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Endothelial Cells of a Normal Liver and with Hepatocellular Carcinoma

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Abstract—

The article presents a systematic review of the literature data on the role of endothelial cells and features of vascularization in the development of hepatocellular carcinoma. The capillaries of the normal liver are represented by sinusoids, which are characterized by the presence of specific fenestrations in endothelial cells and the absence of a basal membrane under the endothelium. The article shows that, as a rule, the development of hepatocellular carcinoma occurs upon chronic liver lesions, and it is a multistage process of the progression of tissue and cellular atypism, as well as changes in the vascularization of tumor tissue. The vascular network that forms in the tumor tissue is characterized by structural and functional atypism. The development and progression of liver carcinoma is accompanied by changes in the structure and metabolism of endothelial cells in the tumor node, as well as chromosomal aberrations with impaired gene expression and growth factors. The processes of angiogenesis and vascularization are based on the morphological determination of microvessel density on immunohistochemical specimens. The clinical diagnosis of hepatocellular carcinoma is based on the detection of radiation characteristics of the tumor, including those due to changes in vascularization of the tumor tissue. An increase in the malignancy grade of hepatocellular carcinoma is accompanied by a decrease in blood flow through the portal vein system and, accordingly, an increase in arterial blood flow. It is noted that knowledge of the processes of tumor angiogenesis is required to develop antitumor, targeted, antiangiogenic drugs.

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REFERENCES

  1. Aird, W.C., Endothelial cell heterogeneity, Cold Spring Harbor Perspect. Med., 2012, vol. 2, p. a006429.

    Article  Google Scholar 

  2. Akinfiev, D.M., Bakhmutova, E.E., Belyakov, G.A., et al., Luchevaya diagnostika i maloinvazivnoe lechenie mekhanicheskoi zheltukhi (Radiation Diagnostics and Less Invasive Treatment of Obstructive Jaundice), Moscow: Radiologiya-Press, 2010.

  3. Arias, I.M., Alter, H.J., Boyer, J.L., et al., The Liver: Biology and Pathobiology, Chichester: Wiley-Blackwell, 2009.

    Book  Google Scholar 

  4. Ayuso, C., Rimola, J., and García-Criado, A., Imaging of HCC, Abdom. Imaging, 2012, vol. 37, pp. 215–230.

    Article  PubMed  Google Scholar 

  5. Baluk, P., Hashizume, H., and McDonald, D.M., Cellular abnormalities of blood vessels as targets in cancer, Curr. Opin. Genet. Dev., 2005, vol. 15, pp. 102–111.

    Article  CAS  PubMed  Google Scholar 

  6. Braet, F. and Wisse, E., Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: a review, Comp. Hepatol., 2002, vol. 1, p. 1.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bruix, J. and Sherman, M., Management of hepatocellular carcinoma, Hepatology, 2005, vol. 42, pp. 1208–1236.

    Article  PubMed  Google Scholar 

  8. Bussolati, B., Deambrosis, I., Russo, S., et al., Altered angiogenesis and survival in human tumor-derived endothelial cells, FASEB J., 2003, vol. 17, pp. 1159–1161.

    Article  CAS  PubMed  Google Scholar 

  9. Chekmareva, I.A., Vtyurin, B.V., Dubova, E.A., and Shchegolev, A.I., Ultrastructural characteristics of hepatocellular carcinoma, Arkh. Patol., 2010, no. 3, pp. 7–12.

