Estudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástrico

ilustraciones, fotografías a color

Autores:
Sossa Rojas, Henry
Tipo de recurso:
Doctoral thesis
Fecha de publicación:
2022
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/83759
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/83759
https://repositorio.unal.edu.co
Palabra clave:
610 - Medicina y salud::615 - Farmacología y terapéutica
610 - Medicina y salud::611 - Anatomía humana, citología, histología
610 - Medicina y salud::616 - Enfermedades
Neoplasias gástricas
Gastrectomía
Stomach Neoplasms
Gastrectomy
Rotavirus
Terapia viral oncolítica
Cáncer gástrico
Apoptosis
Lisis tumoral
Rotavirus
Oncolytic viral therapy
Gastric cancer
Apoptosis
Tumor lysis
Rights
openAccess
License
Reconocimiento 4.0 Internacional
id UNACIONAL2_b4c3a93715356b68f38b508fb3e377f0
oai_identifier_str oai:repositorio.unal.edu.co:unal/83759
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Estudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástrico
dc.title.translated.eng.fl_str_mv Oncolytic potential of human rotaviral isolation Wt 1-5 in gastric adenocarcinoma
title Estudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástrico
spellingShingle Estudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástrico
610 - Medicina y salud::615 - Farmacología y terapéutica
610 - Medicina y salud::611 - Anatomía humana, citología, histología
610 - Medicina y salud::616 - Enfermedades
Neoplasias gástricas
Gastrectomía
Stomach Neoplasms
Gastrectomy
Rotavirus
Terapia viral oncolítica
Cáncer gástrico
Apoptosis
Lisis tumoral
Rotavirus
Oncolytic viral therapy
Gastric cancer
Apoptosis
Tumor lysis
title_short Estudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástrico
title_full Estudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástrico
title_fullStr Estudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástrico
title_full_unstemmed Estudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástrico
title_sort Estudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástrico
dc.creator.fl_str_mv Sossa Rojas, Henry
dc.contributor.advisor.none.fl_str_mv Guerrero Fonseca, Carlos Arturo
dc.contributor.author.none.fl_str_mv Sossa Rojas, Henry
dc.contributor.researchgroup.spa.fl_str_mv Biología Celular
Biología Molecular de Virus
Biotecnología Microbiana
dc.contributor.orcid.spa.fl_str_mv 0000-0001-7854-0689
dc.subject.ddc.spa.fl_str_mv 610 - Medicina y salud::615 - Farmacología y terapéutica
610 - Medicina y salud::611 - Anatomía humana, citología, histología
610 - Medicina y salud::616 - Enfermedades
topic 610 - Medicina y salud::615 - Farmacología y terapéutica
610 - Medicina y salud::611 - Anatomía humana, citología, histología
610 - Medicina y salud::616 - Enfermedades
Neoplasias gástricas
Gastrectomía
Stomach Neoplasms
Gastrectomy
Rotavirus
Terapia viral oncolítica
Cáncer gástrico
Apoptosis
Lisis tumoral
Rotavirus
Oncolytic viral therapy
Gastric cancer
Apoptosis
Tumor lysis
dc.subject.decs.spa.fl_str_mv Neoplasias gástricas
Gastrectomía
dc.subject.decs.eng.fl_str_mv Stomach Neoplasms
Gastrectomy
dc.subject.proposal.spa.fl_str_mv Rotavirus
Terapia viral oncolítica
Cáncer gástrico
Apoptosis
Lisis tumoral
dc.subject.proposal.eng.fl_str_mv Rotavirus
Oncolytic viral therapy
Gastric cancer
Apoptosis
Tumor lysis
description ilustraciones, fotografías a color
publishDate 2022
dc.date.issued.none.fl_str_mv 2022-07-01
dc.date.accessioned.none.fl_str_mv 2023-04-24T13:40:56Z
dc.date.available.none.fl_str_mv 2023-04-24T13:40:56Z
dc.type.spa.fl_str_mv Trabajo de grado - Doctorado
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/doctoralThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_db06
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TD
format http://purl.org/coar/resource_type/c_db06
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/83759
dc.identifier.instname.spa.fl_str_mv Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv https://repositorio.unal.edu.co
url https://repositorio.unal.edu.co/handle/unal/83759
https://repositorio.unal.edu.co
identifier_str_mv Universidad Nacional de Colombia
Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv spa
language spa
dc.relation.references.spa.fl_str_mv Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49.
International Agency for Research on Cancer. CANCER TODAY [Internet]. World Health Organization. [cited 2020 Dec 16]. Available from: https://gco.iarc.fr/today/home
Pardo C, Vries EDE, Buitrago L, Gamboa O. Atlas de mortalidad por cáncer en Colombia. 4th ed. Cancerologia IN de, editor. Bogota: Instituto Nacional de Cancerologia; 2017. 124 p.
Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21(5):449–56.
Naghavi M, Wang H, Lozano R, Davis A, Liang X, Zhou M, et al. Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385(9963):117–71.
DIgklia A, Wagner AD. Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroenterol. 2016;22(8):2403–14.
Guo Q, Jing FJ, Qu HJ, Xu W, Han B, Xing XM, et al. Ubenimex Reverses MDR in Gastric Cancer Cells by Activating Caspase-3-Mediated Apoptosis and Suppressing the Expression of Membrane Transport Proteins. Biomed Res Int. 2019;2019.
Smyth EC, Moehler M. Late-line treatment in metastatic gastric cancer: today and tomorrow. Ther Adv Med Oncol. 2019;11:1–11.
Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18(3):197–218.
Russell SJ, Peng KW. Viruses as anticancer drugs. Trends Pharmacol Sci. 2007;28(7):326–33.
Lowy D. NCI Dictionary of Cancer Terms - National Cancer Institute [Internet]. National Cancer Institute - at the National Institiutes of Health. [cited 2015 Nov 4]. Available from: http://www.cancer.gov/dictionary?cdrid=46216
Chiocca EA, Rabkin SD. Oncolytic Viruses and Their Application to Cancer Immunotherapy. Cancer Immunol Res. 2014;2(4):295–300.
Zhou J, Wang G, Chen Y, Wang H, Hua Y, Cai Z. Immunogenic cell death in cancer therapy: Present and emerging inducers. J Cell Mol Med. 2019;23(8):4854–65.
Guo ZS, Liu Z, Kowalsky S, Feist M, Kalinski P, Lu B, et al. Oncolytic immunotherapy: Conceptual evolution, current strategies, and future perspectives. Front Immunol. 2017;8(555):1–15.
Bommareddy PK, Shettigar M, Kaufman HL. Integrating oncolytic viruses in combination cancer immunotherapy. Nat Rev Immunol. 2018;18(August):1–16.
International Committee on Taxonomy of Viruses (ICTV) [Internet]. [cited 2020 Oct 24]. Available from: https://talk.ictvonline.org/taxonomy/
Matthijnssens J, Otto PH, Ciarlet M, Desselberger U, van Ranst M, Johne R. VP6-sequence-based cutoff values as a criterion for rotavirus species demarcation. Arch Virol. 2012;157(6):1177–82.
Matthijnssens J, Ciarlet M, Rahman M, Attoui H, Estes MK, Gentsch JR, et al. Recommendations for the classification of group A rotaviruses using all 11 genomic RNA segments. Arch Virol. 2009;153(8):1621–9.
Contreras-Treviño HI, Reyna-Rosas E, León-Rodríguez R, Ruiz-Ordaz BH, Dinkova TD, Cevallos AM, et al. Species A rotavirus NSP3 acquires its translation inhibitory function prior to stable dimer formation. PLoS One. 2017;12(7):1–18.
Esona MD, Gautam R. Rotavirus. Clin Lab Med. 2015;35(2):363–91.
Rojas M, Ayala-Breton C, Lopez S. BIOLOGÍA MOLECULAR DE ROTAVIRUS : UNA MIRADA A TRAVÉS DE LA INTERFERENCIA DE RNA. MENSAJE BIOQUÍMICO. 2008;XXXII:149–62.
Matthijnssens J, Ciarlet M, McDonald SM, Attoui H, Bányai K, Brister JR, et al. Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG). Arch Virol. 2011;156(8):1397–413.
Morelli M, Ogden KM, Patton JT. Silencing the alarms: Innate immune antagonism by rotavirus NSP1 and VP3. Virology. 2015;479-480C:75–84.
Yu X, Blanchard H. Carbohydrate recognition by rotaviruses. J Struct Funct Genomics. 2014;15(3):101–6.
Giaginis C, Daskalopoulou SS, Vgenopoulou S, Sfiniadakis I, Kouraklis G, Theocharis SE. Heat Shock Protein-27, -60 and -90 expression in gastric cancer: association with clinicopathological variables and patient survival. BMC Gastroenterol. 2009;9(14):1–10.
Sharma PC, Verma R. Implication of HSP70 in the Pathogenesis of Gastric Cancer. In: HSP70 in Human Diseases and Disorders. Springer Nature; 2018. p. 113–30.
Moreira AM, Pereira J, Melo S, Fernandes MS, Carneiro P, Seruca R, et al. The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression. Cells. 2020;9(2):394.
Xu YH, Li ZL, Qiu SF. IFN-γ Induces Gastric Cancer Cell Proliferation and Metastasis Through Upregulation of Integrin β3-Mediated NF-κB Signaling. Transl Oncol. 2018;11(1):182–92.
Wu Z, Zhang L, Li N, Sha L, Zhang K. An immunohistochemical study of thioredoxin domain-containing 5 expression in gastric adenocarcinoma. Oncol Lett. 2015;9(3):1154–8.
Shimoda T, Wada R, Kure S, Ishino K, Kudo M, Ohashi R, et al. Expression of protein disulfide isomerase A3 and its clinicopathological association in gastric cancer. Oncol Rep. 2019;41(4):2265–72.
