Hypoxia-Related Proteins in Patients With Rectal Cancer Undergoing Neoadjuvant Combined Modality Therapy

Lee-Kong, Steven A.; Ruby, Jeannine A.; Chessin, David B.; Pucciarelli, Salvatore; Shia, Jinru; Riedel, Elyn; Nitti, Donato; Guillem, José G.

doi:10.1097/dcr.0b013e31825bd80c

Cited by 22 publications

(13 citation statements)

References 38 publications

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“…Elevated CA IX expression is associated with poorer overall survival in locally advanced rectal cancer treated by neoadjuvant chemoradiation and resection [122]. More recent studies extend this evidence for non-small cell lung cancer, where CA IX expression predicts shorter time to relapse, correlates with tumor size, markers of tumor proliferation and necrosis, and tumor genetic characteristics [123].…”

Section: Ca IX Distribution In Tumors and Correlations With Clinical mentioning

confidence: 91%

Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: From biology to clinical use

Pastorek

Pastoreková

2015

Seminars in Cancer Biology

269

230

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Section: Ca IX Distribution In Tumors and Correlations With Clinical mentioning

confidence: 91%

Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: From biology to clinical use

Pastorek

Pastoreková

2015

Seminars in Cancer Biology

269

230

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“…However, SDF-1α had an association with PlGF (P=0.005). Although HIF-1α expression is known to drive expression of downstream proteins, dif ferences in individual protein half-lives may not allow for a direct relationship between HIF-1α and other proteins (37). Downstream pro teins may have been influenced by other signaling pathways independent of HIF-1α, making their expression levels somewhat variable in relation to HIF-1α.…”

Section: Tumour Responsementioning

confidence: 99%

Upregulation of stromal cell-derived factor 1α expression is associated with the resistance to neoadjuvant chemoradiotherapy of locally advanced rectal cancer: Angiogenic markers of neoadjuvant chemoradiation

et al. 2014

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Abstract. The ability to achieve pathologic downstaging after neoadjuvant chemoradiotherapy (NCRT) is correlated with improved survival in locally advanced rectal cancer (LARC). However, there is no effective predictive markers. In this study, the expression of angiogenic markers was evaluated in pretreatment biopsies and corresponding post-treatment resection specimens, and were correlated to histopathological tumour characteristics and response. Fifty-five patients with stage II/III rectal cancer treated with 5-fluorouracil (5-FU)-based NCRT were studied. All patients were administered NCRT followed by surgical resection. Immunohistochemical staining for angiogenic markers [hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor 1α (SDF-1α) and placental growth factor (PlGF)] was performed on specimens obtained before NCRT and after surgery. Expression of VEGF, PlGF and HIF-1α protein was downregulated after NCRT in the rectal cancer tissues (P<0.001, P=0.001 and P=0.044, respectively). However, SDF-1α was upregulated after NCRT (P<0.001). Moreover, upregulated expression of SDF-1α (P=0.016) and positive PlGF staining (P= 0.001) after NCRT were significantly associated with resistance to NCRT. On multivariate analysis, positive PlGF staining after NCRT was found to be independently associated with resistance to NCRT (P=0.013).Our data suggest that SDF-1α and PlGF should be evaluated as new targets for NCRT in LARC.

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“…Such variability results in unpredictable tumor responses and host toxicity. Hence, our study investigated the role of the genetic expression levels of 6 fluoropyrimidine-based chemotherapy-related genes ( DPYD , TYMS , TYMP , thymidine kinase 1, soluble ( TK1 ), thymidine kinase 2, mitochondrial ( TK2 ), and orotate phosphoribosyl transferase ( ORPT )) and 3 genes related to radiotherapy (RT) response (glucose transporter member 1 ( GLUT1 ), hypoxia-inducible factor 1 ( HIF1 ), and hypoxia-inducible factor 2 ( HIF2 )) in the literature, genomic databases, and the Medline database [22–28]. …”

Section: Introductionmentioning

confidence: 99%

DPYD,TYMS,TYMP,TK1, andTK2Genetic Expressions as Response Markers in Locally Advanced Rectal Cancer Patients Treated with Fluoropyrimidine-Based Chemoradiotherapy

Huang

Chung

et al. 2013

BioMed Research International

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This study is to investigate multiple chemotherapeutic agent- and radiation-related genetic biomarkers in locally advanced rectal cancer (LARC) patients following fluoropyrimidine-based concurrent chemoradiotherapy (CCRT) for response prediction. We initially selected 6 fluoropyrimidine metabolism-related genes (DPYD, ORPT, TYMS, TYMP, TK1, and TK2) and 3 radiotherapy response-related genes (GLUT1, HIF-1 α, and HIF-2 α) as targets for gene expression identification in 60 LARC cancer specimens. Subsequently, a high-sensitivity weighted enzymatic chip array was designed and constructed to predict responses following CCRT. After CCRT, 39 of 60 (65%) LARC patients were classified as responders (pathological tumor regression grade 2 ~ 4). Using a panel of multiple genetic biomarkers (chip), including DPYD, TYMS, TYMP, TK1, and TK2, at a cutoff value for 3 positive genes, a sensitivity of 89.7% and a specificity of 81% were obtained (AUC: 0.915; 95% CI: 0.840–0.991). Negative chip results were significantly correlated to poor CCRT responses (TRG 0-1) (P = 0.014, hazard ratio: 22.704, 95% CI: 3.055–235.448 in multivariate analysis). Disease-free survival analysis showed significantly better survival rate in patients with positive chip results (P = 0.0001). We suggest that a chip including DPYD, TYMS, TYMP, TK1, and TK2 genes is a potential tool to predict response in LARC following fluoropyrimidine-based CCRT.

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Hypoxia-Related Proteins in Patients With Rectal Cancer Undergoing Neoadjuvant Combined Modality Therapy

Cited by 22 publications

References 38 publications

Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: From biology to clinical use

Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: From biology to clinical use

Upregulation of stromal cell-derived factor 1α expression is associated with the resistance to neoadjuvant chemoradiotherapy of locally advanced rectal cancer: Angiogenic markers of neoadjuvant chemoradiation

DPYD,TYMS,TYMP,TK1, andTK2Genetic Expressions as Response Markers in Locally Advanced Rectal Cancer Patients Treated with Fluoropyrimidine-Based Chemoradiotherapy

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