  10. Chen, W.X., Min, P.Q., Song, B., et al., Single-level dynamic spiral CT of hepatocellular carcinoma: correlation between imaging features and density of tumor microvessels, World J. Gastroenterol., 2004, vol. 10, pp. 67–72.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cheng, S.Y., Nagane, M., Huang, H.S., and Cavenee, W.K., Intracerebral tumor-associated hemorrhage caused by overexpression of the vascular endothelial growth factor isoforms VEGF121 and VEGF165 but not VEGF189, Proc. Natl. Acad. Sci. U.S.A., 1997, vol. 94, pp. 12081–12087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cogger, V.C., McNerney, G.P., Nyunt, T., et al., Three-dimensional structured illumination microscopy of liver sinusoidal endothelial cell fenestrations, J. Struct. Biol., 2010, vol. 171, pp. 382–388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Coussens, L.M. and Werb, Z., Inflammation and cancer, Nature, 2002, vol. 420, pp. 860–867.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Daldrup, H., Shames, D.M., Wendland, M., et al., Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media, Am. J. Roentgenol., 1998, vol. 171, pp. 941–949.

    Article  CAS  Google Scholar 

  15. Dan, V.N., Shchegolev, A.I., and Sapelkin, S.V., Modern classifications of congenital vascular malformations (angiodysplasias), Angiol. Sosudistaya Khir., 2006, no. 4, pp. 28–33.

  16. Davies, P.F., Flow-mediated endothelial mechanotransduction, Physiol. Rev., 1995, vol. 75, pp. 519–560.

    Article  CAS  PubMed  Google Scholar 

  17. Davies, P.F., Civelek, M., Fang, Y., and Fleming, I., The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo, Cardiovasc. Res., 2013, vol. 99, pp. 315–327.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. De Bock, K., Georgiadou, M., Schoors, S., et al., Role of PFKFB3-driven glycolysis in vessel sprouting, Cell, 2013, vol. 154, pp. 651–663.

    Article  CAS  PubMed  Google Scholar 

  19. DeLeve, L.D., Liver sinusoidal endothelial cells and liver regeneration, J. Clin. Invest., 2013, vol. 123, pp. 1861–1866.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fan, P.-L., Xia, H.-S., Ding, H., et al., Characterization of early hepatocellular carcinoma and high-grade dysplastic nodules on contrast-enhanced ultrasound: correlation with histopathologic findings, J. Ultrasound Med., 2020, vol. 39, no. 9, pp. 1799–1808. https://doi.org/10.1002/jum.15288

    Article  PubMed  Google Scholar 

  21. Fernandez, M., Molecular pathophysiology of portal hypertension, Hepatology, 2015, vol. 61, pp. 1406–1415.

    Article  PubMed  Google Scholar 

  22. Frachon, S., Gouysse, G., Dumortier, J., et al., Endothelial cell marker expression in dysplastic lesions of the liver: an immunohistochemical study, J. Hepatol., 2001, vol. 34, pp. 850–857.

    Article  CAS  PubMed  Google Scholar 

  23. Franses, J.W., Baker, A.B., Chitalia, V.C., and Edelman, E.R., Stromal endothelial cells directly influence cancer progression, Sci. Transl. Med., 2011, vol. 3, p. 66ra5-5.

    Article  CAS  Google Scholar 

  24. Fraser, R., Cogger, V.C., Dobbs, B., et al., The liver sieve and atherosclerosis, Pathology, 2012, vol. 44, pp. 181–186.

    Article  CAS  PubMed  Google Scholar 

  25. Fukumura, D., Duda, D.G., Munn, L.L., et al., Tumor microvasculature and microenvironment: novel insights through intravital imaging in preclinical models, Microcirculation, 2010, vol. 17, pp. 206–225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Geraud, C., Evdokimov, K., Straub, B.K., et al., Unique cell type-specific junctional complexes in vascular endothelium of human and rat liver sinusoids, PLoS One, 2012, vol. 7, p. e34206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gerhardt, H. and Betsholtz, C., Endothelial-pericyte interactions in angiogenesis, Cell Tissue Res., 2003, vol. 314, pp. 15–23.

    Article  PubMed  Google Scholar 

  28. Gerhardt, H., Golding, M., Fruttiger, M., et al., VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia, J. Cell Biol., 2003, vol. 161, pp. 1163–1177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Geudens, I. and Gerhardt, H., Coordinating cell behaviour during blood vessel formation, Development, 2011, vol. 138, pp. 4569–4583.

