1. Gamma-enolase : a well known tumour marker, with a less-known role in cancerTjaša Vižin, Janko Kos, 2015, pregledni znanstveni članek Povzetek: Gamma-enolase, known also as neuron-specific enolase (NSE), is an enzyme of the glycolytic pathway, which is expressed predominantly in neurons and cells of the neuroendocrine system. As a tumour marker it is used in diagnosis and prognosis of cancer; however, the mechanisms enrolling it in malignant progression remain elusive. As a cytoplasmic enzyme gamma-enolase is involved in increased aerobic glycolysis, the main source of energy in cancer cells, supporting cell proliferation. However, different cellular localisation at pathophysiological conditions, proposes other cellular engagements. The C-terminal part of the molecule, which is not related to glycolytic pathway, was shown to promote survival of neuronal cells by regulating neuronal growth factor receptor dependent signalling pathways, resulting also in extensive actin cytoskeleton remodelling. This additional function could be important also in cancer cells either to protect cells from stressful conditions and therapeutic agents or to promote tumour cell migration and invasion. Gamma-enolase might therefore have a multifunctional role in cancer progression: it supports increased tumour cell metabolic demands, protects tumour cells from stressful conditions and promotes their invasion and migration.
Ključne besede: gamma-enolase, cancer, glycolysis, cell survival, tumour marker
Objavljeno v DiRROS: 23.04.2024; Ogledov: 73; Prenosov: 41
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2. Carboxypeptidase cathepsin X defines a multifunctional role of gamma-enolase in cancerTjaša Vižin, Anja Pišlar, Ib Jarle Christensen, Hans Jørgen Nielsen, Pika Meško-Brguljan, Janko Kos, 2022, izvirni znanstveni članek Povzetek: Gamma-enolase enzymatic activity is involved in glycolysis, a prevalent process in cancer cell metabolism. Additionally, gamma-enolase has a pro-survival function, exhibited through the active site at the C-terminal end of the molecule. This activity is regulated by cysteine peptidase cathepsin X, which cleaves two amino acids at C-terminal end of gamma-enolase. In clinical practice, the determination of gamma-enolase as a tumour marker does not differ between total, uncleaved and C-terminally cleaved forms. However, levels of uncleaved gamma-enolase alone may provide additional clinical information. In this study we analysed cathepsin X, C- terminally uncleaved and total gamma-enolase in tumour cell lines and sera from 255 patients with colorectal cancer (CRC) by western blot, immunoprecipitation, enzymatic activity, ELISAs and ECLIA. Results show that uncleaved gamma-enolase, rather than total gamma- enolase, exhibits different levels in cells, being the highest in those, derived from metastatic sites or highly invasive tumours. Gamma-enolase is secreted into the extracellular space predominantly as an uncleaved form and levels were congruent to those within the cells. Furthermore, levels of uncleaved gamma-enolase in cells are inversely related to cathepsin X protein level and its enzymatic activity. Uncleaved gamma-enolase is also predominant form in sera of patients with CRC. Both forms exhibit similar stage dependent distribution, with slightly elevated levels in stage IV patients. Higher levels of total gamma-enolase are significantly related to shorter survival in patients with metastatic CRC. Results support evidence of additional pro-survival function of gamma-enolase in cancer. Future studies should focus on analysis of uncleaved gamma-enolase in tumour samples, which may provide additional relations to clinical indicators of disease progression.
Ključne besede: cancer, cathepsin X, cell survival, gamma-enolase, prognosis
Objavljeno v DiRROS: 06.04.2022; Ogledov: 826; Prenosov: 468
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3. PD-L1 expression can be regarded as prognostic factor for survival of non-small cell lung cancer patients after chemoradiotherapyMartina Vrankar, Matjaž Zwitter, Izidor Kern, Karmen Stanič, 2018, izvirni znanstveni članek Povzetek: The standard treatment for inoperable locally advanced non-small cell lung cancer (LA NSCLC) includes concurrent or sequential chemotherapy (ChT) and radiation therapy (RT). Long term survival rates with these approaches remains only in the order of 15%, therefore new treatment strategies, including immunotherapy, are under investigation, with programmed death ligand-1 (PD-L1) as one of the major players. We evaluated the clinical significance of PD-L1 expression in tumor samples from patients with inoperable LA NSCLC who underwent concurrent chemoradiotherapy (CRT) in our institution between 2005 and 2010 and correlated their expression with clinicopathological parameters and outcome of treatment. Among 107 patients treated with concurrent CRT, a total of 43 (36 males and 7 females) had sufficient tissue for immunohistochemical (IHC) staining. The expression of PD-L1 was demonstrated in 7 tumors, in 6 males and 1 female. No statistical significant differences in patient characteristics, including age, smoking status and gender, were found according to the PD-L1 expression. After a median follow up of 103.6 months, median progression free survival (PFS) was 19.9 months in patients without and 10.1 months in patients with PD-L1 expression (p=0.008). Median overall survival (OS) was 28.4 and 12.1 months for PD-L1 negative and PD-L1 positive patients, respectively (p=0.012). In conclusions, patients with PD-L1 expression had shorter PFS and OS after concurrent CRT in LA NSCLC. Unfortunately, only small number of patients had tissue available for the IHC testing, therefore no firm conclusions could be made and further investigation is warranted.
Ključne besede: non-small cell lung cancer, lung cancer, chemoradiotherapy, survival
Objavljeno v DiRROS: 17.12.2020; Ogledov: 1356; Prenosov: 425
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