DAG&amp;ndash;1 Carcinoma Cell in Studying the  Mechanisms of Progression and Therapeutic  Resistance in Bladder Cancer

Champelovier, Pierre; Besse, Arnaud; Boucard, Nathalie; Simon, Annick; Leroux, D; Pinel, N.; Perreten, Vincent; Seigneurin, Daniel

doi:10.1159/000052465

Cited by 8 publications

(6 citation statements)

References 19 publications

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“…Specifically, reduction of DAG1 may increase susceptibility of muscle fibers to necrosis [ 32 ]. A study shows that DAG-1 cells are resistant to TNF-α and IFNγ -induced apoptosis, with implications in bladder cancer progression and resistance to immunotherapy [ 33 ]. CD27 is part of TNF receptor family, and overexpression of CD27 induces NF-κB activation involving signaling transduction of TNF receptor-associated factors [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

A Predictive 7-Gene Assay and Prognostic Protein Biomarkers for Non-small Cell Lung Cancer

et al. 2018

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PurposeThis study aims to develop a multi-gene assay predictive of the clinical benefits of chemotherapy in non-small cell lung cancer (NSCLC) patients, and substantiate their protein expression as potential therapeutic targets.Patients and methodsThe mRNA expression of 160 genes identified from microarray was analyzed in qRT-PCR assays of independent 337 snap-frozen NSCLC tumors to develop a predictive signature. A clinical trial JBR.10 was included in the validation. Hazard ratio was used to select genes, and decision-trees were used to construct the predictive model. Protein expression was quantified with AQUA in 500 FFPE NSCLC samples.ResultsA 7-gene signature was identified from training cohort (n = 83) with accurate patient stratification (P = 0.0043) and was validated in independent patient cohorts (n = 248, P < 0.0001) in Kaplan-Meier analyses. In the predicted benefit group, there was a significantly better disease-specific survival in patients receiving adjuvant chemotherapy in both training (P = 0.035) and validation (P = 0.0049) sets. In the predicted non-benefit group, there was no survival benefit in patients receiving chemotherapy in either set. The protein expression of ZNF71 quantified with AQUA scores produced robust patient stratification in separate training (P = 0.021) and validation (P = 0.047) NSCLC cohorts. The protein expression of CD27 quantified with ELISA had a strong correlation with its mRNA expression in NSCLC tumors (Spearman coefficient = 0.494, P < 0.0088). Multiple signature genes had concordant DNA copy number variation, mRNA and protein expression in NSCLC progression.ConclusionsThis study presents a predictive multi-gene assay and prognostic protein biomarkers clinically applicable for improving NSCLC treatment, with important implications in lung cancer chemotherapy and immunotherapy.

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Section: Discussionmentioning

confidence: 99%

A Predictive 7-Gene Assay and Prognostic Protein Biomarkers for Non-small Cell Lung Cancer

et al. 2018

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“…Plasminogen activator inhibitor 2 (pAI-2) inhibits the serine proteases urokinase-type and tissue-type plasminogen activator (uPA and tPA, respectively). However, high pAI-2 levels are associated with aggressive disease in colorectal cancer (Verspaget et al, 1995) and in bladder cancer cell lines, pAI-2 expression correlates with tumour stage and with a low overall survival (Champelovier et al, 2002). Paradoxically, in breast cancer, high levels of pAI-2 have been reported to be a favourable prognostic marker (Duggan et al, 1997) and in vitro pAI-2 expression can inhibit cancer cell invasion and metastasis (Mueller et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Maspin – the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer – is strongly expressed in preneoplastic bronchial lesions

et al. 2003

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Maspin, SCCA1/2 and hurpin were identified by cDNA microarray analyses as dramatically differentially expressed transcripts in primary non-small cell lung cancer (NSCLC). These sequences are located within a 10-gene serpin cluster on 18q21.3. Using comparative RT-PCR, we have investigated the expression of each of these serpins, including their flanking loci, in an independent NSCLC series. Whereas six of the genes (maspin, SCCA1, SCCA2, hurpin, megsin and pAI-2) were commonly differentially expressed in primary lesions, each significantly more often in squamous cell tumours, maspin was identified as the most frequently overrepresented sequence in both squamous cell carcinoma and adenocarcinoma. Using a well-characterized monoclonal antibody, we have shown strong maspin expression in tumour protein extracts, detected multiple isoforms of the 42 kDa protein and shown that maspin is localized specifically to the tumour cells within neoplastic lesions. In contrast, most cells in non-neoplastic lung tissue appear not to express the gene, with the exception of the multipotent basal epithelial cells that line the bronchial airway. These reserve cells generally show strong predominantly nuclear localization of maspin. Strong nuclear expression of maspin within primary tumour cells is correlated with increased survival (P ¼ 0.05) and a longer remission duration (P ¼ 0.02) in resectable-staged patients. However, within the airways of cancer patients and somewhat in contrast to this observation, such expression was more frequently detected in the superficial cells of preneoplastic over non-neoplastic epithelia (Po0.0001), consistent with a role for the protein in early neoplasia.

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“…RT112 cells are less invasive than T24 and J82 [50]. Several studies have shown that the viscoelasticity of cancer cells can be a marker of their malignancy [11,45].…”

Section: Mechanical Properties Are a Marker Of Cancer Cell Invasivitymentioning

confidence: 99%

Local mechanical properties of bladder cancer cells measured by AFM as a signature of metastatic potential

et al. 2015

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Abstract. The rheological properties of bladder cancer cells of different invasivities have been investigated using a microrheological technique well adapted in the range [1-300 Hz] of interest to understand local changes in the cytoskeleton microstructure, in particular actin fibres. Drugs disrupting actin and actomyosin functions were used to study the resistance of such cancer cells. Results on a variety of cell lines were fitted with a model revealing the importance of two parameters, the elastic shear plateau modulus G 0 N as well as the glassy transition frequency fT. These parameters are good markers for invasiveness, with the notable exception of the cell periphery, which is stiffer for less invasive cells, and could be of importance in cancer metastasis.

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DAG–1 Carcinoma Cell in Studying the Mechanisms of Progression and Therapeutic Resistance in Bladder Cancer

Cited by 8 publications

References 19 publications

A Predictive 7-Gene Assay and Prognostic Protein Biomarkers for Non-small Cell Lung Cancer

A Predictive 7-Gene Assay and Prognostic Protein Biomarkers for Non-small Cell Lung Cancer

Maspin – the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer – is strongly expressed in preneoplastic bronchial lesions

Local mechanical properties of bladder cancer cells measured by AFM as a signature of metastatic potential

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