DSpace Collection:https://hdl.handle.net/10171/122062024-03-29T05:15:04Z2024-03-29T05:15:04ZChallenges and novel opportunities of radiation therapy for brain metastases in non-small cell lung cancerhttps://hdl.handle.net/10171/628492024-02-12T08:47:12Z2021-01-01T00:00:00ZTitle: Challenges and novel opportunities of radiation therapy for brain metastases in non-small cell lung cancer
Abstract: Lung cancer is the most common primary malignancy that tends to metastasize to the brain. Owing to improved survival of lung cancer patients, the prevalence of brain metastases is a matter of growing concern. Brain radiotherapy remains the mainstay in the management of metastatic CNS disease. However, new targeted therapies such as the tyrosine kinase or immune checkpoint inhibitors have demonstrated intracranial activity and promising tumor response rates. Here, we review the current and emerging therapeutical strategies for brain metastases from non-small cell lung cancer, both brain-directed and systemic, as well as the uncertainties that may arise from their combination.2021-01-01T00:00:00ZHeterogenous presence of neutrophil extracellular traps in human solid tumours is partially dependent on IL-8https://hdl.handle.net/10171/620042024-02-08T13:51:45Z2021-01-01T00:00:00ZTitle: Heterogenous presence of neutrophil extracellular traps in human solid tumours is partially dependent on IL-8
Abstract: Neutrophil extracellular traps (NETs) are webs of extracellular nuclear DNA extruded by dying neutrophils infiltrating
tissue. NETs constitute a defence mechanism to entrap and kill fungi and bacteria. Tumours induce the formation of
NETs to the advantage of the malignancy via a variety of mechanisms shown in mouse models. Here, we investigated
the presence of NETs in a variety of human solid tumours and their association with IL-8 (CXCL8) protein expression
and CD8+ T-cell density in the tumour microenvironment. Multiplex immunofluorescence panels were developed to
identify NETs in human cancer tissues by co-staining with the granulocyte marker CD15, the neutrophil marker myeloperoxidase
and citrullinated histone H3 (H3Cit), as well as IL-8 protein and CD8+ T cells. Three ELISA methods to
detect and quantify circulating NETs in serum were optimised and utilised. Whole tumour sections and tissue microarrays
from patients with non-small cell lung cancer (NSCLC; n = 14), bladder cancer (n = 14), melanoma (n = 11),
breast cancer (n = 31), colorectal cancer (n = 20) and mesothelioma (n = 61) were studied. Also, serum samples
collected retrospectively from patients with metastatic melanoma (n = 12) and NSCLC (n = 34) were ELISA assayed
to quantify circulating NETs and IL-8. NETs were detected in six different human cancer types with wide individual
variation in terms of tissue density and distribution. At least in NSCLC, bladder cancer and metastatic melanoma, NET
density positively correlated with IL-8 protein expression and inversely correlated with CD8+ T-cell densities. In a
series of serum samples from melanoma and NSCLC patients, a positive correlation between circulating NETs and
IL-8 was found. In conclusion, NETs are detectable in formalin-fixed human biopsy samples from solid tumours
and in the circulation of cancer patients with a considerable degree of individual variation. NETs show a positive
association with IL-8 and a trend towards a negative association with CD8+ tumour-infiltrating lymphocytes.2021-01-01T00:00:00Z