International Journal of Genetics and Genomics

| Peer-Reviewed |

Lymphocyte Reproductive Activity Normalized to Numbers of Hematopoietic Stem Cells in Blood and Rate of Death in Fatal Diseases

Received: 29 January 2017    Accepted: 13 February 2017    Published: 18 October 2017
Views:       Downloads:

Share This Article

Abstract

The numbers of CD133+ and CD31+ lymphocytes and those in the G2-M phases in the total fraction of circulating lymphocytes from patients with fatal liver cirrhosis and advanced lung cancer were investigated by flow cytometry during a long period of conventional treatment with OLT or palliative surgery followed by myelosuppressive chemotherapy. The relationships of specific reproductive activity, sRA (G2-M/CD133+), and the number of committed liver α-fetoprotein-positive (AFP+) cells with the rate of patient deaths, characterized by exponential approximation survival curves for both diseases, were investigated. Subnormal sRA in patients after OLT and excessive sRA in LC patients above a healthy level were associated with higher death rates and lower survival, coinciding with strong immunosuppression caused by anti-rejection and anti-cancer therapies. These findings may be explained by morphogenesis (feeding) activity of circulating lymphocytes targeted toward both normal and malignant tissues rather than in terms of cellular immunity. The sRA changes may be a useful indicator for monitoring the potential for engraftment or tumor growth.

DOI 10.11648/j.ijgg.20170505.12
Published in International Journal of Genetics and Genomics (Volume 5, Issue 5, October 2017)
Page(s) 54-62
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Hematopoietic Stem Cells, Lymphocytes, Specific Reproductive Activity, Resource of Lymphopoiesis, Lung Cancer Therapy, Liver Transplantation, Death Rate

