Blog
About

7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      AA-NAT, MT1 and MT2 Correlates with Cancer Stem-Like Cell Markers in Colorectal Cancer: Study of the Influence of Stage and p53 Status of Tumors

      Read this article at

      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

          The characterization of colon cancer stem cells (CSCs) may help to develop novel diagnostic and therapeutic procedures. p53 loss increases the pool of CSCs in colorectal cancer (CRC). Recent reports suggest that the oncostatic effects of melatonin could be related to its ability to kill CSCs. Although there are no data linking the loss of p53 function and melatonin synthesis or signaling in cancer, melatonin does activate the p53 tumor-suppressor pathway in this disease. In this work, we analyze whether the expression of melatonin synthesis and signaling genes are related to the expression of CSC markers and the implication of p53 status in samples from patients with CRC. Arylalkylamine N-acetyltransferase (AA-NAT), MT1, and MT2 expression decreased in tumor samples versus normal mucosa samples in mutated p53 (mtp53) tumors versus those with wild-type p53 (wtp53). Further, AA-NAT and MT2 expression were lower in advanced stages of the disease in wtp53 tumors. On the contrary, CD44 and CD66c expression was higher in tumor versus normal mucosa in wtp53 tumors. Additionally, CD44 expression was higher in advanced stages of the disease regardless of the p53 status. Patients with CD44 highCD66c high and wtp53 tumors in advanced stages showed low expression of AA-NAT and MT2 in wtp53 tumors. These results could indicate a possible interaction of these pathways in CRC.

          Related collections

          Most cited references 67

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

          Identification and expansion of human colon-cancer-initiating cells.

          Colon carcinoma is the second most common cause of death from cancer. The isolation and characterization of tumorigenic colon cancer cells may help to devise novel diagnostic and therapeutic procedures. Although there is increasing evidence that a rare population of undifferentiated cells is responsible for tumour formation and maintenance, this has not been explored for colorectal cancer. Here, we show that tumorigenic cells in colon cancer are included in the high-density CD133+ population, which accounts for about 2.5% of the tumour cells. Subcutaneous injection of colon cancer CD133+ cells readily reproduced the original tumour in immunodeficient mice, whereas CD133- cells did not form tumours. Such tumours were serially transplanted for several generations, in each of which we observed progressively faster tumour growth without significant phenotypic alterations. Unlike CD133- cells, CD133+ colon cancer cells grew exponentially for more than one year in vitro as undifferentiated tumour spheres in serum-free medium, maintaining the ability to engraft and reproduce the same morphological and antigenic pattern of the original tumour. We conclude that colorectal cancer is created and propagated by a small number of undifferentiated tumorigenic CD133+ cells, which should therefore be the target of future therapies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors.

            In this article, the incidence, mortality, and survival rates for colorectal cancer are reviewed, with attention paid to regional variations and changes over time. A concise overview of known risk factors associated with colorectal cancer is provided, including familial and hereditary factors, as well as environmental lifestyle-related risk factors such as physical inactivity, obesity, smoking, and alcohol consumption.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Colorectal cancer.

              Substantial progress has been made in colorectal cancer in the past decade. Screening, used to identify individuals at an early stage, has improved outcome. There is greater understanding of the genetic basis of inherited colorectal cancer and identification of patients at risk. Optimisation of surgery for patients with localised disease has had a major effect on survival at 5 years and 10 years. For rectal cancer, identification of patients at greatest risk of local failure is important in the selection of patients for preoperative chemoradiation, a strategy proven to improve outcomes in these patients. Stringent postoperative follow-up helps the early identification of potentially radically treatable oligometastatic disease and improves long-term survival. Treatment with adjuvant fluoropyrimidine for colon and rectal cancers further improves survival, more so in stage III than in stage II disease, and oxaliplatin-based combination chemotherapy is now routinely used for stage III disease, although efficacy must be carefully balanced against toxicity. In stage II disease, molecular markers such as microsatellite instability might help select patients for treatment. The integration of targeted treatments with conventional cytotoxic drugs has expanded the treatment of metastatic disease resulting in incremental survival gains. However, biomarker development is essential to aid selection of patients likely to respond to therapy, thereby rationalising treatments and improving outcomes. Copyright 2010 Elsevier Ltd. All rights reserved.
                Bookmark

                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                11 June 2017
                June 2017
                : 18
                : 6
                Affiliations
                [1 ]Biosanitary Research Institute, ibs.Granada, 18012 Granada, Spain; jorgecasado@ 123456ugr.es (J.C.); sergiojr_84@ 123456hotmail.com (S.M.J.-R.); sandrariosarrabal@ 123456hotmail.com (S.R.-A.); angel_carazo@ 123456yahoo.es (Á.C.-G.); isabeln@ 123456ugr.es (M.I.N.); arextrem@ 123456ugr.es (Á.R.-E.); fsalmero@ 123456ugr.es (J.S.)
                [2 ]Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, 18012 Granada, Spain; alinch.2005@ 123456gmail.com
                [3 ]Department of Radiology and Physical Medicine, University of Granada, 18012 Granada, Spain
                [4 ]General Surgery Unit, San Cecilio University Hospital, 18012 Granada, Spain; crisgona2@ 123456hotmail.com
                [5 ]Ciber of Hepatic and Digestive Diseases (CIBERehd), Biosanitary Research Institute, ibs.Granada, 18012 Granada, Spain
                [6 ]Pediatric Unit, Granada University and San Cecilio University Hospital, 18012 Granada, Spain
                Author notes
                [* ]Correspondence: pepileon@ 123456ugr.es ; Tel.: +34-958-023-706
                [†]

                These authors contribute equally to this work.

                ijms-18-01251
                10.3390/ijms18061251
                5486074
                28604612
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Categories
                Article

                Molecular biology

                metastasis, colorectal cancer, melatonin, cancer stem cells, p53

                Comments

                Comment on this article