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Journal of Cancer Research and Clinical Oncology

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06.04.2020 | Original Article – Cancer Research

Expression of pro-angiogenic factors as potential biomarkers in experimental models of colon cancer

verfasst von: Simona Delle Monache, Alessio Cortellini, Alessandro Parisi, Fanny Pulcini, Stefano Martellucci, Cecilia Mei, Maria Enrica Danubio, Vincenzo Mattei, Adriano Angelucci, Corrado Ficorella

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 6/2020

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Abstract

Purpose

RAS mutational status in colorectal cancer (CRC) represents a predictive biomarker of response to anti-EGFR therapy, but to date it cannot be considered an appropriate biomarker of response to anti-VEGF therapy. To elucidate the function of K-Ras in promoting angiogenesis, the effect of conditioned media from KRAS mutated and wild type colon cancer cell lines on HUVECs tubule formation ability and the correspondent production of pro-angiogenic factors have been evaluated by a specific ELISA assay.

Methods

Ras-activated signaling pathways were compared by western blot analysis and RTq-PCR. In addition, VEGF, IL-8, bFGF and HIF-1α expression was determined in K-RAS silenced cells. Furthermore, we conducted an observational study in a cohort of RAS mutated metastatic CRC patients, treated with first-line bevacizumab-based regimens, evaluating VEGF-A and IL-8 plasma levels at baseline, and during treatment.

Results

K-RAS promotes VEGF production by cancer cell lines. At the transcriptional level, this is reflected to a K-RAS dependent HIF-1α over-expression. Moreover, the HIF-1α, VEGF and FGF expression inhibition in KRAS knocked cells confirmed these results. Within the clinical part, no statistically significant correlation has been found between progression-free survival (PFS) and VEGF-A/IL-8 levels, but we cannot exclude that these biomarkers could be further investigated as predictive or prognostic biomarkers in this setting.

Conclusion

Our study confirmed the direct involvement of K-Ras in promoting angiogenesis into colon cancer cell lines.

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Titel: Expression of pro-angiogenic factors as potential biomarkers in experimental models of colon cancer
verfasst von: Simona Delle Monache
Alessio Cortellini
Alessandro Parisi
Fanny Pulcini
Stefano Martellucci
Cecilia Mei
Maria Enrica Danubio
Vincenzo Mattei
Adriano Angelucci
Corrado Ficorella
Publikationsdatum: 06.04.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 6/2020
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03186-x

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Expression of pro-angiogenic factors as potential biomarkers in experimental models of colon cancer

Abstract

Purpose

Methods

Results

Conclusion

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Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

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Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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