    Article  CAS  PubMed  Google Scholar 

  30. Giatromanolaki, A., Sivridis, E., Minopoulos, G., et al., Differential assessment of vascular survival ability and tumor angiogenic activity in colorectal cancer, Clin. Cancer Res., 2002, vol. 8, pp. 1185–1191.

    PubMed  Google Scholar 

  31. Gracia-Sancho, J., Russo, L., García-Calderó, H., et al., Endothelial expression of transcription factor Kruppel-like factor 2 and its vasoprotective target genes in the normal and cirrhotic rat liver, Gut., 2011, vol. 60, pp. 517–524.

    Article  CAS  PubMed  Google Scholar 

  32. Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire, A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma, N. Engl. J. Med., 1995, vol. 332, pp. 1256–1261.

  33. Hanahan, D. and Weinberg, R.A., Hallmarks of cancer: the next generation, Cell, 2011, vol. 144, pp. 646–674.

    Article  CAS  PubMed  Google Scholar 

  34. Haratake, J. and Scheuer, P.J., An immunohistochemical and ultrastructural study of the sinusoids of hepatocellular carcinoma, Cancer, 1990, vol. 65, pp. 1985–1993.

    Article  CAS  PubMed  Google Scholar 

  35. Harb, R., Xie, G., Lutzko, C., et al., Bone marrow progenitor cells repair rat hepatic sinusoidal endothelial cells after liver injury, Gastroenterology., 2009, vol. 137, pp. 704–712.

    Article  PubMed  Google Scholar 

  36. Hendrikx, S., Coso, S., Prat-Luri, B., et al., Endothelial calcineurin signaling restrains metastatic outgrowth by regulating Bmp2, Cell Rep., 2019, vol. 26, pp. 1227–1241.

    Article  CAS  PubMed  Google Scholar 

  37. Hida, K., Hida, Y., Amin, D.N., et al., Tumor-associated endothelial cells with cytogenic abnormalities, Cancer Res., 2004, vol. 64, pp. 8249–8255.

    Article  CAS  PubMed  Google Scholar 

  38. Hida, K., Maishi, N., Kawamoto, T., et al., Tumor endothelial cells express high pentraxin 3 levels, Pathol. Int., 2016, vol. 66, pp. 687–694.

    Article  CAS  PubMed  Google Scholar 

  39. Hida, K., Maishi, N., Akiyama, K., et al., Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance, Cancer Sci., 2017, vol. 108, pp. 2195–2203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Huang, J., Frischer, J.S., Serur, A., et al., Regression of established tumors and metastases by potent vascular endothelial growth factor blockade, Proc. Natl. Acad. Sci. U.S.A., 2003, vol. 100, pp. 7785–7790.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hytiroglou, P., Park, Y.N., Krinsky, G., and Theise, N.D., Hepatic precancerous lesions and small hepatocellular carcinoma, Gastroenterol. Clin. North Am., 2007, vol. 36, pp. 867–887.

    Article  PubMed  Google Scholar 

  42. Isenberg, J.S., Martin-Manso, G., Maxhimer, J.B., et al., Regulation of nitric oxide signaling by thrombospondin-1: implications for anti-angiogenic therapies, Nat. Rev. Cancer, 2009, vol. 9, pp. 182–194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Jeon, H.M., Kim, S.H., Jin, X., et al., Crosstalk between glioma-initiating cells and endothelial cells drives tumor progression, Cancer Res., 2014, vol. 74, pp. 4482–4492.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Jiang, J., Tang, Y.L., and Liang, X.H., EMT: a new vision of hypoxia promoting cancer progression, Cancer Biol. Ther., 2011, vol. 11, pp. 714–723.