Guerrero CA, Guerrero RA, Silva E, Acosta O, Barreto E. Experimental Adaptation of Rotaviruses to Tumor Cell Lines. PLoS One. 2016;11(2):1–25
Guerrero C a, Bouyssounade D, Zárate S, Isa P, López T, Espinosa R, et al. Heat Shock Cognate Protein 70 Is Involved in Rotavirus Cell Entry Heat Shock Cognate Protein 70 Is Involved in Rotavirus Cell Entry. J Virol. 2002;76(8):4096–102.
Santana AY, Guerrero CA, Acosta O. Implication of Hsc70, PDI and integrin αvβ3 involvement during entry of the murine rotavirus ECwt into small-intestinal villi of suckling mice. Arch Virol. 2013;158(6):1323–36.
Guerrero RA, Guerrero CA, Guzmán F, Acosta O. Assessing the oncolytic potential of rotavirus on mouse myeloma cell line Sp2/0-Ag14. Biomedica. 2020;40(2).
Laurén P. the Two Histological Main Types of Gastric Carcinoma: Diffuse and So-Called Intestinal-Type Carcinoma. an Attempt At a Histo-Clinical Classification. Acta Pathol Microbiol Scand. 1965;64:31–49.
Pinho SS, Carvalho S, Marcos-Pinto R, Magalhães A, Oliveira C, Gu J, et al. Gastric cancer: Adding glycosylation to the equation. Trends Mol Med. 2013;19(11):664–76.
Kang SH, Kim JS, Moon HS, Lee ES, Kim SH, Sung JK, et al. Signet ring cell carcinoma of early gastric cancer, is endoscopic treatment really risky? Medicine (Baltimore). 2017;96(33):1–5.
Ohtsuka J, Oshima H, Ezawa I, Abe R, Oshima M, Ohki R. Functional loss of p53 cooperates with the in vivo microenvironment to promote malignant progression of gastric cancers. Sci Rep. 2018;8(1):1–15.
Pan X, Ji X, Zhang R, Zhou Z, Zhong Y, Peng W, et al. Landscape of somatic mutations in gastric cancer assessed using next-generation sequencing analysis. Oncol Lett. 2018;16(4):4863–70.
Li W, Luo S, Ma G, Wang L. <p>Impact of liver kinase B1 on p53 and survivin and its correlation with prognosis in gastric cancer</p>. Onco Targets Ther. 2019;Volume 12:1439–45.
Yildirim M, Kaya V, Demirpence O, Gunduz S, Bozcuk H. Prognostic significance of p53 in gastric cancer: A meta-analysis. Asian Pacific J Cancer Prev. 2015;16(1):327–32.
Lee JY, Gong EJ, Chung EJ, Park HW, Bae SE, Kim EH, et al. The characteristics and prognosis of diffuse-type early gastric cancer diagnosed during health check-ups. Gut Liver. 2017;11(6):807–12.
Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison’s Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2). McGraw Hill Higher Education. 2018.
Ma J, Shen H, Kapesa L, Zeng S. Lauren classification and individualized chemotherapyin gastric cancer (Review). Oncol Lett. 2016;11(5):2959–64
Singh SR. Gastric cancer stem cells: a novel therapeutic target. Cancer Lett. 2013 Sep 10;338(1):110–9.
Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev. 2014;23(5):700–13.
Nakamura K, Sugano H, Takagi K. Carcinoma of the stomach in incipient phase: its histogenesis and histological appearances. Gan. 1968;59(3):251–8.
Pernot S, Voron T, Perkins G, Lagorce-Pages C, Berger A, Taieb J. Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge. World J Gastroenterol. 2015;21(40):11428–38.
Lai JF, Xu WN, Noh SH, Lu WQ. Effect of world health organization (WHO) histological classification on predicting lymph node metastasis and recurrence in early gastric cancer. Med Sci Monit. 2016;22:3147–53.
Mahadevan V. Anatomy of the stomach. Surg (United Kingdom). 2017;35(11):608–11.
Nie S, Yuan Y. The Role of Gastric Mucosal Immunity in Gastric Diseases. J Immunol Res. 2020;2020:1–8.
Liu JY, Peng CW, Yang XJ, Huang CQ, Li Y. The prognosis role of AJCC/UICC 8th edition staging system in gastric cancer, a retrospective analysis. Am J Transl Res. 2018;10(1):292–303.
Escrig Sos J, Gómez Quiles L, Maiocchi K. The 8th edition of the AJCC-TNM classification: New contributions to the staging of esophagogastric junction cancer. Cir Esp. 2019;97(8):432–7.
Wang FH, Shen L, Li J, Zhou ZW, Liang H, Zhang XT, et al. The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer. Cancer Commun. 2019;39(1):1–31.
Rodriquenz MG, Roviello G, D’Angelo A, Lavacchi D, Roviello F, Polom K. MSI and EBV Positive Gastric Cancer’s Subgroups and Their Link With Novel Immunotherapy. J Clin Invest. 2020;9(1427):1–12.
Ham IH, Lee D, Hur H. Role of cancer-associated fibroblast in gastric cancer progression and resistance to treatments. J Oncol. 2019;2019:1–11.
Angell HK, Bruni D, Carl Barrett J, Herbst R, Galon J. The immunoscore: Colon cancer and beyond a C. Clin Cancer Res. 2020;26(2):332–9.
Chia NY, Tan P. Molecular classification of gastric cancer. Ann Oncol. 2016;27(5):763–9.
Wang X, Mao M, Zhu S, Xing S, Song Y, Zhang L, et al. A Novel Nomogram Integrated with Inflammation-Based Factors to Predict the Prognosis of Gastric Cancer Patients. Adv Ther. 2020
Link A, Kupcinskas J. MicroRNAs as non-invasive diagnostic biomarkers for gastric cancer: Current insights and future perspectives. World J Gastroenterol. 2018;24(30):3313–29.
Marrelli D, Pinto E, De Stefano A, Farnetani M, Garosi L, Roviello F. Clinical utility of CEA, CA 19-9, and CA 72-4 in the follow-up of patients with resectable gastric cancer. Am J Surg. 2001;181(1):16–9.
You W, Cai Z, Sheng N, Yan L, Wan H, Wang Y, et al. Construction and Validation of Convenient Clinicopathologic Signatures for Predicting the Prognosis of Stage I-III Gastric Cancer. Front Oncol. 2022;12(March):1–9.
Zhou C, Zhong X, Song Y, Shi J, Wu Z, Guo Z, et al. Prognostic Biomarkers for Gastric Cancer: An Umbrella Review of the Evidence. Front Oncol. 2019;9(November):1–16.
Hao NB, He YF, Li XQ, Wang K, Wang RL. The role of miRNA and lncRNA in gastric cancer. Oncotarget. 2017;8(46):81572–82.
Bass AJ, Thorsson V, Shmulevich I, Reynolds SM, Miller M, Bernard B, et al. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9.
Oliveira C, Suriano G, Ferreira P, Canedo P, Kaurah P, Mateus R, et al. Genetic screening for familial gastric cancer. Hered Cancer Clin Pract. 2004;2(2):51–64.
Yao Y, Dai W. Genomic Instability and Cancer. J Carcinog Mutagen. 2014;5:1–17.
Baj J, Brzozowska K, Forma A, Maani A, Sitarz E, Portincasa P. Immunological aspects of the tumor microenvironment and epithelial-mesenchymal transition in gastric carcinogenesis. Int J Mol Sci. 2020;21(7).
Herbert A. ADAR and Immune Silencing in Cancer. Trends in Cancer. 2019;5(5):272–82.
Ignatova E, Seriak D, Fedyanin M, Tryakin A, Pokataev I. Epstein – Barr virus-associated gastric cancer : disease that requires special approach. Gastric Cancer. 2020;(0123456789).
Tsugane S, Sasazuki S. Diet and the risk of gastric cancer: Review of epidemiological evidence. Gastric Cancer. 2007;10(2):75–83.
Rawla P, Barsouk A. Epidemiology of gastric cancer: Global trends, risk factors and prevention. Prz Gastroenterol. 2019;14(1):26–38.
Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, et al. Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 2012;91(3):1071–121.
Giraldo NA, Sanchez-Salas R, Peske JD, Vano Y, Becht E, Petitprez F, et al. The clinical role of the TME in solid cancer. Br J Cancer. 2019;120(1):45–53.
Rezalotfi A, Ahmadian E, Aazami H, Solgi G, Ebrahimi M. Gastric cancer stem cells effect on Th17/Treg balance. A bench to beside perspective. Front Oncol. 2019;9(4):1–13.
Blidner AG, Méndez-Huergo SP, Cagnoni AJ, Rabinovich GA. Re-wiring regulatory cell networks in immunity by galectin-glycan interactions. FEBS Lett. 2015;589(22):3407–18.
Chang CH, Qiu J, O’Sullivan D, Buck MD, Noguchi T, Curtis JD, et al. Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression. Cell. 2015;162(6):1229–41.
Vigneron N. Human Tumor Antigens and Cancer Immunotherapy. Biomed Res Int. 2015;2015:1–17.
Hanahan D, Coussens LM. Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment. Cancer Cell. 2012;21(3):309–22.
Maitra A. Pancreatic cancer hidden in plain sight. Nature. 2020 May 1;581(7806):34–5.
Dudley AC. Tumor endothelial cells. Cold Spring Harb Perspect Med. 2012;2(3):1–18.
Liu Y, Wu J, Huang W, Weng S, Wang B, Chen Y, et al. Development and validation of a hypoxia-immune-based microenvironment gene signature for risk stratification in gastric cancer. J Transl Med. 2020;18(1):1–17.
Macedo F, Ladeira K, Longatto-Filho A, Martins SF. Gastric cancer and angiogenesis: Is VEGF a useful biomarker to assess progression and remission? J Gastric Cancer. 2017;17(1):1–10.