References
[1] M. Kucia, J. Ratajczak, and MZ. Ratajczak, Bone marrow as a source of circulating CXCR4+tissue- committed stem cells, Biol Cell, vol. 97 (2), pp. 133-146, February 2005. doi:10.1042/BC20040069.
[2] Ch. Drapeau, Cracking the stem cell code: demystifying the most dramatic scientific breakthrough of our times. Hillsboro, Or, Goodwill Books USA, Sutton Hart Press/1st ed. 2010. http://www.amazon.com/Cracing-Stem-Cell-Code-Miraculous/dp/098102095X.
[3] A. N. Shoutko, O. A. Gerasimova, L. P. Ekimova, F. K. Zherebtsov V. F. Mus, D. A. Granov, and A. M. Granov, Long -term activation of circulating liver-committed mononuclear cells after OLT, J J Regener Med, vol. 1 (3), pp.011, March 2016. http://regenerativemedicine.jacobspublishers.com/images/Regenarative/J_J_Regener_Med_1_3_011.pdf.
[4] A. Shoutko, L. Ekimova, V. Mus, and V. Sokurenko, Fluctuations of CD34 cells number in blood of cancer patients during final year of life, Medical and Health Science Journal (MHSJ), 2012. vol.13 (4), pp.7-13, January 2012. doi: http://dx.doi.org/10.15208/mhsj.2012.52.
[5] B.-S. Ding, D. James, R. Iyer, I. Falciatori, D. Hambardzumyan, Su Wang, J. M. Butler, S. Y. Rabbany, and A.Hormigo, Prominin 1/CD133 endothelium sustains growth of proneural glioma, PloS ONE, vol. 8 (4), pp. e62150, April 2013. doi:10.1371/journal.pone.0062150.
[6] I. Colmegna, A. Diaz-Borjon, H. Fujii, L. Schaefer, J. J. Goronzy, and C M. Weyand, Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in rheumatoid arthritis, Arthritis Rheum, vol. 58 (4),pp. 990-1000. April 2008. doi: 10.1002/art.23287.
[7] G. Van Zant, and Ying Liang, Concise Review: Hematopoietic stem cell aging, life span, and transplantation, Stem Cells Transplantational Medicine, vol.1 (9), pp. 651–657, September 2012.doi:10 5966/sctm.2012-0033.
[8] H. Silva, and I. M. Conboy, Aging and stem cell renewal, in: Stem Book,internet, L. Girard, Ed., Harvard Stem Cell Institute, Harvard University, July, 2008. PMID: 20614587: doi: 10.3824/stembook.1.11.1 doi/10.3824/stembook.1.11.1,
[9] A. N. Shoutko, and L. P. Ekimova. The impact of middle age on the viability of patients with nonmalignant and malignant diseases. Cancer Research Journal, vol. 2 (6), pp. 114-120, December 2014. doi: 10.11648/j.crj.20140206.14 10.
[10] L. Chen, Y. Lou, Y. Chen, and J. Yang, Prognostic value of the neutrophil-to-lymphocyte ratio inpatients with acute-on-chronic liver failure, Int J Clin Pract, 68 (8), pp. 1034–1040, August 2014. doi: 10.1111/ijcp.12408.
[11] A. M. Granov, D. A. Granov, F. K. Zherebtsov, O. A. Gerasimova, V. V. Borovik, V. V. Osovskikh, D. N. Maystrenko, I. O. Rutkin, S. P. Tsurupa, I. I. Tileubergenov, S. V. Shapoval, and T. G. Mikhaylichenko, Livertransplantation. A single center experience of 100 cases, Vestnik transplantologii I iskusstvennich organov, vol. 14 (4), pp.11-16, December 2012 journal.transpl.ru›.
[12] Curve fitting project - pdf.io, pp. 1-4. dynsys.uml.edu/tutorials/Regression.../curve_fit_proj_101905.pdf.
[13] Sh. S. Eaker, T. S. Hawley, A. Ramezani, and R. G. Hawley, Detection and enrichment of hematopoietic stem cells by side population phenotype, in: Methods in molecular biology: flow cytometry protocols, 2nd ed., T. S. Hawley and R. G. Hawley Eds., © Humana Press Inc., Totowa, NJ, 2004, pp161-180. https://flowcytometry.gwu.edu/.../flowcytometry.../fcp9.pdf.
[14] I. Sales-Pardo, A. Avendaño, V. Martinez-Muñoz, M. García-Escarp, R. Celis, Ph. Whittle, J. Barquinero, J. C. Domingo, P. Marin, and J. Petriz, Flow cytometry of the side population: tips& tricks, Cellular oncology, vol. 28 (1-2), pp. 37–53, January 2006. http://dx.doi.org/10.1155/2006/536519.
[15] St. L. Nelson, Statistical formulas in Excel. stephenlnelson.com/articles/statistical-formulas-in-excel/.
[16] J. L. Loveland,. Mathematical justification of introductory hypothesis tests and development of reference Materials, (report for M. Sc. “Mathematics”). Utah State University, 2011, Retrieved April/2013. digitalcommons.usu.edu›...› GRADREPORTS› 14.