    Article  CAS  PubMed  Google Scholar 

  45. Kim, E.S., Serur, A., Huang, J., et al., Potent VEGF blockade causes regression of coopted vessels in a model of neuroblastoma, Proc. Natl. Acad. Sci. U.S.A., 2002, vol. 99, pp. 11399–11404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kim, T.K., Lee, K.H., Jang, H.J., et al., Analysis of gadobenate dimeglumine-enhanced MR findings for characterizing small (1–2-cm) hepatic nodules in patients at high risk for hepatocellular carcinoma, Radiology, 2011, vol. 259, pp. 730–738.

    Article  PubMed  Google Scholar 

  47. Kolios, G., Valatas, V., and Kouroumalis, E., Role of Kupffer cells in the pathogenesis of liver disease, World J. Gastroenterol., 2006, vol. 12, pp. 7413–7420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Le Couteur, D.G., Cogger, V.C., Markus, A.M., et al., Pseudocapillarization and associated energy limitation in the aged rat liver, Hepatology, 2001, vol. 33, pp. 537–543.

    Article  CAS  PubMed  Google Scholar 

  49. Lee, S.S., Hadengue, A., Moreau, R., et al., Postprandial hemodynamic responses in patients with cirrhosis, Hepatology, 1988, vol. 8, pp. 647–651.

    Article  CAS  PubMed  Google Scholar 

  50. Llovet, J.M., Ricci, S., Mazzaferro, V., et al., Sorafenib in advanced hepatocellular carcinoma, N. Engl. J. Med., 2008, vol. 359, pp. 378–390.

    Article  CAS  PubMed  Google Scholar 

  51. London, W.T., Liver cancer, in Cancer Epidemiology and Prevention, Schottenfeld, D. and Fraumeni, J., Jr., Eds., 3rd ed., Oxford: Oxford Univ. Press, 2006, pp. 763–786.

    Google Scholar 

  52. Magnussen, A., Kasman, I.M., Norberg, S., et al., Rapid access of antibodies to α5β1 integrin overexpressed on the luminal surface of tumor blood vessels, Cancer Res., 2005, vol. 65, pp. 2712–2721.

    Article  CAS  PubMed  Google Scholar 

  53. Maishi, N., Ohba, Y., Akiyama, K., et al., Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan, Sci. Rep., 2016, vol. 6, p. 28039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Marcu, R., Choi, Y.J., Xue, J., et al., Human organ-specific endothelial cell heterogeneity, Science, 2018, vol. 4, pp. 20–35.

    CAS  Google Scholar 

  55. Margreet De Leeuw, A., Brouwer, A., and Knook, D.L., Sinusoidal endothelial cells of the liver: fine structure and function in relation to age, J. Electron. Microsc. Tech., 1990, vol. 14, pp. 218–236.

    Article  Google Scholar 

  56. Marien, K.M., Croons, V., Waumans, Y., et al., Development and validation of a histological method to measure microvessel density in whole-slide images of cancer tissue, PLoS One, 2016, vol. 11, p. e0161496.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Marrero, J.A., Hussain, H.K., Nghiem, H.V., et al., Improving the prediction of hepatocellular carcinoma in cirrhotic patients with an arterially-enhancing liver mass, Liver Transpl., 2005, vol. 11, pp. 281–289.

    Article  PubMed  Google Scholar 

  58. Matsuda, K., Ohga, N., Hida, Y., et al., Isolated tumor endothelial cells maintain specific character during long-term culture, Biochem. Biophys. Res. Commun., 2010, vol. 394, pp. 947–954.

    Article  CAS  PubMed  Google Scholar 

  59. Maxwell, P.H., Dachs, G.U., Gleadle, J.M., et al., Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth, Proc. Natl. Acad. Sci. U.S.A., 1997, vol. 94, pp. 8104–8109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Mazzaferro, V., Lencioni, R., and Majno, P., Early hepatocellular carcinoma on the procrustean bed of ablation, resection, and transplantation, Semin. Liver Dis., 2014, vol. 34, pp. 415–426.

    Article  PubMed  Google Scholar 

  61. Mazzone, M., Dettori, D., de Oliveira, R.L., et al., Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization, Cell, 2009, vol. 136, pp. 839–851.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. McDonald, D.M. and Choyke, P.L., Imaging of angiogenesis: from microscope to clinic, Nat. Med., 2003, vol. 9, pp. 713–725.