Deng B, Zhu JM, Wang Y, Liu TT, Ding YB, Xiao WM, et al. Intratumor Hypoxia Promotes Immune Tolerance by Inducing Regulatory T Cells via TGF-β1 in Gastric Cancer. PLoS One. 2013;8(5):1–9.
Kheshtchin N, Arab S, Ajami M, Mirzaei R, Ashourpour M, Mousavi N, et al. Inhibition of HIF-1α enhances anti-tumor effects of dendritic cell-based vaccination in a mouse model of breast cancer. Cancer Immunol Immunother. 2016;65(10):1159–67.
Certo M, Tsai C-H, Pucino V, Ho P-C, Mauro C. Lactate modulation of immune responses in inflammatory versus tumour microenvironments. Nat Rev Immunol. 2020;1–11.
Wang Q, Zhu D. The prognostic value of systemic immune-inflammation index (SII) in patients after radical operation for carcinoma of stomach in gastric cancer. J Gastrointest Oncol. 2019;10(5):965–78
Sun X, Wang J, Liu J, Chen S, Liu X. Albumin concentrations plus neutrophil lymphocyte ratios for predicting overall survival after curative resection for gastric cancer. Onco Targets Ther. 2016 Jul 27;9:4661–9.
Yang L, Liu Q, Zhang X, Liu X, Zhou B, Chen J, et al. DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature. 2020;(July 2019):1–25.
Dunn GP, Bruce AT, Ikeda H, Lloyd OJ, Schreiber RD. Cancer Immunoediting: From Inmuno-Surveillance to Tumor Escape. Nat Immunol. 2002;3(11):85–99.
Mohri Y, Tanaka K, Ohi M, Yokoe T, Miki C, Kusunoki M. Prognostic significance of host- and tumor-related factors in patients with gastric cancer. World J Surg. 2010;34(2):285–90.
Lian L, Xia YY, Zhou C, Shen XM, Li XL, Han SG, et al. Application of platelet/lymphocyte and neutrophil/lymphocyte ratios in early diagnosis and prognostic prediction in patients with resectable gastric cancer. Cancer Biomarkers. 2015 Nov 24;15(6):899–907.
Kim EY, Lee JW, Yoo HM, Park CH, Song KY. The Platelet-to-Lymphocyte Ratio Versus Neutrophil-to-Lymphocyte Ratio: Which is Better as a Prognostic Factor in Gastric Cancer? Ann Surg Oncol. 2015 Dec 1;22(13):4363–70.
Kim JH, Han DS, Bang HY, Kim PS, Lee KY. Preoperative neutrophil-to-lymphocyte ratio is a prognostic factor for overall survival in patients with gastric cancer. Ann Surg Treat Res. 2015 Aug 1;89(2):81–6.
Roychoudhuri R, Eil RL, Restifo NP. The interplay of effector and regulatory T cells in cancer. Curr Opin Immunol. 2015;33:101–11.
Whiteside TL. The tumor microenvironment and its role in promoting tumor growth. Oncogene. 2008;27(45):5904–12.
Li Q, Peng K, Chen E, Jiang H, Wang Y, Yu S, et al. IntegrinB5 upregulated by HER2 in gastric cancer: a promising biomarker for liver metastasis. Ann Transl Med. 2020;8(7):451–451.
Desnoyers A, González C, Pérez-Segura P, Pandiella A, Amir E, Ocaña A. Integrin ανβ6 Protein Expression and Prognosis in Solid Tumors: A Meta-Analysis. Vol. 24, Molecular Diagnosis and Therapy. Adis; 2020. p. 143–51.
Cheng S, Li X, Yuan Y, Jia C, Chen L, Gao Q, et al. ITGB1 Enhances the Proliferation, Survival, and Motility in Gastric Cancer Cells. Microsc Microanal. 2021;27(5):1192–201.
Freitas D, Campos D, Gomes J, Pinto F, Macedo JA, Matos R, et al. O-glycans truncation modulates gastric cancer cell signaling and transcription leading to a more aggressive phenotype. EBioMedicine. 2019;40:349–62.
LIS H, SHARON N. Protein glycosylation: Structural and functional aspects. Eur J Biochem. 1993;218(1):1–27.
Wang S, Wu T, Lee C, Yu J. Dissecting the conformation of glycans and their interactions with proteins. J Biomed Sci. 2020;27(93):1–16.
Harvey DJ. Proteomic analysis of glycosylation: Structural determination of N- and O-linked glycans by mass spectrometry. Expert Rev Proteomics. 2005 Feb;2(1):87–101.
Fernandes E, Sores J, Cotton S, Peixoto A, Ferreira D, Freitas R, et al. Esophageal, gastric and colorectal cancers: Looking beyond classical serological biomarkers towards glycoproteomics-assisted precision oncology. Theranostics. 2020;10(11):4903–28.
Reindl J, Shevtsov M, Dollinger G, Stangl S, Multhoff G. Membrane Hsp70-supported cell-to-cell connections via tunneling nanotubes revealed by live-cell STED nanoscopy. Cell Stress Chaperones. 2019;213–21.
Trinchera M, Aronica A, Dall’Olio F. Selectin ligands Sialyl-Lewis a and Sialyl-Lewis x in gastrointestinal cancers. Biology (Basel). 2017;6(1):1–18.
Isomoto H, Oka M, Yano Y, Kanazawa Y, Soda H, Terada R, et al. Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer. Cancer Lett. 2003;198(2):219–28.
Berezowska S, Novotny A, Bauer K, Feuchtinger A, Slotta-Huspenina J, Becker K, et al. Association between HSP90 and Her2 in gastric and gastroesophageal carcinomas. PLoS One. 2013;8(7):e69098.
Kang GH, Lee EJ, Jang KT, Kim K-M, Park CK, Lee C-S, et al. Expression of HSP90 in gastrointestinal stromal tumours and mesenchymal tumours. Histopathology. 2010 May;56(6):694–701.
Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005;10(2):86–103.
Wang J, Cui S, Zhang X, Wu Y, Tang H. High Expression of Heat Shock Protein 90 Is Associated with Tumor Aggressiveness and Poor Prognosis in Patients with Advanced Gastric Cancer. PLoS One. 2013;8(4).
Chung YM, Park S, Park JK, Kim Y, Kang Y, Yoo YD. Establishment and characterization of 5-fluorouracil-resistant gastric cancer cells. Cancer Lett. 2000;159(1):95–101.
Pfister K, Radons J, Busch R, Tidball JG, Pfeifer M, Freitag L, et al. Patient survival by Hsp70 membrane phenotype: Association with different routes of metastasis. Cancer. 2007;110(4):926–35.
Wang FL, Cui SX, Sun LP, Qu XJ, Xie YY, Zhou L, et al. High expression of α 2, 3-linked sialic acid residues is associated with the metastatic potential of human gastric cancer. Cancer Epidemiol. 2009;32(5–6):437–43.
Sun X, Li D, Duan Z. Structural Basis of Glycan Recognition of Rotavirus. Front Mol Biosci. 2021;8(July):1–12.
Bertuzzi S, Quintana JI, Ardá A, Gimeno A, Jiménez-Barbero J. Targeting Galectins With Glycomimetics. Front Chem. 2020;8(593):1–17.
Liu Y, Meng H, Xu S, Qi X. Galectins for Diagnosis and Prognostic Assessment of Human Diseases: An Overview of Meta-Analyses. Med Sci Monit. 2020;26:e923901.
Wolf Y, Anderson AC, Kuchroo VK. TIM3 comes of age as an inhibitory receptor. Nat Rev Immunol. 2020;20(3):173–85.
Bacigalupo ML, Carabias P, Troncoso MF. Contribution of galectin-1, a glycan-binding protein, to gastrointestinal tumor progression. World J Gastroenterol. 2017;23(29):5266–81.
Long B, Yu Z, Zhou H, Ma Z, Ren Y, Zhan H, et al. Clinical characteristics and prognostic significance of galectins for patients with gastric cancer: A meta-analysis. Int J Surg. 2018;56(82):242–9.
Zhai E, Liang W, Lin Y, Huang L, He X, Cai S, et al. HSP70/HSP90-Organizing Protein Contributes to Gastric Cancer Progression in an Autocrine Fashion and Predicts Poor Survival in Gastric Cancer. Cell Physiol Biochem. 2018;47(2):879–92.
Datta D, Banerjee S, Ghosh A, Mustafi SB, Raha S. Involvement of Heat Shock Protein 70 (Hsp70) in Gastrointestinal Cancers. In: HSP70 in Human Diseases and Disorders. Springer Nature; 2018. p. 71–91.
Isomoto H, Oka M, Yano Y, Kanazawa Y, Soda H, Terada R, et al. Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer. Cancer Lett. 2003 Aug 1;198(2):219–28.
Ge H, Yan Y, Lingfei G, Fei T, Di W. Prognostic role of hsPs in human gastrointestinal cancer: a systematic review and meta-analysis. Onco Targets Ther. 2018;11(28):351–9.
Hoter A, El-Sabban ME, Naim HY. The HSP90 family: Structure, regulation, function, and implications in health and disease. Int J Mol Sci. 2018;19(9).
HW L, KM K. Clinical Significance of Heat Shock Protein 90α Expression as a Biomarker of Prognosis in Patients With Gastric Cancer. Niger J Clin Pract. 2019;22(12):1699–705.
Zhang L, Hou Y, Li N, Wu K, Zhai J. The influence of TXNDC5 gene on gastric cancer cell. J Cancer Res Clin Oncol. 2010;136(10):1497–505.
Wu J, Chen X, Wang X, Yu Y, Ren J, Xiao Y. ERp19 contributes to tumorigenicity in human gastric cancer by promoting cell growth , migration and invasion. 2015;6(14).