[17] A. Medkhaly, E. Simoneau, S. Doi, P. Metrakos, and M. Hassanain, Developing a prognostic score for early prediction of graft and patient survival after orthotopic liver transplantation Am J Transplant, 2013; 13 (suppl 5). http://www.atcmeetingabstracts.com/abstract/developing-a-prognostic-score-for-early-prediction-of-graft-and-patient-survival-after-orthotopic-liver-transplantation/.
[18] Lee S-G, Hwang Sh, LeeY-J, Park K-M, Jeon H-B, Min PCh. Regeneration of graft liver in adult-to-adult living donor liver transplantation using a left lobe graft. J. Korean Med. Sci. vol. 13 (4), pp. 350–354, August 1998. https://uic.pure.elsevier.com/.../regeneration-of-graft-liver-in.
[19] A. Jain, J. Reyes, R. Kashyap, S. F. Dodson, A. J. Demetris, K. Ruppert, K. Abu-Elmagd, W. Marsh, J. Madariaga, G. Mazariegos, D. Geller, C. A. Bonham, T. Gayowski, T. Cacciarelli, P. Fontes, T. E. Starzl, and J. J. Fung, Long-term survival after liver transplantation in 4,000 consecutive patients at single center, Ann Surg, vol. 232 (4), pp. 490–500 October 2000. PMC1421181.
[20] A. Ekka-Zochar, Y. Zitser-Gurevich, M. Mandel, I. Weiss-Salz, S. Nir, E. Mor, N. Richard, H. Merhav, R. Bruck, and E. Simchen, Graft survival and its determinants: a 3 year national experience with liver transplantation in Israel. IMAJ, vol.8 (6), pp.400–405, Dec. 2006. PMID: 16833169.
[21] Zhong Li, CD133: a stem cell biomarker and beyond, Exp Hematol Oncol, 2 (17) July 2013.doi: 10.1186/2162-3619-2-17.
[22] P. G. Bertolino, W. D. Mc Caughan, and G. Bowen, Role of primary intrahepatic T-cell activation in the ‘liver tolerance effect’, Immunology and Cell Biology, vol.80, pp.4–92, October2002. doi:10.1046/j.0818-9641.2001.01048.x.
[23] R. Turner, O. Lozoya, Y. Wang, V. Cardinale, E. Gaudio, G. Alpini, G. Mendel, E. Wauthier, C. Barbier, D. Alvaro, and L. M. Reid, Human hepatic stem cell and maturation liver lineage biology, Hepatology, vol. 53 (3), pp.1035-1045, March 2011. PMID: 21374667, doi: 10.1002/hep.24157.
[24] Y. Haruna, K. Saito, S. Spaulding, M. A. Nalesnik, and M. A. Gerber, Identification of bipotential progenitor cells in human liver development, Hepatology, vol. 23 (3), pp. 476-481, March 1996. PMID: 8617427, doi: 10.1002/hep.510230312.
[25] O. D. Liang, T. Korff, J. Eckhardt, J. Rifaat, N. Baal, F. Herr, K. T. Preissner, and M. Zygmunt, Oncodevelopmental alpha-fetoprotein acts as a selective proangiogenic factor on endothelial cell from the fetomaternal unit. J Clin Endocrinol Metab, vol.89 (3), pp. 1415-22, March 2004. doi: https://doi.org/10.1210/jc.2003-031721.
[26] S. Schwartzenberg, A. Mor, G. Luboshits, D. Planer, V. G. Deutsch, G. Keren, and J. Georgeet, Association between circulating early endothelial progenitors and CD4+CD25+regulatory T-cells: a possible cross-talk between immunity and angiogenesis? Am J Immunol, vol.1 (4), pp. 143–147, 2005. thescipub.com/html/10.3844/ajisp.2005.143.147.
[27] M. Romano, F. De Francesco, G. Pirozzi, E. Gringeri, R. Boetto, M. Di Domenico, B. Zavan, G A. Ferraro, and U. Cillo, Expression of cancer stem cell biomarkers as a tool for a correct therapeutic approach to hepatocellular carcinoma, Oncoscience, vol. 2 (5) pp. 443-456, doi: 10.18632/oncoscience.163, PMC4468330.
[28] J. Hur, H.-M. Yang, Ch.-H. Yoon, Ch.-S. Lee, K.-W. Park, J.-H. Kim, T.-Y. Kim, J.-Y. Kim, H.-J. Kang, I.-H. Chae, B.-H. Oh, Y.-B. Park, and H.-S. Kim, Identification of a novel role of T-cells in postnatal vasculogenesis, Circulation, vol.116 (15) pp. 1671–1682, October 2007. PDF https://doi.org/10.1161/CIRCULATIONAHA.107.694778.
[29] Wenbo Meng, Xun Li, Zhongtian Bai, Yan Li, Jinqiu Yuan, Tao Liu, Jun Yan, Wence Zhou, Kexiang Zhu, Hui Zhang, and Yumin Li, Silencing alpha-fetoprotein inhibits VEGF and MMP-2/9 production in human hepatocellular carcinoma cell. PLoS ONE, 9 (2), pp. e90660, February 2014. http://dx.doi.org/10.1371/journal.pone.0090660.
[30] E. Arias, United States Life Tables, 2006, in: National vital statistics reports from U.S. Department of health and human services centers for disease control and prevention, National center for health statistics, National vital Statistics System, vol. 58 (21), pp.1-40, June 2010. https://www.cdc.gov/nchs/data/nvsr/nvsr58/nvsr58_21.pdf.