    Article  CAS  PubMed  Google Scholar 

  63. McLean, A.J., Cogger, V.C., Chong, G.C., et al., Age-related pseudocapillarization of the human liver, J. Pathol., 2003, vol. 200, pp. 112–117.

    Article  PubMed  Google Scholar 

  64. Mönkemöller, V., Øie, C., Hübner, W., et al., Multimodal superresolution optical microscopy visualizes the close connection between membrane and the cytoskeleton in liver sinusoidal endothelial cell fenestrations, Sci. Rep., 2015, vol. 5, p. 16279.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. O’Reilly, J.N., Cogger, V.C., Fraser, R., and Le Couteur, D.G., The effect of feeding and fasting on fenestrations in the liver sinusoidal endothelial cell, Pathology (Philadelphia), 2010, vol. 42, pp. 255–258.

    Article  PubMed  Google Scholar 

  66. Ohga, N., Ishikawa, S., Maishi, N., et al., Heterogeneity of tumor endothelial cells: comparison between tumor endothelial cells isolated from high- and low-metastatic tumors, Am. J. Pathol., 2012, vol. 180, pp. 1294–1307.

    Article  CAS  PubMed  Google Scholar 

  67. Ohmura-Kakutani, H., Akiyama, K., Maishi, N., et al., Identification of tumor endothelial cells with high aldehyde dehydrogenase activity and a highly angiogenic phenotype, PLoS One, 2014, vol. 9, p. e113910.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Otsubo, T., Hida, Y., Ohga, N., et al., Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells, Cancer. Sci., 2014, vol. 105, pp. 560–567.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Pang, R. and Poon, R.T., Angiogenesis and antiangiogenic therapy in hepatocellular carcinoma, Cancer Lett., 2006, vol. 242, pp. 151–167.

    Article  CAS  PubMed  Google Scholar 

  70. Park, Y.N. and Kim, M.-J., Hepatocarcinogenesis: imaging-pathologic correlation, Abdom. Imaging, 2011, vol. 36, pp. 232–243.

    Article  PubMed  Google Scholar 

  71. Park, Y.N., Kim, Y.B., Yang, K.M., and Park, C., Increased expression of vascular endothelial growth factor and angiogenesis in the early stage of multistep hepatocarcinogenesis, Arch. Pathol. Lab. Med., 2000, vol. 124, pp. 1061–1065.

    Article  CAS  PubMed  Google Scholar 

  72. Parmar, K.M., Larman, H.B., Dai, G., et al., Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2, J. Clin. Invest., 2006, vol. 116, pp. 49–58.

    Article  CAS  PubMed  Google Scholar 

  73. Perrot, C.Y., Javelaud, D., and Mauviel, A., Insights into the transforming growth factor-β signaling pathway in cutaneous melanoma, Ann. Dermatol., 2013, vol. 25, pp. 135–144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ping, Y.F. and Bian, X.W., Concise review: contribution of cancer stem cells to neovascularization, Stem Cells, 2011, vol. 29, pp. 888–894

    Article  CAS  PubMed  Google Scholar 

  75. Pirtskhalaishvili, G. and Nelson, J.B., Endothelium-derived factors as paracrine mediators of prostate cancer progression, Prostate, 2000, vol. 44, pp. 77–87.

    Article  CAS  PubMed  Google Scholar 

  76. Poon, R.T., Ng, I.O., Lau, C., et al., Tumor microvessel density as a predictor of recurrence after resection of hepatocellular carcinoma: a prospective study, J. Clin. Oncol., 2002, vol. 20, pp. 1775–1785.

    Article  PubMed  Google Scholar 

  77. Poon, R., Ho, J., Tong, C., et al., Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma, Br. J. Surg., 2004, vol. 91, pp. 1354–1360.

