16
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Lactate Dehydrogenase in Hepatocellular Carcinoma: Something Old, Something New

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Hepatocellular carcinoma (HCC) is the most common primary liver tumour (80–90%) and represents more than 5.7% of all cancers. Although in recent years the therapeutic options for these patients have increased, clinical results are yet unsatisfactory and the prognosis remains dismal. Clinical or molecular criteria allowing a more accurate selection of patients are in fact largely lacking. Lactic dehydrogenase (LDH) is a glycolytic key enzyme in the conversion of pyruvate to lactate under anaerobic conditions. In preclinical models, upregulation of LDH has been suggested to ensure both an efficient anaerobic/glycolytic metabolism and a reduced dependence on oxygen under hypoxic conditions in tumour cells. Data from several analyses on different tumour types seem to suggest that LDH levels may be a significant prognostic factor. The role of LDH in HCC has been investigated by different authors in heterogeneous populations of patients. It has been tested as a potential biomarker in retrospective, small, and nonfocused studies in patients undergoing surgery, transarterial chemoembolization (TACE), and systemic therapy. In the major part of these studies, high LDH serum levels seem to predict a poorer outcome. We have reviewed literature in this setting trying to resume basis for future studies validating the role of LDH in this disease.

          Related collections

          Most cited references38

          • Record: found
          • Abstract: found
          • Article: not found

          HIF-1: mediator of physiological and pathophysiological responses to hypoxia.

          All organisms can sense O(2) concentration and respond to hypoxia with adaptive changes in gene expression. The large body size of mammals necessitates the development of multiple complex physiological systems to ensure adequate O(2) delivery to all cells under normal conditions. The transcriptional regulator hypoxia-inducible factor 1 (HIF-1) is an essential mediator of O(2) homeostasis. HIF-1 is required for the establishment of key physiological systems during development and their subsequent utilization in fetal and postnatal life. HIF-1 also appears to play a key role in the pathophysiology of cancer, cardiovascular disease, and chronic lung disease, which represent the major causes of mortality among industrialized societies. Genetic or pharmacological modulation of HIF-1 activity in vivo may represent a novel therapeutic approach to these disorders.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma.

            Recent studies have shown that the prognosis of recurrent hepatocellular carcinoma (HCC) after resection was dependent on the time of recurrence. The current study investigated whether early and late intrahepatic recurrences were associated with different risk factors and prognostic factors. After curative resection of HCC, 246 patients were followed prospectively for recurrence. Intrahepatic recurrences were classified into early ( 1 year) recurrences. Risk factors for recurrence and prognostic factors for survival after recurrence in each group were analyzed. Early and late intrahepatic recurrences developed in 80 patients and 46 patients, respectively. By multivariate analysis, preoperative tumor rupture (P = 0.022) and venous invasion (P < 0.001) were independent risk factors for early recurrence, whereas cirrhosis (P = 0.018) was the only significant risk factor for late recurrence. By comparing histologic features of resected recurrent and primary tumors, 8 of 9 resected early recurrent tumors (89%) were classified as intrahepatic metastases, whereas all 6 resected late recurrent tumors (100%) were multicentric occurrences. Despite similar treatments, the prognosis for patients with early recurrence was worse than that of patients with late recurrence (median survival of 15.8 months vs. 29.6 months; P = 0.005). Independent prognostic factors for early recurrence were serum albumin level and initial tumor pTNM classification, whereas only serum bilirubin level was found to be an independent prognostic factor for late recurrence. Early and late intrahepatic recurrences after resection of HCC were associated with different risk factors and prognostic factors. Early recurrences appear to arise mainly from intrahepatic metastases, whereas late recurrences are more likely to be multicentric in origin. The current study suggests that different strategies may be needed for the prevention and management of early and late recurrences. Further studies based on genetic analysis of clonal origins of tumors are required to clarify fully the mechanism of early and late recurrences after resection of HCC. Copyright 2000 American Cancer Society.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Signal transduction to hypoxia-inducible factor 1.

              Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that functions as a master regulator of O2 homeostasis. HIF-1 target genes encode proteins that increase O2 delivery and mediate adaptive responses to O2 deprivation. HIF-1 activity is regulated by the cellular O2 concentration and by the major growth factor-stimulated signal transduction pathways. In human cancer cells, both intratumoral hypoxia and genetic alterations affecting signal transduction pathways lead to increased HIF-1 activity, which promotes angiogenesis, metabolic adaptation, and other critical aspects of tumor progression.
                Bookmark

                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2016
                29 May 2016
                : 2016
                : 7196280
                Affiliations
                1Medical Oncology Unit, Università Politecnica delle Marche, AOU “Ospedali Riuniti Umberto I-G.M. Lancisi- G. Salesi”, 60121 Ancona, Italy
                2Medical Oncology Unit, Università degli Studi di Cagliari, AOU di Cagliari, 09042 Cagliari, Italy
                3Hôpitaux Universitaires de Strasbourg, Faculté de Médecine, IRCAD/EITS, Institut Hospitalo-Universitaire de Strasbourg IHU MixSurg, Université de Strasbourg, 67100 Strasbourg, France
                4IRCCS, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, 47014 Meldola, Italy
                5Medical Oncology Unit, Università degli Studi di Modena e Reggio Emilia, 41121 Modena, Italy
                Author notes

                Academic Editor: Fumio Imazeki

                Article
                10.1155/2016/7196280
                4903134
                27314036
                e3709447-0cb6-4fb0-aa23-3fb06c2ca94c
                Copyright © 2016 Luca Faloppi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 January 2016
                : 17 April 2016
                : 5 May 2016
                Categories
                Review Article

                Comments

                Comment on this article