Leys CM, Nomura S, LaFleur BJ, Ferrone S, Kaminishi M, Montgomery E, et al. Expression and prognostic significance of prothymosin-α and ERp57 in human gastric cancer. Surgery. 2007;141(1):41–50.
Liu T, Liu D, Kong X, Dong M. Clinicopathological Significance of Heat Shock Protein (HSP) 27 Expression in Gastric Cancer: A Updated Meta-Analysis. Evidence-based Complement Altern Med. 2020;2020.
Song D, Guo M, Wu K, Hao J, Nie Y, Fan D. Silencing of ER-resident oxidoreductase PDIA3 inhibits malignant biological behaviors of multidrug-resistant gastric cancer. Acta Biochim Biophys Sin (Shanghai). 2021;53(9):1216–26.
Zhang D, Fan D. New insights into the mechanisms of gastric cancer multidrug resistance and future perspectives. Futur Oncol. 2010;6(4):527–37.
Arienti C, Pignatta S, Tesei A. Epidermal Growth Factor Receptor Family and its Role in Gastric Cancer. Front Oncol. 2019;9(November):1–11.
Zhang D, Fan D. Multidrug resistance in gastric cancer: recent research advances and ongoing therapeutic challenges. Expert Rev Anticancer Ther. 2007 Oct;7(10):1369–78.
Gambardella V, Castillo J, Tarazona N, Gimeno-Valiente F, Martínez-Ciarpaglini C, Cabeza M, et al. The role of Tumor-Associated Macrophages in Gastric Cancer development and their potential as a therapeutic target. Cancer Treat Rev. 2020;86(March):102015.
He X-J, Tao H-Q, Hu Z-M, Ma Y-Y, Xu J, Wang H-J, et al. Expression of galectin-1 in carcinoma-associated fibroblasts promotes gastric cancer cell invasion through upregulation of integrin β1. Cancer Sci. 2014;105(11):1402–10.
Shao D, Wang X, Li Z, Xing X, Cheng X, Guo T, et al. High-level SAE2 promotes malignant phenotype and predicts outcome in gastric cancer. Am J Cancer Res. 2015;5(2):589–602.
Herrmann K, Walch a, Balluff B, Tanzer M, Hofler H, Krause BJ, et al. Proteomic and metabolic prediction of response to therapy in gastrointestinal cancers. Nat Clin Pr Gastroenterol Hepatol. 2009;6(3):170–83.
Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): A double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct 1;15(11):1224–35.
Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, et al. Everolimus for previously treated advanced gastric cancer: Results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol. 2013;31(31):3935–43.
Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 3;383(9911):31–9.
Yang L, Wang Y, Wang H. Use of immunotherapy in the treatment of gastric cancer (Review). Oncol Lett. 2019;18(6):5681–90.
Giampieri R, Maccaroni E, Mandolesi A, Del Prete M, Andrikou K, Faloppi L, et al. Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy. Gastric Cancer. 2017;20(1):156–63.
Kang YK, Rha SY, Tassone P, Barriuso J, Yu R, Szado T, et al. A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. Br J Cancer. 2014;111(4):660–6.
Nie S, Yang G, Lu H. Current molecular targeted agents for advanced gastric cancer. Onco Targets Ther. 2020;13:4075–88.
Motoshima S, Yonemoto K, Kamei H, Morita M, Yamaguchi R. Prognostic implications of HER2 heterogeneity in gastric cancer. Oncotarget. 2018;9(10):9262–72.
Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, et al. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct 1;19(10):1372–84.
DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01] - Full Text View - ClinicalTrials.gov [Internet]. [cited 2020 Jun 17]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03329690
Han HS, Kim BJ, Jee H-J, Ryu M-H, Park SH, Rha SY, et al. Ramucirumab plus paclitaxel as second-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma: a nationwide real-world outcomes in Korea study (KCSG-ST19-16). Ther Adv Med Oncol. 2021;13:17588359211042812.
Li X, Zhu X, Wang Y, Wang R, Wang L, Zhu ML, et al. Prognostic value and association of lauren classification with vegf and vegfr-2 expression in gastric cancer. Oncol Lett. 2019;18(5):4891–9.
O’Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2019;16(3):151–67.
Petitprez F, Meylan M, de Reyniès A, Sautès-Fridman C, Fridman WH. The Tumor Microenvironment in the Response to Immune Checkpoint Blockade Therapies. Front Immunol. 2020;11(May):1–11.
Chen LT, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, et al. A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data. Gastric Cancer. 2020;23(3):510–9.
Xiang Z, Chen W, Zhang J, Song S, Xia GK, Huang XY, et al. Identification of discrepancy between CTLA4 expression and CTLA4 activation in gastric cancer. Immunopharmacol Immunotoxicol. 2019;41(3):386–93.
Gu L, Chen M, Guo D, Zhu H, Zhang W, Pan J, et al. PD-L1 and gastric cancer prognosis: A systematic review and meta-analysis. PLoS One. 2017;12(8):1–14.
Picardo SL, Doi J, Hansen AR. Structure and optimization of checkpoint inhibitors. Cancers (Basel). 2020;12(1):1–15.
Kulangara K, Hanks DA. Development of the combined positive score (CPS) for the evaluation of PD-L1 in solid tumors with the immunohistochemistry assay PD-L1 IHC 22C3 pharmDx. J Clin Oncol. 2017;25(15).
Bang YJ, Kang YK, Catenacci D V., Muro K, Fuchs CS, Geva R, et al. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer. 2019;22(4):828–37.
Mendis S, Gill S. Cautious optimism-the current role of immunotherapy in gastrointestinal cancers. Curr Oncol. 2020;27(April):S59–68.
Iwasa S, Kudo T, Takahari D, Hara H, Kato K, Satoh T. Practical guidance for the evaluation of disease progression and the decision to change treatment in patients with advanced gastric cancer receiving chemotherapy. Int J Clin Oncol. 2020;(Table 1).
Waddell T, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D. Gastric cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Eur J Surg Oncol. 2014;40(5):584–91.
Cao GD, He XB, Sun Q, Chen S, Wan K, Xu X, et al. The Oncolytic Virus in Cancer Diagnosis and Treatment. Front Oncol. 2020;10(September):1–12.
Jayawardena N, Poirier JT, Burga LN, Bostina M. Virus–Receptor Interactions and Virus Neutralization: Insights for Oncolytic Virus Development. Oncolytic Virotherapy. 2020;Volume 9:1–15.
Achard C, Surendran A, Wedge ME, Ungerechts G, Bell J, Ilkow CS. Lighting a Fire in the Tumor Microenvironment Using Oncolytic Immunotherapy. EBioMedicine. 2018;31:17–24.
Noonan AM, Farren MR, Geyer SM, Huang Y, Tahiri S, Ahn D, et al. Randomized Phase 2 Trial of the Oncolytic Virus Pelareorep (Reolysin) in Upfront Treatment of Metastatic Pancreatic Adenocarcinoma. Mol Ther. 2016;24(6):1150–8.
Workenhe ST, Mossman KL. Oncolytic Virotherapy and Immunogenic Cancer Cell Death: Sharpening the Sword for Improved Cancer Treatment Strategies. Mol Ther. 2013;22(2):251–6.
Alvarez-Breckenridge C a, Choi BD, Suryadevara CM, Chiocca EA. Potentiating oncolytic viral therapy through an understanding of the initial immune responses to oncolytic viral infection. Curr Opin Virol. 2015;13:25–32.
Guo ZS, Liu Z, Bartlett DL. Oncolytic Immunotherapy: Dying the Right Way is a Key to Eliciting Potent Antitumor Immunity. Front Oncol. 2014;4(April):1–11.
Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov. 2015;14(9).
Heiniö C, Havunen R, Santos J, Lint K de, Cervera-Carrascon V, Kanerva A, et al. TNFa and IL2 Encoding Oncolytic Adenovirus Activates Pathogen and Danger-Associated Immunological Signaling. Cells. 2020;9(4):1–13.
Pol J, Bloy N, Obrist F, Eggermont A, Galon J, Cremer I, et al. Trial Watch:: Oncolytic viruses for cancer therapy. Oncoimmunology. 2014;3(April):e28694.
Cattaneo R, Russell SJ. How to develop viruses into anticancer weapons. PLoS Pathog. 2017;13(3):8–13.
Garijo R, Hernández-Alonso P, Rivas C, Diallo JS, Sanjuán R. Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells. PLoS One. 2014;9(7):1–8.
Kaufman HL, Bommareddy PK. Two roads for oncolytic immunotherapy development. J Immunother Cancer. 2019;7(1):1–5.
Alberts P, Tilgase A, Rasa A, Bandere K, Venskus D. The advent of oncolytic virotherapy in oncology: The Rigvir® story. Eur J Pharmacol. 2018;837(August):117–26.
Liang M. Oncorine, the World First Oncolytic Virus Medicine and its Update in China. Curr Cancer Drug Targets. 2018;18(2):171–6.
Sugawara K, Iwai M, Yajima S, Tanaka M, Yanagihara K, Seto Y, et al. Efficacy of a Third-Generation Oncolytic Herpes Virus G47Δ in Advanced Stage Models of Human Gastric Cancer. Mol Ther oncolytics. 2020 Jun;17:205–15.
Medicine USNL of. https://clinicaltrials.gov [Internet]. 2022 [cited 2022 Jun 5]. Available from: https://clinicaltrials.gov
Gao P, Ding G, Wang L. The efficacy and safety of oncolytic viruses in the treatment of intermediate to advanced solid tumors: A systematic review and meta-analysis. Transa Cancer Res. 2021;10(10):4290–302.
Coffin RS. From virotherapy to oncolytic immunotherapy: where are we now? Curr Opin Virol. 2015;13:93–100.