    Article  CAS  PubMed  Google Scholar 

  78. Raskopf, E., Vogt, A., Sauerbruch, T., and Schmitz, V., siRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo, J. Hepatol., 2008, vol. 49, pp. 977–984.

    Article  CAS  PubMed  Google Scholar 

  79. Ria, R., Todoerti, K., Berardi, S., et al., Gene expression profiling of bone marrow endothelial cells in patients with multiple myeloma, Clin. Cancer Res., 2009, vol. 15, pp. 5369–5378.

    Article  CAS  PubMed  Google Scholar 

  80. Ribatti, D., The crucial role of vascular permeability factor/vascular endothelial growth factor in angiogenesis: a historical review, Br. J. Haematol., 2005, vol. 128, pp. 303–309.

    Article  CAS  PubMed  Google Scholar 

  81. Roncalli, M., Roz, E., Coggi, G., et al., The vascular profile of regenerative and dysplastic nodules of the cirrhotic liver: implications for diagnosis and classification, Hepatology, 1999, vol. 30, pp. 1174–1178.

    Article  CAS  PubMed  Google Scholar 

  82. Sabbagh, M.F., Heng, J.S., Luo, C., et al., Transcriptional and epigenomic landscapes of CNS and non-CNS vascular endothelial cells, eLife, 2018, vol. 7, p. e36187.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Sakamoto, M., Early HCC: diagnosis and molecular markers, J. Gastroenterol., 2009, vol. 44, pp. 108–111.

    Article  CAS  PubMed  Google Scholar 

  84. Sato, T., Kondo, F., Ebara, M., et al., Natural history of large regenerative nodules and dysplastic nodules in liver cirrhosis: 28-year follow-up study, Hepatol. Int., 2015, vol. 9, pp. 330–336.

    Article  PubMed  Google Scholar 

  85. Seale, M.K., Catalano, O.A., Saini, S., et al., Hepatobiliary-specific MR contrast agents: role in imaging the liver and biliary tree, Radiographics, 2009, vol. 29, pp. 1725–1748.

    Article  PubMed  Google Scholar 

  86. Semela, D. and Dufour, J.-F., Angiogenesis and hepatocellular carcinoma, J. Hepatol., 2004, vol. 41, pp. 864–880.

    Article  PubMed  Google Scholar 

  87. Shah, V., Haddad, F.G., Garcia-Cardena, G., et al., Liver sinusoidal endothelial cells are responsible for nitric oxide modulation of resistance in the hepatic sinusoids, J. Clin. Invest., 1997, vol. 100, pp. 2923–2930.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Shchegolev, A.I., and Mishnev, O.D., Structural and metabolic characteristics of sinusoidal liver cells, Usp. Sovrem. Biol., 1991, vol. 111, no. 1, pp. 73–82.

    CAS  Google Scholar 

  89. Shchegolev, A.I., and Mishnev, O.D., Onkomorfologiya pecheni (Oncomorphology of the Liver), Moscow: Ross. Gos. Med. Univ., 2006.

  90. Shchegolev, A.I., Tumanova, U.N., and Mishnev, O.D., Classification and morphological characteristics of hepatocellular nodular liver lesions, Mezhdunar. Zh. Prikl. Fundam. Issled., 2017, no. 1-1, pp. 71–75.

  91. Shchyogolev, A.I., Dubova, E.A., and Tumanova, U.N., Vascularization of hepatocellular carcinoma tissue depends on its differentiation degree, Bull. Exp. Biol. Med., 2012, vol. 153, pp. 490–494.

    Article  CAS  PubMed  Google Scholar 

  92. Soda, Y., Marumoto, T., Friedmann-Morvinski, D., et al., Transdifferentiation of glioblastoma cells into vascular endothelial cells, Proc. Natl. Acad. Sci. U.S.A., 2011, vol. 108, pp. 4274–4280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Sostoyanie onkologicheskoi pomoshchi naseleniyu Rossii v 2018 godu (Oncological Care Service for the Population of Russia in 2018), Kaprin, A.D., Starinskii, V.V., and Petrova, G.V., Eds., Moscow: Mosk. Nauchno-Issled. Onkol. Inst. im. P.A. Gertsena, 2019.