[31] K. Billups, J. Neal, and J. Salyer, Immunosuppressant-driven de novo malignant neoplasms after solid-organ transplant, Progress in Transplantation, vol. 25 (2), pp. 182-188, June 2015. doi: http://dx.doi.org/10.7182/pit2015826.
[32] Karynsa Cetin, David S Ettinger, Yong-jiang Hei, and C. D. O’Malley, Survival by histologic subtype in stage IV nonsmall cell lung cancer based on data from the Surveillance, Epidemiology and End Results, Program Clinical Epidemiology, vol. 3, pp.139–148, April 2011. DOI: 10.2147/CLEP.S17191.
[33] 32 J. Baba, S. Watanabe, Y. Saida, T. Tanaka, T. Miyabayash, J. Koshio, K. Ichikawa, K. Nozaki, T. Koya, K. Deguchi, C. Tan, S. Miura, H. Tanaka, J. Tanaka, H. Kagamu, H.Yoshizawa, K. Nakata, and I. Narita, Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphocytopenia, Blood, vol.120 (12),pp.2417-2427 July 2012. PMID: 22806892 doi: 10.1182/blood-2012-02-411124.
[34] U.S. Department of health and human services, National institute of health, National cancer Institute,”Blood/bone marrow,” in: Common terminology criteria for adverse events (CTCAE)/Version 3.0, AMGEN Oncology, p.4, August 2006. ctep.cancer.gov/.../electronic.../ctcaev3.pdf.
[35] K. S. Tewari, J. J. Java, T. A. Gatcliffe, M. A. Bookman, and B. J. Monk, Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: an exploratory study of the gynecologic oncology group, Gynecol Oncol, vol.133 (3), pp.439-445. March 2014. doi: 10.1016/j.ygyno.2014.03.013.
[36] Z. Su, Y.-P. Mao, P.-Y. Ou Yang, J. Tang, X.-W. Lan, and F.-Y. Xie, Leucopenia and treatment efficacy in advanced nasopharyngeal carcinoma, BMC Cancer, vol.15, pp. 429. May 2015. doi:10.1186/s12885-015-1442-3.
[37] A. Shoutko, L. Yurkova, K. Borodulya, and L. Ekimova, Lymphocytopenia and cytotoxic therapy in patients with advanced ovarian cancer, Cancer Research J, 3 (3), pp. 47-51, May 2015. doi:10.11648/j.crj.20150303.11.
[38] W. W. Pang, E. A. Price, D. Sahoo, I. Beerman, W. J. Maloney, D. J. Rossi, S. L. Schrier, and I. L. Weissman, Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age, PNAS USA, vol.108, pp.20012–20017, June 2011. doi: 10.1073/pnas.1116110108.
[39] A. N. Shoutko, and L. P. Ekimova Lymphocytopenia can contribute in common benefit of cytotoxic therapy of cancer, "Inter-Medical", vol.3,pp. 5-13, 2014. www.inter-medical.ru/.../78-lymphocytopenia-can-contribute-in-common-.
[40] A. Shoutko, L. Yurkova, K. Borodulya, and L. Ekimova, Protracted half-body irradiation instead of chemotherapy: life span and lymphocytopenia in relapsed ovarian cancer, Int J of Tumor Therapy, 5 (1), pp.1-7, Feb 2016. doi: 10.5923/j.ijtt.20160501.01.
[41] A. N. Shoutko, and L. P. Ekimova Abnormal tissue proliferation and life span variability in chronically irradiated dogs, Radiat Environ Biophys, vol.53 (1), pp.65-72, March 2014. PMID: 24310526: doi: 10.1007/s00411-013-0504-7.
[42] A. D. Hayward, I. Nenko, and V. Lummaa, Early-life reproduction is associated with increased mortality risk but enhanced lifetime fitness in pre-industrial humans Proc. R. Soc. B: Biological Sciencesss, vol.282(1804), pp. 20143053. March 2015. doi: 10.1098/rspb.2014.3053; http://dx.doi.org/10.1098/rspb.2014.3053.
[43] WHO Recommendations for prevention and treatment of pre-eclampsia and eclampsia. Geneva: World Health Organization, Background 1, Bookshelf ID: NBK1405632011, National Center for Biotechnology Information, U.S. National Library of Medicine 8600 Rockville Pike, Bethesda MD, 20894 USA. https://www.ncbi.nlm.nih.gov/books/NBK140563/.
[44] P, Luppi, R. W. Powers, V. Verma, L. Edmunds, D. Plymire, and C. A. Hubel, Maternal circulating CD34+VEGFR-2+ and CD133+ VEGFR-2+ progenitor cells increase during normal pregnancy but are reduced in women with preeclampsia, Reprod Sci, vol. 17 (7), pp. 643–652, July 2010. doi: 10.1177/1933719110366164, www.ncbi.nlm.nih.gov/pmc/...; PMC2893245.
Author Information
  • Laboratory for Improvement of the Treatment Methods, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia

