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1.
Eur Surg ; 48(6): 352-356, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28058043

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the fourth most common cause of death worldwide. Approximately 30 % of all CRC occurs in the rectum. Improvements in survival rates were achieved thanks to multimodal therapy, combining surgery and chemoradiation. Nevertheless, the prognosis of patients suffering from rectal cancer (RC) remains poor. Programmed cell death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) regulate tumor immune response. The aim of this study was to analyze the expression of PD-L1 in RC pre- and post-neoadjuvant therapy and evaluate PD-L1 as a biomarker and potential target for therapy. METHODS: In all, 29 patients with RC treated at the Medical University Vienna who received preoperative chemoradiation were retrospectively enrolled in this study. Expression of PD-L1 was investigated by immunohistochemistry with two different anti-PD-L1 antibodies. RESULTS: No PD-L1 expression on cancer cells could be observed in all 29 cases in the specimens before chemoradiation as well as in the surgical specimens after neoadjuvant therapy. In one of the two staining methods performed, five (17.24 %) post-chemoradiation cases showed faint lymphohistiocytic staining. CONCLUSION: No expression of PD-L1 in RC cells before and after chemoradiation was found in our collective of 29 patients. Further investigations to evaluate the role of PD-L1 as a potential therapeutic target in RC are urgently needed.

3.
Br J Surg ; 96(7): 809-16, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19526622

RESUMO

BACKGROUND: Studies using phosphorus magnetic resonance spectroscopy (MRS) have pointed to the significance of phospholipid metabolite alterations as biochemical markers for tumour progression or therapy response. METHODS: Spectroscopic imaging was performed in colorectal flank tumours in nude mice. In vivo tumour doubling times for each cell line were measured. In vivo sensitivity of each tumour line to treatment with G207 and NV1020 oncolytic viruses was assessed. Correlations between viral sensitivity and tumour doubling time and phosphorus MRS were estimated. RESULTS: For G207 virus, in vitro cytotoxicity tests showed cell viability at multiplicities of infection (ratio of viral particles per tumour cell) of 0.1 on day 6 as follows: C85, less than 1 per cent; HCT8, 1 per cent; LS174T, 9 per cent; HT29, 18 per cent; and C18, 92 per cent. Respective values for NV1020 were 1, 18, 4, 18 and 86 per cent. The phosphoethanolamine to phosphocholine ratio was significantly lower in virus-sensitive than -insensitive cells, and was dependent on tumour doubling time. CONCLUSION: Alterations in membrane phospholipid metabolites that relate to proliferation of cancer cells affect the efficacy of oncolytic viral therapy. MRS proved a highly sensitive non-invasive tool for predicting the efficacy of viruses.


Assuntos
Neoplasias Colorretais/terapia , Escherichia coli/metabolismo , Herpesvirus Humano 1/metabolismo , Terapia Viral Oncolítica , Fosfolipídeos/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Vetores Genéticos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Isótopos de Fósforo , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Transfecção , Transplante Heterólogo
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