  94. St. Croix, B., Rago, C., Velculescu, V., et al., Gene expressed in human tumor and endothelium, Science, 2000, vol. 289, pp. 1197–1202.

    Article  CAS  PubMed  Google Scholar 

  95. Suh, Y., Yoon, C.H., Kim, R.K., et al., Claudin-1 induces epithelial-mesenchymal transition through activation of the c-Abl-ERK signaling pathway in human liver cells, Oncogene, 2013, vol. 32, pp. 4873–4882.

    Article  CAS  PubMed  Google Scholar 

  96. Sun, B., Zhang, S., Zhang, D., et al., Vasculogenic mimicry is associated with high tumor grade, invasion and metastasis, and short survival in patients with hepatocellular carcinoma, Oncol. Rep., 2006, vol. 16, pp. 693–698.

    CAS  PubMed  Google Scholar 

  97. Tong, R.T., Boucher, Y., Kozin, S.V., et al., Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors, Cancer Res., 2004, vol. 64, pp. 3731–3736.

    Article  CAS  PubMed  Google Scholar 

  98. Torre, L.A., Bray, F., Siegel, R.L., et al., Global cancer statistics, 2012, Ca-Cancer J. Clin., 2011, vol. 65, pp. 87–108.

    Article  Google Scholar 

  99. Tumanova, U.N. and Shchegolev, A.I., Vascularization of hepatocellular carcinoma, Arkh. Patol., 2015a, vol. 77, no. 2, pp. 50–55.

    Article  CAS  PubMed  Google Scholar 

  100. Tumanova, U.N. and Shchegolev, A.I., Angiogenesis in hepatocellular carcinoma, Biol. Bull. Rev., 2015b, vol. 5, no. 6, pp. 568–578.

    Article  Google Scholar 

  101. Tumanova, U.N., Dubova, E.A., Karmazanovskii, G.G., and Shchegolev, A.I., Computed tomographic and morphological comparisons in hepatocellular carcinoma at various grades of differentiation, Mol. Med., 2012a, no. 5, pp. 35–40.

  102. Tumanova, U.N., Karmazanovskii, G.G., and Shchegolev, A.I., Densitometric characteristics of hepatocellular carcinoma at spiral computed tomography, Med. Vizualizatsiya, 2012b, no. 6, pp. 42–49.

  103. Tumanova, U.N., Dubova, E.A., Karmazanovskii, G.G., and Shchegolev, A.I., CT characteristics of the vasculature and blood supply of hepatocellullar carcinoma, Ann. Khir. Gepatol., 2013a, vol. 18, no. 4, pp. 53–60.

    Google Scholar 

  104. Tumanova, U.N., Karmazanovskii, G.G., Dubova, E.A., and Shchegolev, A.I., Comparative analysis of vascularization degree of hepatocellular carcinoma and focal nodular hyperplasia of the liver according to computed tomography and morphological studies, Vestn. Ross. Akad. Med. Nauk, 2013b, vol. 68, no. 12, pp. 9–15.

    Article  Google Scholar 

  105. Tumanova, U.N., Karmazanovskii, G.G., and Shchegolev, A.I., Characterisatics of the degree of vascularization of hepatocellular carcinoma determined by spiral computed tomography, Med. Vizualizatsiya, 2013c, no. 1, pp. 52–58.

  106. Tumanova, U.N., Karmazanovskii, G.G., and Shchegolev, A.I., LI-RADS system for computer-tomographic diagnosis of hepatocellular carcinoma, Med. Vizualizatsiya, 2014, no. 6, pp. 44–50.

  107. Tumanova, U.N., Karmazanovskii, G.G., Yashina, N.I., and Shchegolev, A.I., Diagnostic significance of computer-tomographic characteristics of hepatocellular carcinoma nodes depending on size, Ross. Elektron. Zh. Luchevoi Diagn., 2016, vol. 6, no. 4, pp. 44–55.