Diccionario de cáncer del NCI - Instituto Nacional del Cáncer [Internet]. [cited 2020 Oct 17]. Available from: https://www.cancer.gov/espanol/publicaciones/diccionario/def/efecto-abscopal
Bishop RF, Davidson GP, Holmes IH, Ruck BJ. Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis. Lancet (London, England). 1973 Dec 8;2(7841):1281–3.
Desselberger U. Rotaviruses. Virus Res. 2014;190:75–96.
Hoshino Y, Sereno MM, Midthun K, Flores J, Kapikian AZ, Chanock RM. Independent segregation of two antigenic specificities (VP3 and VP7) involved in neutralization of rotavirus infectivity. Proc Natl Acad Sci U S A. 1985;82(24):8701–4.
Thomas RJ, Bartee E. The use of oncolytic virotherapy in the neoadjuvant setting. J Immunother Cancer. 2022;10:1–9.
Hoxie I, Dennehy JJ. Intragenic recombination influences rotavirus diversity and evolution. Virus Evol. 2020;6(1):1–16.
Crawford SE, Ramani S, Tate JE, Parashar UD, Svensson L, Hagbom M, et al. Rotavirus infection. Nat Rev Dis Prim. 2017;3(17083):1–16.
Flewett T, Bryden A, Davies H. VIRUS PARTICLES IN EPITHELIAL CELLS OF DUODENAL MUCOSA FROM CHILDREN WITH ACUTE NON-BACTERIAL GASTROENTERITIS. Lancet. 1973;302(7844):1497.
Amimo JO, Raev SA, Chepngeno J, Mainga AO, Guo Y, Saif L, et al. Rotavirus Interactions With Host Intestinal Epithelial Cells. Front Immunol. 2021;12(December):1–17.
Pesavento JB, Crawford SE, Estes MK, Prasad BVV. Rotavirus proteins: structure and assembly. Curr Top Microbiol Immunol. 2006;309:189–219.
Kumar D, Yu X, Crawford SE, Moreno R, Jakana J, Sankaran B, et al. 2.7 Å cryo-EM structure of rotavirus core protein VP3, a unique capping machine with a helicase activity. Sci Adv. 2020;6(16):1–10.
Feng N, Hu L, Ding S, Sanyal M, Zhao B, Sankaran B, et al. Human VP8* mAbs neutralize rotavirus selectively in human intestinal epithelial cells. J Clin Invest. 2019 Aug 13;129(9).
Arias CF, Silva-Ayala D, López S. Rotavirus Entry: a Deep Journey into the Cell with Several Exits. J Virol. 2015;89(November):890–3.
Trask SD, Ogden KM, Patton JT. Interactions among capsid proteins orchestrate rotavirus particle functions. Curr Opin Virol. 2012;2(4):373–9.
Aoki ST, Settembre E, Trask SD, Greenberg HB, Stephen C, Dormitzer PR. Structure of rotavirus outer-layer protein VP7 bound with a neutralizing Fab. Science (80- ). 2009;324(5933):1444–7.
King AMQ, Adams MJ, Lefkowitz EJ. Virus Taxonomy: Classification and Nomenclature of Viruses : Ninth Report of the International Committee on Taxonomy of Viruses. Elsevier; 2011. 1327 p.
Gautam R, Esona MD, Mijatovic-Rustempasic S, Ian Tam K, Gentsch JR, Bowen MD. Real-time RT-PCR assays to differentiate wild-type group A rotavirus strains from Rotarix(®) and RotaTeq(®) vaccine strains in stool samples. Hum Vaccin Immunother. 2013;10(3):767–77.
Gualtero DF, Guzmán F, Acosta O, Guerrero C a. Amino acid domains 280-297 of VP6 and 531-554 of VP4 are implicated in heat shock cognate protein hsc70-mediated rotavirus infection. Arch Virol. 2007;152:2183–96.
Suzuki H. Rotavirus replication: Gaps of knowledge on virus entry and morphogenesis. Tohoku J Exp Med. 2019;248(4):285–96.
Maruri-Avidal L, López S, Arias CF. Endoplasmic reticulum chaperones are involved in the morphogenesis of rotavirus infectious particles. J Virol. 2008;82(11):5368–80.
Coulson BS, Londrigan SL, Lee DJ. Rotavirus contains integrin ligand sequences and a disintegrin-like domain that are implicated in virus entry into cells. Proc Natl Acad Sci U S A. 1997;94(10):5389–94.
Guerrero C, Méndez E, Zárate S, Isa P, López S, Arias CF. Integrin alpha(v)beta(3) mediates rotavirus cell entry. Proc Natl Acad Sci U S A. 2000;97(26):14644–9.
Zárate S, Espinosa R, Romero P, Guerrero CA, Arias CF, López S. Integrin alpha2beta1 mediates the cell attachment of the rotavirus neuraminidase-resistant variant nar3. Virology. 2000;278(1):50–4.
Graham KL, Halasz P, Tan Y, Hewish MJ, Takada Y, Mackow ER, et al. Integrin-using rotaviruses bind alpha2beta1 integrin alpha2 I domain via VP4 DGE sequence and recognize alphaXbeta2 and alphaVbeta3 by using VP7 during cell entry. J Virol. 2003;77(18):9969–78.
Zárate S, Romero P, Espinosa R, Arias CF, López S. VP7 Mediates the Interaction of Rotaviruses with Integrin αvβ3 through a Novel Integrin-Binding Site. J Virol. 2004;78(20):10839–47.
Guerrero CA, Santana AY, Acosta O. Mouse intestinal villi as a model system for studies of rotavirus infection. J Virol Methods. 2010;168(1–2):22–30.
Arias CF, Isa P, Guerrero C a, Méndez E, Zárate S, López T, et al. Molecular biology of rotavirus cell entry. Arch Med Res. 2002;33(4):356–61
Pérez-Ortín R, Vila-Vicent S, Carmona-Vicente N, Santiso-Bellón C, Rodríguez-Díaz J, Buesa J. Histo-blood group antigens in children with symptomatic rotavirus infection. Viruses. 2019;11(4).
Acosta O, Calderon M, Moreno L, Guerrero C a. UN MODELO DEL MECANISMO DE ENTRADA DE LOS ROTAVIRUS A LA CÉLULA HOSPEDERA. Rev Fac Med Univ Nac Colomb. 2009;57(2):124–48.
Desselberger U, Richards J, Tchertanov L, Lepault J, Lever A, Burrone O, et al. Further characterisation of rotavirus cores: Ss(+)RNAs can be packaged in vitro but packaging lacks sequence specificity. Virus Res. 2013;178(2):252–63.
Chen D, Ramig RF. Rescue of infectivity by sequential in vitro transcapsidation of rotavirus core particles with inner capsid and outer capsid proteins. Virology. 1993 Jun;194(2):743–51.
Yoder JD, Trask SD, Vo PT, Binka M, Feng N, Harrison SC, et al. VP5* Rearranges when Rotavirus Uncoats. J Virol. 2009;83(21):11372–7.
Fleming FE, Bohm R, Dang VT, Holloway G, Haselhorst T, Madge PD, et al. Relative Roles of GM1 Ganglioside, N-Acylneuraminic Acids, and 2 1 Integrin in Mediating Rotavirus Infection. J Virol. 2014;88(8):4558–71.
Ciarlet M, Ludert JE, Iturriza-Gómara M, Liprandi F, Gray JJ, Desselberger U, et al. Initial interaction of rotavirus strains with N-acetylneuraminic (sialic) acid residues on the cell surface correlates with VP4 genotype, not species of origin. J Virol. 2002;76(8):4087–95.
Guo LA, Zhang M, Hou Y zhen, Hu H, Fang L, Tan M, et al. Epidemiology and HBGA-susceptibility investigation of a G9P[8] rotavirus outbreak in a school in Lechang, China. Arch Virol. 2020;165(6):1311–20.
Coulson BS. Expanding diversity of glycan receptor usage by rotaviruses. Curr Opin Virol. 2015 Dec;15:90–6.
Delorme C, Brüssow H, Teneberg S. Glycosphingolipid Binding Specificities of Rotavirus: Identification of a Sialic Acid-Binding Epitope ´. J Microbiol. 2001;75(5):2276–87.
Kun HR, Strains MO. Ganglioside GMi a on the Cell Surface Is Involved in the Infection by. 1999;688:683–8.
Pérez-Vargas J, Romero P, López S, Arias CF. The peptide-binding and ATPase domains of recombinant hsc70 are required to interact with rotavirus and reduce its infectivity. J Virol. 2006;80(7):3322–31.
Zárate S, Cuadras M a, Espinosa R, Romero P, Juárez KO, Camacho-Nuez M, et al. Interaction of rotaviruses with Hsc70 during cell entry is mediated by VP5. J Virol. 2003;77(13):7254–60.
Fleming FE, Graham KL, Takada Y, Coulson BS. Determinants of the specificity of rotavirus interactions with the alpha2beta1 integrin. J Biol Chem. 2011 Feb 25;286(8):6165–74.
Santana AY, Guerrero C a., Acosta O. Implication of Hsc70, PDI and integrin avb3 involvement during entry of the murine rotavirus ECwt into small-intestinal villi of suckling mice. Arch Virol. 2013;158(6):1323–36.
Torres-Flores JM, Silva-Ayala D, Espinoza M a., López S, Arias CF. The tight junction protein JAM-A functions as coreceptor for rotavirus entry into MA104 cells. Virology. 2015;475:172–8.
Patton JT, Hua J, Mansell EA. Location of intrachain disulfide bonds in the VP5* and VP8* trypsin cleavage fragments of the rhesus rotavirus spike protein VP4. J Virol. 1993;67(8):4848–55.
Calderón MN, Guerrero C a, Acosta O, Lopez S, Arias CF. Inhibiting Rotavirus Infection by Membrane- Impermeant Thiol / Disulfide Exchange Blockers and Antibodies against Protein Disulfide. Intervirology. 2012;55(3):451–64.
