which has been approved for clinical use. It has shown an efficient antitumor effect in a phase III clinical trial (APEX) involving relapsed multiple myeloma patients. Response rate, time to progression and overall survival have been improved…
Whole-epigenome analysis in multiple myeloma reveals DNA hypermethylation of B cell-specific enhancers
2015
Abstract Analyzing the DNA methylome of multiple myeloma (MM), a plasma cell neoplasm, by whole-genome bisulfite sequencing and high-density arrays, we observed regional DNA hypermethylation embedded in extensive global hypomethylation. In contrast to the widely reported DNA hypermethylation of promoter-associated CpG islands (CGIs) in cancer, hypermethylated sites in MM as compared to normal plasma cells were located outside CpG islands and were unexpectedly associated with intronic enhancer regions active in normal B cells. Both RNA-seq and in vitro reporter assays indicated that enhancer hypermethylation is globally associated with downregulation of its host genes. ChIP-seq and DNAseI-se…
Expression of DNA repair proteins hMSH2, hMSH6, hMLH1,O6-methylguanine-DNA methyltransferase and N-methylpurine-DNA glycosylase in melanoma cells wit…
1999
Malignant melanoma is well known for its primary unresponsiveness to chemotherapy. The mechanisms conferring this intrinsic resistance are unclear. In this study, we investigated the role of genes involved in DNA repair in a panel of human melanoma cell variants exhibiting low and high levels of resistance to 4 commonly used drugs in melanoma treatment, i.e., vindesine, etoposide, fotemustine and cisplatin. We show that in melanoma cells exhibiting resistance to cisplatin, etoposide and vindesine, the nuclear content of each of the DNA mismatch repair (MMR) proteins hMLH1, hMSH2 and hMSH6 was reduced by 30–70%. A decreased expression level of up to 80% of mRNAs encoding hMLH1 and hMSH2 was …
Type I keratin cDNAs from the rainbow trout: independent radiation of keratins in fish
2002
Five different type I keratins from a teleost fish, the rainbow trout Oncorhynchus mykiss, have been sequenced by cDNA cloning and identified at the protein level by peptide mass mapping using MALDI-MS. This showed that the entire range of type I keratins detected biochemically in this fish has now been sequenced. Three of the keratins are expressed in the epidermis (subtype Ie), whereas the other two occur in simple epithelia and mesenchymal cells (subtype Is). Among the Is keratins is an ortholog of human K18; the second Is polypeptide is clearly distinct from K18. We raised a new monoclonal antibody (F1F2, subclass IgG1) that specifically recognizes trout Is keratins, with negative react…
From a Better Understanding of the Mechanisms of Action of Histone Deacetylases Inhibitors to the Progress of the Treatment of Malignant Lymphomas an…
2017
Background Notable progress has been made in chemo- and immunotherapy of B-cell lymphomas, but less in the treatment of T-cell lymphomas. Objective Histone deacetylases inhibitors are a potentially useful therapeutic mean, as an epigenetic dysregulation is present in lymphomas, and especially in T-cell types. We aimed to study the progress made in this area. Method A mini-review was achieved using the articles published in PubMed in the last two years and the new patents made in this field. Results Histone deacetylases inhibitors are involved in the derepression of tumor suppressor genes through a histone deacetylase-mediated transcriptional process. Their inhibition is followed by cell cyc…
Apoptotic effects of thiazolobenzimidazole derivatives on sensitive and multidrug resistant leukaemic cells
2001
We investigated the cytotoxic activity of eight thiazolobenzimidazole derivatives on sensitive HL60 and multidrug-resistant (MDR) (HL60R) leukaemia cell lines. The antitumour effects of these compounds were compared with those of RS-TBZ, a thiazolobenzimidazole derivative, previously described in our reports, that was able to induce apoptosis more markedly in MDR cells than in the parental sensitive cell lines. Only two compounds in this study proved to have interesting effects: (a) the S-enantiomer of TBZ, that was able to induce apoptosis in MDR cells in a slightly more selective manner than TBZ (racemic form); and (b) TBZ-4-OCH3 (TBZ-4-OCH3), that showed cytotoxic and apoptotic effects o…
Uncommon Synchronous Association between Ovarian Carcinoma and Gastrointestinal Stromal Tumor: A Case Study and Literature Review
2013
Background The association of gastrointestinal stromal tumors (GIST) and other cancers is well known, but its synchronous occurrence with gynecological malignancies is very uncommon. Usually, the diagnosis is accidentally established. We describe a patient with GIST and concurrent ovarian cancer and discuss the clinical implications of this finding. Case report A 64-year-old woman with a prior diagnosis of ovarian cancer developed a second recurrence after having undergone two operations and adjuvant chemotherapy. While tumor debulking was performed, a small, nonsuspicious lesion was removed from the greater curvature of the stomach. Histology revealed a GIST. Conclusion The association of …
Altered Expression of c-IAP1, Survivin, and Smac Contributes to Chemotherapy Resistance in Thyroid Cancer Cells
2006
Abstract Resistance to chemotherapy predicts an unfavorable outcome for patients with radioiodine-insensitive thyroid cancer. To investigate the mechanisms underlying this resistance, we evaluated the expression of four different inhibitor of apoptosis proteins, and their antagonist, Smac, in thyroid cancer cells that survived 48 hours of exposure to cisplatin, doxorubicin, or taxol. We found high levels of c-IAP1 after cisplatin treatment and increased expression of survivin following exposure to doxorubicin. Cells that endured treatment with taxol showed reduced expression of Smac and released minimal amounts of this protein from the mitochondria. Down-regulation of c-IAP1 and survivin in…
Abstract 5379: Recurrent inactivation of PARD3, a polarity-related gene, in squamous cell carcinomas of the lung.
2013
Abstract In spite of the recent advances in cancer genomics, the genetics underlying the development of lung squamous cell carcinomas (SCC) is still poorly understood. Here, we investigated the contribution of the cell polarity-related gene, PARD3, to lung SCC carcinogenesis. First, we tested for PARD3 alterations in lung cancer cell lines from various histopathological types. The analysis confirmed an intragenic deletion at the H157 cells and unveiled biallelic mutations in another cell line. Both cell lines are SCCs, which circumscribed PARD3 alterations to this lung cancer type. Next, we extended the genetic screening, which included the determination of mutations and of intragenic delet…