    Google Scholar 

  108. Ueki, T., Sakaguchi, S., Miyajima, Y., et al., Usefulness of tumor pressure as a prognostic factor in cases of hepatocellular carcinoma where the diameter of the tumor is 3 cm or less, Cancer, 2002, vol. 95, pp. 596–604.

    Article  PubMed  Google Scholar 

  109. Vascular Liver Disease: Mechanisms and Management, DeLeve, L.D. and Garcia-Tsao, G., Eds., New York: Springer-Verlag, 2011.

  110. Vasuri, F., Fittipaldi, S., Giunchi, F., et al., Facing the enigma of the vascular network in hepatocellular carcinomas in cirrhotic and non-cirrhotic livers, J. Clin. Pathol., 2016, vol. 69, pp. 102–108.

    Article  CAS  PubMed  Google Scholar 

  111. Vermeulen, P.B., Verhoeven, D., Hubens, G., et al., Microvessels density, endothelial cell proliferation and tumor cell proliferation in human colorectal adenocarcinomas, Ann. Oncol., 1995, vol. 6, pp. 59–64.

    Article  CAS  PubMed  Google Scholar 

  112. Vidal-Vanaclocha, F. and Barbera-Guillem, E., Fenestration patterns in endothelial cells of rat liver sinusoids, J. Ultrastruct. Res., 1985, vol. 90, pp. 115–123.

    Article  CAS  PubMed  Google Scholar 

  113. Wang, L., Wang, X., Xie, G., et al., Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats, J. Clin. Invest., 2012, vol. 122, pp. 1567–1573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Warren, A., Chaberek, S., Ostrowski, K., et al., Effects of old age on vascular complexity and dispersion of the hepatic sinusoidal network, Microcirculation, 2008, vol. 15, pp. 191–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Weidner, N., Semple, J.P., Welch, W.R., and Folkman, J., Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma, N. Engl. J. Med., 1991, vol. 324, pp. 1–8.

    Article  CAS  PubMed  Google Scholar 

  116. Wicki, A. and Christofori, G., The angiogenic switch in tumorigenesis, in Tumor Angiogenesis: Basic Mechanisms and Cancer Therapy, Marmé, D. and Fusenig, N., Eds., Berlin: Springer-Verlag, 2008, pp. 67–88.

    Google Scholar 

  117. Wieland, E., Rodriguez-Vita, J., Liebler, S.S., et al., Endothelial Notch1 activity facilitates metastasis, Cancer Cell, 2017, vol. 31, pp. 355–367.

    Article  CAS  PubMed  Google Scholar 

  118. Wisse, E., Braet, F., Duimel, H., et al., Fixation methods for electron microscopy of human and other liver, World J. Gastroenterol., 2020, vol. 21, pp. 2851–2866.

    Google Scholar 

  119. Xiong, Y.Q., Sun, H.C., Zhang, W., et al., Human hepatocellular carcinoma tumor-derived endothelial cells manifest increased angiogenesis capability and drug resistance compared with normal endothelial cells, Clin. Cancer Res., 2009, vol. 15, pp. 4838–4846.

    Article  CAS  PubMed  Google Scholar 

  120. Zhu, A.X., Duda, D.G., Sahani, D.V., and Jain, R.K., HCC and angiogenesis: possible targets and future directions, Nat. Rev. Clin. Oncol., 2011, vol. 8, pp. 292–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Healthcare of Russian Federation, Moscow, Russia

    A. I. Shchegolev & U. N. Tumanova

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  1. A. I. Shchegolev
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  2. U. N. Tumanova
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Shchegolev, A.I., Tumanova, U.N. Endothelial Cells of a Normal Liver and with Hepatocellular Carcinoma. Biol Bull Rev 11, 172–185 (2021). https://doi.org/10.1134/S2079086421020092

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