  • Transplantation Division, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia

  • Laboratory for Improvement of the Treatment Methods, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia

  • Transplantation Division, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia

  • Group for Lung Cancer Treatment, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia

  • Laboratory for Improvement of the Treatment Methods, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia

  • Transplantation Division, Federal Research Center for Radiology and Surgical Technologies, Saint-Petersburg, Russia

Cite This Article
  • APA Style

    Aleksei N. Shoutko, Olga A. Gerasimova, Ludmila P. Ekimova, Fiodor Zherebtsov, Viktor F. Mus, et al. (2017). Lymphocyte Reproductive Activity Normalized to Numbers of Hematopoietic Stem Cells in Blood and Rate of Death in Fatal Diseases. International Journal of Genetics and Genomics, 5(5), 54-62. https://doi.org/10.11648/j.ijgg.20170505.12

    Copy | Download

    ACS Style

    Aleksei N. Shoutko; Olga A. Gerasimova; Ludmila P. Ekimova; Fiodor Zherebtsov; Viktor F. Mus, et al. Lymphocyte Reproductive Activity Normalized to Numbers of Hematopoietic Stem Cells in Blood and Rate of Death in Fatal Diseases. Int. J. Genet. Genomics 2017, 5(5), 54-62. doi: 10.11648/j.ijgg.20170505.12

    Copy | Download

    AMA Style

    Aleksei N. Shoutko, Olga A. Gerasimova, Ludmila P. Ekimova, Fiodor Zherebtsov, Viktor F. Mus, et al. Lymphocyte Reproductive Activity Normalized to Numbers of Hematopoietic Stem Cells in Blood and Rate of Death in Fatal Diseases. Int J Genet Genomics. 2017;5(5):54-62. doi: 10.11648/j.ijgg.20170505.12

    Copy | Download

  • @article{10.11648/j.ijgg.20170505.12,
      author = {Aleksei N. Shoutko and Olga A. Gerasimova and Ludmila P. Ekimova and Fiodor Zherebtsov and Viktor F. Mus and Kirill S. Matyurin and Anatoly M. Granov},
      title = {Lymphocyte Reproductive Activity Normalized to Numbers of Hematopoietic Stem Cells in Blood and Rate of Death in Fatal Diseases},
      journal = {International Journal of Genetics and Genomics},
      volume = {5},
      number = {5},
      pages = {54-62},
      doi = {10.11648/j.ijgg.20170505.12},
      url = {https://doi.org/10.11648/j.ijgg.20170505.12},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.ijgg.20170505.12},
      abstract = {The numbers of CD133+ and CD31+ lymphocytes and those in the G2-M phases in the total fraction of circulating lymphocytes from patients with fatal liver cirrhosis and advanced lung cancer were investigated by flow cytometry during a long period of conventional treatment with OLT or palliative surgery followed by myelosuppressive chemotherapy. The relationships of specific reproductive activity, sRA (G2-M/CD133+), and the number of committed liver α-fetoprotein-positive (AFP+) cells with the rate of patient deaths, characterized by exponential approximation survival curves for both diseases, were investigated. Subnormal sRA in patients after OLT and excessive sRA in LC patients above a healthy level were associated with higher death rates and lower survival, coinciding with strong immunosuppression caused by anti-rejection and anti-cancer therapies. These findings may be explained by morphogenesis (feeding) activity of circulating lymphocytes targeted toward both normal and malignant tissues rather than in terms of cellular immunity. The sRA changes may be a useful indicator for monitoring the potential for engraftment or tumor growth.},
     year = {2017}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Lymphocyte Reproductive Activity Normalized to Numbers of Hematopoietic Stem Cells in Blood and Rate of Death in Fatal Diseases
    AU  - Aleksei N. Shoutko
    AU  - Olga A. Gerasimova
    AU  - Ludmila P. Ekimova
    AU  - Fiodor Zherebtsov
    AU  - Viktor F. Mus
    AU  - Kirill S. Matyurin
    AU  - Anatoly M. Granov
    Y1  - 2017/10/18
    PY  - 2017
    N1  - https://doi.org/10.11648/j.ijgg.20170505.12
    DO  - 10.11648/j.ijgg.20170505.12
    T2  - International Journal of Genetics and Genomics
    JF  - International Journal of Genetics and Genomics
    JO  - International Journal of Genetics and Genomics
    SP  - 54
    EP  - 62
    PB  - Science Publishing Group
    SN  - 2376-7359
    UR  - https://doi.org/10.11648/j.ijgg.20170505.12
    AB  - The numbers of CD133+ and CD31+ lymphocytes and those in the G2-M phases in the total fraction of circulating lymphocytes from patients with fatal liver cirrhosis and advanced lung cancer were investigated by flow cytometry during a long period of conventional treatment with OLT or palliative surgery followed by myelosuppressive chemotherapy. The relationships of specific reproductive activity, sRA (G2-M/CD133+), and the number of committed liver α-fetoprotein-positive (AFP+) cells with the rate of patient deaths, characterized by exponential approximation survival curves for both diseases, were investigated. Subnormal sRA in patients after OLT and excessive sRA in LC patients above a healthy level were associated with higher death rates and lower survival, coinciding with strong immunosuppression caused by anti-rejection and anti-cancer therapies. These findings may be explained by morphogenesis (feeding) activity of circulating lymphocytes targeted toward both normal and malignant tissues rather than in terms of cellular immunity. The sRA changes may be a useful indicator for monitoring the potential for engraftment or tumor growth.
    VL  - 5
    IS  - 5
    ER  - 

    Copy | Download

  • Sections