Calderón MN, Guerrero C a, Domínguez Y, Garzón E, Barreto SM, Acosta O. Interaction of rotavirus with protein disulfide isomerase in vitro and cell system [Interacción de rotavirus con la proteína disulfuro-isomerasa in vitro y en sistemas celulares]. Biomedica. 2011;31(1):70–81.
Settembre EC, Chen JZ, Dormitzer PR, Grigorieff N, Harrison SC. Atomic model of an infectious rotavirus particle. EMBO J. 2011;30(2):408–16.
Dormitzer PR, Sun ZYJ, Wagner G, Harrison SC. The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site. EMBO J. 2002;21(5):885–97.
Trask SD, McDonald SM, Patton JT. Structural Insights into the Coupling of Virion Assembly and Rotavirus Replication. Nat Rev Microbiol. 2013;10(3):165–77.
Silva-Ayala D, López T, Gutiérrez M, Perrimon N, López S, Arias CF. Genome-wide RNAi screen reveals a role for the ESCRT complex in rotavirus cell entry. Proc Natl Acad Sci U S A. 2013;110(25):10270–5.
Santoro MG, Amici C, Rossi A. Role of Heat Shock Proteins in Viral Infection. In: Pockley A., Calderwood S. SM, editor. Prokaryotic and Eukaryotic Heat Shock Proteins in Infectious Disease Heat Shock Proteins. 4th ed. Springer; 2009. p. 51–84.
Ogden KM, Snyder MJ, Dennis AF, Patton JT. Predicted Structure and Domain Organization of Rotavirus Capping Enzyme and Innate Immune Antagonist VP3. J Virol. 2014;88(16):9072–85.
Piron M, Vende P, Cohen J, Poncet D. Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A) binding protein from eIF4F. EMBO J. 1998;17(19):5811–21.
Vende P, Piron M, Castagné N, Poncet D. Efficient Translation of Rotavirus mRNA Requires Simultaneous Interaction of NSP3 with the Eukaryotic Translation Initiation Factor eIF4G and the mRNA 3′ End. J Virol. 2000;74(15):7064–71.
Arnold MM. The Rotavirus Interferon Antagonist NSP1: Many Targets, Many Questions. J Virol. 2016;90(11):5212–5.
Gratia M, Sarot E, Vende P, Charpilienne A, Baron CH, Duarte M, et al. Rotavirus NSP3 Is a Translational Surrogate of the Poly(A) Binding Protein-Poly(A) Complex. J Virol. 2015 Sep 1;89(17):8773–82.
Glück S, Buttafuoco A, Meier AF, Arnoldi F, Vogt B, Schraner EM, et al. Rotavirus replication is correlated with S/G2 interphase arrest of the host cell cycle. PLoS One. 2017;12(6):1–24.
Ball JM, Mitchell DM, Gibbons TF, Parr RD. Review Rotavirus NSP4: A Multifunctional Viral Enterotoxin. VIRAL Immunol. 2005;18(1):27–40.
Eichwald C, Arnoldi F, Laimbacher AS, Schraner EM, Fraefel C, Wild P, et al. Rotavirus viroplasm fusion and perinuclear localization are dynamic processes requiring stabilized microtubules. PLoS One. 2012;7(10):e47947.
Suárez YG, Martínez JL, Hernández DT, Hernández HO, Pérez-Delgado A, Méndez M, et al. Nanoscale organization of rotavirus replication machineries. Elife. 2019;8:1–53.
Crawford SE, Desselberger U. Lipid droplets form complexes with viroplasms and are crucial for rotavirus replication. Curr Opin Virol. 2016;19:11–5.
López T, Camacho M, Zayas M, Nájera R, Sánchez R, Arias CF, et al. Silencing the Morphogenesis of Rotavirus. J Virol. 2005;79(1):184–92.
Carreño-Torres JJ, Gutiérrez M, Arias CF, López S, Isa P. Characterization of viroplasm formation during the early stages of rotavirus infection. Virol J. 2010;7(1):350.
Viskovska M, Anish R, Hu L, Chow D-C, Hurwitz AM, Brown NG, et al. Probing the sites of interactions of rotaviral proteins involved in replication. J Virol. 2014;88(21):12866–81.
Bennett J, Dolin R, Blaser M. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Elsevier Inc; 2015. 1857–1858 p.
Qin L, Ren L, Zhou Z, Lei X, Chen L, Xue Q, et al. Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I. Virol J. 2011;8:526.
Davis CA, Morelli KA, Patton MT. Rotavirus NSP1 Requires Casein Kinase II-Mediated Phosphorylation for Hijacking of Cullin-RING Ligases. MBio. 2017;8(4):1213–30.
Sastri NP, Viskovska M, Hyser JM, Tanner MR, Horton LB, Sankaran B, et al. Structural Plasticity of the Coiled-Coil Domain of Rotavirus NSP4. J Virol. 2014;88(23):13602–12.
Crawford SE, Criglar JM, Liu Z, Broughman JR, Estes MK. COPII Vesicle Transport Is Required for Rotavirus NSP4 Interaction with the Autophagy Protein LC3 II and Trafficking to Viroplasms. J Virol. 2019;94(1):1–14.
Razavinikoo H, Soleimanjahi H, Haqshenas G, Bamdad T, Goodarzi Z. Activation of calcium / calmodulin-dependent kinase following bovine rotavirus enterotoxin NSP4 expression. Iran J Basic Med Sci. 2015;18(4):2–6.
Seo N-S, Zeng CQ-Y, Hyser JM, Utama B, Crawford SE, Kim KJ, et al. Integrins alpha1beta1 and alpha2beta1 are receptors for the rotavirus enterotoxin. Proc Natl Acad Sci U S A. 2008;105(26):8811–8.
Hu L, Crawford SE, Hyser JM, Estes MK, Prasad BVVV. Rotavirus non-structural proteins : Structure and Function. Curr Opin Virol. 2012;2(4):380–8.
Rivera M, Guerrero CA, Acosta O. Thiol/disulfide exchange occurs in rotavirus structural proteins during contact with intestinal villus cell surface. Acta Virol. 2020;64(1):44–58.
Rico J, Perez C, Hernandez J, Guerrero C, Acosta O. Cell surface heat shock protein-mediated entry of tumor cell-adapted rotavirus into U-937 cells. Folia Microbiol (Praha). 2021;(0123456789).
Rico J, Perez C, Guerrero R, Hernandez J, Guerrero C, Acosta O. Implication of heat shock proteins in rotavirus entry into Reh cells. Acta Virol. 2020;64(4):433–50.
Perez C, Rico J, Guerrero C, Acosta O. Role of heat-shock proteins in infection of human adenocarcinoma cell line MCF-7 by tumor-adapted rotavirus isolates. Colomb medica (Cali, Colomb. 2021;52(1):e2024196.
Guerrero R, Guerrero C, Acosta O. Induction of cell death in the human acute lymphoblastic leukemia cell line reh by infection with rotavirus isolate Wt1-5. Vol. 8, Biomedicines. 2020. 1–33 p.
Liou GY, Storz P. Reactive oxygen species in cancer. Vol. 44, Free Radical Research. 2010.
Yang H, Villani RM, Wang H, Simpson MJ, Roberts MS, Tang M, et al. The role of cellular reactive oxygen species in cancer chemotherapy. Vol. 37, Journal of Experimental and Clinical Cancer Research. 2018.
Guerrero CA, Bouyssounade D, Zárate S, Iša P, López T, Espinosa R, et al. Heat Shock Cognate Protein 70 Is Involved in Rotavirus Cell Entry. J Virol. 2002;76(8):4096–102.
Arias CF, López S. Rotavirus cell entry: not so simple after all. Curr Opin Virol. 2021;48:42–8.
Abdelhakim AH, Salgado EN, Fu X, Pasham M, Nicastro D, Kirchhausen T, et al. Structural Correlates of Rotavirus Cell Entry. PLoS Pathog. 2014;10(9):e1004355.
Jiang Y, Zhang Q, Hu Y, Li T, Yu J, Zhao L, et al. ImmunoScore Signature: A Prognostic and Predictive Tool in Gastric Cancer. Ann Surg. 2018;267(3):504–13.
Song Z, Wu Y, Yang J, Yang D, Fang X. Progress in the treatment of advanced gastric cancer. Tumor Biol. 2017;39(7).
Sanjuán R, Grdzelishvili VZ. Evolution of oncolytic viruses. Curr Opin Virol. 2015;13:1–5.
Hu B, El Hajj N, Sittler S, Lammert N, Barnes R, Meloni-Ehrig A. Gastric cancer: Classification, histology and application of molecular pathology. J Gastrointest Oncol. 2012;3(3):251–61.
Arnold M, Patton JT, McDonald SM. Culturing, storage, and quantification of rotaviruses. Current Protocols in Microbiology. 2009. p. 1–29.
Diallo JS, Roy D, Abdelbary H, de Silva N, Bell JC. Ex vivo infection of live tissue with oncolytic viruses. J Vis Exp. 2011;(52):2–6.
Introini A, Vanpouille C, Fitzgerald W, Broliden K, Margolis L. Ex vivo infection of human lymphoid tissue and female genital mucosa with human immunodeficiency virus 1 and histoculture. J Vis Exp. 2018;2018(140).
Varghese F, Bukhari AB, Malhotra R, De A. IHC profiler: An open source plugin for the quantitative evaluation and automated scoring of immunohistochemistry images of human tissue samples. PLoS One. 2014;9(5):1–11.
Seyed Jafari SM, Hunger RE. IHC optical density score: A new practical method for quantitative immunohistochemistry image analysis. Appl Immunohistochem Mol Morphol. 2017;25(1):e12–3.
