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.
RESUMO
In this case report we have described a patient suffering from sclerosing cholangitis, diabetes mellitus type I, and consequent end-stage renal disease who was successfully treated with simultaneous pancreas and kidney transplantation 9 years after orthotopic liver transplantation.
Assuntos
Colangite Esclerosante/cirurgia , Diabetes Mellitus Tipo 1/cirurgia , Nefropatias Diabéticas/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim , Transplante de Fígado , Transplante de Pâncreas , Adulto , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/etiologia , Substituição de Medicamentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Falência Renal Crônica/etiologia , Transplante de Rim/imunologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/imunologia , Masculino , Transplante de Pâncreas/imunologia , Fatores de Tempo , Resultado do TratamentoRESUMO
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.