Lin PH, Selinfreund R, Wakshull E, Wharton W. Rapid and Efficient Purification of Plasma Membrane from Cultured Cells: Characterization of Epidermal Growth Factor Binding. Biochemistry. 1987;26(3):731–6.
Seymour LW, Fisher KD. Oncolytic viruses: finally delivering. Br J Cancer. 2016;114:357–61.
López S, Arias CF. Multistep entry of rotavirus into cells: A Versaillesque dance. Trends Microbiol. 2004;12(6):271–8.
Graham KL, Halasz P, Tan Y, Hewish MJ, Takada Y, Mackow ER, et al. Integrin-using rotaviruses bind alpha2beta1 integrin alpha2 I domain via VP4 DGE sequence and recognize alphaXbeta2 and alphaVbeta3 by using VP7 during cell entry. J Virol. 2003;77(18):9969–78.
Vousden KH, Lu X. Live or let die: The cell’s response to p53. Nat Rev Cancer. 2002;2(8):594–604.
Aubrey BJ, Kelly GL, Janic A, Herold MJ, Strasser A. How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ. 2018;25(1):104–13.
Gryko M, Pryczynicz A, Zareba K, Kȩdra B, Kemona A, Guzińska-Ustymowicz K. The expression of Bcl-2 and BID in gastric cancer cells. J Immunol Res. 2014;2014:1–5.
Holloway G, Coulson BS. Innate cellular responses to rotavirus infection. J Gen Virol. 2013;94(PART 6):1151–60.
Hundahl SA, Phillips JL, Menck HR. The National Cancer Data Base report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy. Cancer. 2000;88(4):921–32.
Izumi D, Nunobe S. How to Decide Approaches and Procedures for Early and Advanced Gastric Cancer ? Can J Gastroenterol Hepatol. 2022;2022:1–5.
Fouad YA, Aanei C. Revisiting the hallmarks of cancer. Am J Cancer Res. 2017;7(5):1016–36.
Breitbach CJ, Paterson JM, Lemay CG, Falls TJ, McGuire A, Parato KA, et al. Targeted inflammation during oncolytic virus therapy severely compromises tumor blood flow. Mol Ther. 2007;15(9):1686–93.
Kloker L, Yurttas C, Lauer U. Three-dimensional tumor cell cultures employed in virotherapy research. Oncolytic Virotherapy. 2018;Volume 7:79–93.
Breitbach CJ, De Silva NS, Falls TJ, Aladl U, Evgin L, Paterson J, et al. Targeting tumor vasculature with an oncolytic virus. Mol Ther. 2011;19(5):886–94.
Kooti W, Esmaeili Gouvarchin Ghaleh H, Farzanehpour M, Dorostkar R, Jalali Kondori B, Bolandian M. Oncolytic Viruses and Cancer, Do You Know the Main Mechanism? Front Oncol. 2021;11(December):1–11.
Khan HA, Mutus B. Protein disulfide isomerase a multifunctional protein with multiple physiological roles. Front Chem. 2014;2(AUG):1–9.
Giaginis C, Daskalopoulou SS, Vgenopoulou S, Sfiniadakis I, Kouraklis G, Theocharis SE. Heat Shock Protein-27, -60 and -90 expression in gastric cancer: Association with clinicopathological variables and patient survival. BMC Gastroenterol. 2009;9:1–10.
Geyer PE, Maak M, Nitsche U, Perl M, Novotny A, Slotta-Huspenina J, et al. Gastric adenocarcinomas express the glycosphingolipid Gb3/CD77: Targeting of gastric cancer cells with Shiga toxin B-subunit. Mol Cancer Ther. 2016;15(5):1008–17.
Elmallah MIY, Cordonnier M, Vautrot V, Chanteloup G, Garrido C, Gobbo J. Membrane-anchored heat-shock protein 70 (Hsp70) in cancer. Cancer Lett. 2020;469(August 2019):134–41.
Goodarzi Z, Soleimanjahi H, Arefian E, Saberfar E. The effect of bovine rotavirus and its nonstructural protein 4 on ER stress-mediated apoptosis in HeLa and HT-29 cells. Tumor Biol. 2015 Oct 1;37(3):3155–61.
Zhou Y, Frey TK, Yang JJ. Viral calciomics: Interplays between Ca2+ and virus. Cell Calcium. 2009;46(1):1–17.
Martin-Latil S, Mousson L, Autret A, Colbère-Garapin F, Blondel B. Bax is activated during rotavirus-induced apoptosis through the mitochondrial pathway. J Virol. 2007 May;81(9):4457–64.
Mukherjee A, Patra U, Bhowmick R, Chawla-Sarkar M. Rotaviral nonstructural protein 4 triggers dynamin-related protein 1-dependent mitochondrial fragmentation during infection. Cell Microbiol. 2018 Jun;20(6):e12831
Chattopadhyay S, Mukherjee A, Patra U, Bhowmick R, Basak T, Sengupta S, et al. Tyrosine phosphorylation modulates mitochondrial chaperonin Hsp60 and delays rotavirus NSP4-mediated apoptotic signaling in host cells. Cell Microbiol. 2017 Mar;19(3).
Vojtěšek B, Bártek J, Midgley CA, Lane DP. An immunochemical analysis of the human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods. 1992;151(1–2).
Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene. 2003;22(56 REV. ISS. 8):9030–40.
Bhowmick R, Halder UC, Chattopadhyay S, Nayak MK, Chawla-Sarkar M. Rotavirus-Encoded Nonstructural Protein 1 Modulates Cellular Apoptotic Machinery by Targeting Tumor Suppressor Protein p53. J Virol. 2013;87(12):6840–50.
Perez JF, Chemello ME, Liprandi F, Ruiz M-C, Michelangeli F. Oncosis in MA104 Cells Is Induced by Rotavirus Infection through an Increase in Intracellular Ca2 + Concentration. Virology. 1998;252:17–27.
Somersan S, Larsson M, Fonteneau JF, Basu S, Srivastava P, Bhardwaj N. Primary Tumor Tissue Lysates Are Enriched in Heat Shock Proteins and Induce the Maturation of Human Dendritic Cells. J Immunol. 2001;167(9):4844–52.
Sen A, Ding S GB. The Role of Innate Immunity in Regulating Rotavirus Replication, Pathogenesis, and Host Range Restriction and the Implications for Live Rotaviral Vaccine Development. Mucosal Vaccines. 2020;(January):683–97.
Di Fiore IJM, Holloway G, Coulson BS. Innate immune responses to rotavirus infection in macrophages depend on MAVS but involve neither the NLRP3 inflammasome nor JNK and p38 signaling pathways. Virus Res. 2015;208.
Narváez CF, Angel J, Franco MA. Interaction of Rotavirus with Human Myeloid Dendritic Cells. J Virol. 2005;79(23).
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.license.spa.fl_str_mv Reconocimiento 4.0 Internacional
dc.rights.uri.spa.fl_str_mv http://creativecommons.org/licenses/by/4.0/
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv Reconocimiento 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv 162 páginas
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Universidad Nacional de Colombia
dc.publisher.program.spa.fl_str_mv Bogotá - Ciencias - Doctorado en Biotecnología
dc.publisher.faculty.spa.fl_str_mv Facultad de Ciencias
dc.publisher.place.spa.fl_str_mv Bogotá,Colombia
dc.publisher.branch.spa.fl_str_mv Universidad Nacional de Colombia - Sede Bogotá
institution Universidad Nacional de Colombia
bitstream.url.fl_str_mv https://repositorio.unal.edu.co/bitstream/unal/83759/1/license.txt
https://repositorio.unal.edu.co/bitstream/unal/83759/2/79564678.2022.pdf
https://repositorio.unal.edu.co/bitstream/unal/83759/3/79564678.2022.pdf.jpg
bitstream.checksum.fl_str_mv eb34b1cf90b7e1103fc9dfd26be24b4a
caa5433f1cfdb45b21805abe3d23936d
c4867b618b5a9e6bde4426842b975e48
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
repository.mail.fl_str_mv repositorio_nal@unal.edu.co
_version_ 1814089721228296192
spelling Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Guerrero Fonseca, Carlos Arturocdd4ab53ceaeef988597f7e1a5dcf0b9Sossa Rojas, Henry36c0de453c5e911e44de83e407d09aecBiología CelularBiología Molecular de VirusBiotecnología Microbiana0000-0001-7854-06892023-04-24T13:40:56Z2023-04-24T13:40:56Z2022-07-01https://repositorio.unal.edu.co/handle/unal/83759Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.coilustraciones, fotografías a colorA pesar de los avances en la investigación en ciencias biomédicas, el cáncer gástrico sigue siendo una de las principales causas de morbilidad y mortalidad en el mundo debido a la limitada eficacia de las terapias convencionales. El objetivo de este estudio fue examinar el potencial oncolítico del aislamiento rotaviral Wt1-5 en muestras de adenocarcinomas gástricos obtenidas de seis pacientes sometidos a gastrectomías radicales en el Hospital Universitario de la Samaritana. Para lograrlo, se evaluó la capacidad del rotavirus para propagarse en el tumor y la importancia de la expresión de las proteínas correceptoras de membrana citoplasmática αVβ3, PDI, Hsc70, Hsp90, Hsp70, Hsp60 y Hsp40 durante la infección de las células tumorales. Se encontró que estas proteínas se expresan de forma diferencial en las células tumorales en comparación con el tejido no tumoral adyacente y que las células neoplásicas se infectaron significativamente en comparación con el tejido no tumoral adyacente, lo que inicio un efecto oncolítico. A las 12 h.p.i, se observó que la apoptosis era uno de los tipos de muerte que se evidenciaba al evaluar la expresión de caspasa 3, caspasa 9, PARP, citocromo C, BAX, BID, p53 y Bcl-2, así como al observar cambios morfológicos, como la marginación de la cromatina, condensación y fragmentación nuclear. Finalmente, en las horas posteriores a la infección (60 h.p.i), se observó una oncólisis que comprometió todo el espesor del tumor. En consecuencia, los resultados de este trabajo sugieren que el RV Wt1-5 puede ser una terapia coadyuvante a las terapias convencionales y/o terapias dirigidas en el manejo del cáncer gástrico. Además, la infección ex vivo del modelo de tejido tumoral también mostró características de respuesta inmune que pueden explorarse en estudios futuros. (Texto tomado de la fuente)Despite advances in biomedical science research, gastric cancer remains one of the leading causes of morbidity and mortality worldwide due to the limited efficacy of conventional therapies. The aim of this study was to examine the oncolytic potential of the rotaviral Wt1-5 isolate in gastric adenocarcinoma simples obtained from six patients undergoing radical gastrectomies at the Hospital Universitario de la Samaritana. To achieve this, the ability of the rotavirus to propagate in the tumor and the importance of the expression of the cytoplasmic membrane coreceptor proteins αVβ3, PDI, Hsc70, Hsp90, Hsp70, Hsp60, and Hsp40 during tumor cell infection were evaluated. It was found that these proteins were differentially expressed in tumor cells compared to adjacent non-tumor tissue, and neoplastic cells were significantly infected compared to adjacent non-tumor tissue, initiating an oncolytic effect. At 12 h.p.i, apoptosis was observed as one of the types of cell death, evidenced by the expression of caspase 3, caspase 9, PARP, cytochrome C, BAX, BID, p53, and Bcl-2, as well as morphological changes such as chromatin margination, condensation, and nuclear fragmentation. Finally, in the hours following infection (60 h.p.i), complete oncotic destruction of the tumor thickness was observed. Consequently, the results of this work suggest that RV Wt1-5 may be an adjuvant therapy to conventional and/or targeted therapies in the management of gastric cancer. In addition, ex vivo infection of the tumor tissue model also showed characteristics of immune response that can be explored in future studies.DoctoradoVirus Oncolíticos162 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Doctorado en BiotecnologíaFacultad de CienciasBogotá,ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::615 - Farmacología y terapéutica610 - Medicina y salud::611 - Anatomía humana, citología, histología610 - Medicina y salud::616 - EnfermedadesNeoplasias gástricasGastrectomíaStomach NeoplasmsGastrectomyRotavirusTerapia viral oncolíticaCáncer gástricoApoptosisLisis tumoralRotavirusOncolytic viral therapyGastric cancerApoptosisTumor lysisEstudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástricoOncolytic potential of human rotaviral isolation Wt 1-5 in gastric adenocarcinomaTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_db06Texthttp://purl.org/redcol/resource_type/TDSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49.International Agency for Research on Cancer. CANCER TODAY [Internet]. World Health Organization. [cited 2020 Dec 16]. Available from: https://gco.iarc.fr/today/homePardo C, Vries EDE, Buitrago L, Gamboa O. Atlas de mortalidad por cáncer en Colombia. 4th ed. Cancerologia IN de, editor. Bogota: Instituto Nacional de Cancerologia; 2017. 124 p.Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21(5):449–56.Naghavi M, Wang H, Lozano R, Davis A, Liang X, Zhou M, et al. Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385(9963):117–71.DIgklia A, Wagner AD. Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroenterol. 2016;22(8):2403–14.Guo Q, Jing FJ, Qu HJ, Xu W, Han B, Xing XM, et al. Ubenimex Reverses MDR in Gastric Cancer Cells by Activating Caspase-3-Mediated Apoptosis and Suppressing the Expression of Membrane Transport Proteins. Biomed Res Int. 2019;2019.Smyth EC, Moehler M. Late-line treatment in metastatic gastric cancer: today and tomorrow. Ther Adv Med Oncol. 2019;11:1–11.Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18(3):197–218.Russell SJ, Peng KW. Viruses as anticancer drugs. Trends Pharmacol Sci. 2007;28(7):326–33.Lowy D. NCI Dictionary of Cancer Terms - National Cancer Institute [Internet]. National Cancer Institute - at the National Institiutes of Health. [cited 2015 Nov 4]. Available from: http://www.cancer.gov/dictionary?cdrid=46216Chiocca EA, Rabkin SD. Oncolytic Viruses and Their Application to Cancer Immunotherapy. Cancer Immunol Res. 2014;2(4):295–300.Zhou J, Wang G, Chen Y, Wang H, Hua Y, Cai Z. Immunogenic cell death in cancer therapy: Present and emerging inducers. J Cell Mol Med. 2019;23(8):4854–65.Guo ZS, Liu Z, Kowalsky S, Feist M, Kalinski P, Lu B, et al. Oncolytic immunotherapy: Conceptual evolution, current strategies, and future perspectives. Front Immunol. 2017;8(555):1–15.Bommareddy PK, Shettigar M, Kaufman HL. Integrating oncolytic viruses in combination cancer immunotherapy. Nat Rev Immunol. 2018;18(August):1–16.International Committee on Taxonomy of Viruses (ICTV) [Internet]. [cited 2020 Oct 24]. Available from: https://talk.ictvonline.org/taxonomy/Matthijnssens J, Otto PH, Ciarlet M, Desselberger U, van Ranst M, Johne R. VP6-sequence-based cutoff values as a criterion for rotavirus species demarcation. Arch Virol. 2012;157(6):1177–82.Matthijnssens J, Ciarlet M, Rahman M, Attoui H, Estes MK, Gentsch JR, et al. Recommendations for the classification of group A rotaviruses using all 11 genomic RNA segments. Arch Virol. 2009;153(8):1621–9.Contreras-Treviño HI, Reyna-Rosas E, León-Rodríguez R, Ruiz-Ordaz BH, Dinkova TD, Cevallos AM, et al. Species A rotavirus NSP3 acquires its translation inhibitory function prior to stable dimer formation. PLoS One. 2017;12(7):1–18.Esona MD, Gautam R. Rotavirus. Clin Lab Med. 2015;35(2):363–91.Rojas M, Ayala-Breton C, Lopez S. BIOLOGÍA MOLECULAR DE ROTAVIRUS : UNA MIRADA A TRAVÉS DE LA INTERFERENCIA DE RNA. MENSAJE BIOQUÍMICO. 2008;XXXII:149–62.Matthijnssens J, Ciarlet M, McDonald SM, Attoui H, Bányai K, Brister JR, et al. Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG). Arch Virol. 2011;156(8):1397–413.Morelli M, Ogden KM, Patton JT. Silencing the alarms: Innate immune antagonism by rotavirus NSP1 and VP3. Virology. 2015;479-480C:75–84.Yu X, Blanchard H. Carbohydrate recognition by rotaviruses. J Struct Funct Genomics. 2014;15(3):101–6.Giaginis C, Daskalopoulou SS, Vgenopoulou S, Sfiniadakis I, Kouraklis G, Theocharis SE. Heat Shock Protein-27, -60 and -90 expression in gastric cancer: association with clinicopathological variables and patient survival. BMC Gastroenterol. 2009;9(14):1–10.Sharma PC, Verma R. Implication of HSP70 in the Pathogenesis of Gastric Cancer. In: HSP70 in Human Diseases and Disorders. Springer Nature; 2018. p. 113–30.Moreira AM, Pereira J, Melo S, Fernandes MS, Carneiro P, Seruca R, et al. The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression. Cells. 2020;9(2):394.Xu YH, Li ZL, Qiu SF. IFN-γ Induces Gastric Cancer Cell Proliferation and Metastasis Through Upregulation of Integrin β3-Mediated NF-κB Signaling. Transl Oncol. 2018;11(1):182–92.Wu Z, Zhang L, Li N, Sha L, Zhang K. An immunohistochemical study of thioredoxin domain-containing 5 expression in gastric adenocarcinoma. Oncol Lett. 2015;9(3):1154–8.Shimoda T, Wada R, Kure S, Ishino K, Kudo M, Ohashi R, et al. Expression of protein disulfide isomerase A3 and its clinicopathological association in gastric cancer. Oncol Rep. 2019;41(4):2265–72.Guerrero CA, Guerrero RA, Silva E, Acosta O, Barreto E. Experimental Adaptation of Rotaviruses to Tumor Cell Lines. PLoS One. 2016;11(2):1–25Guerrero C a, Bouyssounade D, Zárate S, Isa P, López T, Espinosa R, et al. Heat Shock Cognate Protein 70 Is Involved in Rotavirus Cell Entry Heat Shock Cognate Protein 70 Is Involved in Rotavirus Cell Entry. J Virol. 2002;76(8):4096–102.Santana AY, Guerrero CA, Acosta O. Implication of Hsc70, PDI and integrin αvβ3 involvement during entry of the murine rotavirus ECwt into small-intestinal villi of suckling mice. Arch Virol. 2013;158(6):1323–36.Guerrero RA, Guerrero CA, Guzmán F, Acosta O. Assessing the oncolytic potential of rotavirus on mouse myeloma cell line Sp2/0-Ag14. Biomedica. 2020;40(2).Laurén P. the Two Histological Main Types of Gastric Carcinoma: Diffuse and So-Called Intestinal-Type Carcinoma. an Attempt At a Histo-Clinical Classification. Acta Pathol Microbiol Scand. 1965;64:31–49.Pinho SS, Carvalho S, Marcos-Pinto R, Magalhães A, Oliveira C, Gu J, et al. Gastric cancer: Adding glycosylation to the equation. Trends Mol Med. 2013;19(11):664–76.Kang SH, Kim JS, Moon HS, Lee ES, Kim SH, Sung JK, et al. Signet ring cell carcinoma of early gastric cancer, is endoscopic treatment really risky? Medicine (Baltimore). 2017;96(33):1–5.Ohtsuka J, Oshima H, Ezawa I, Abe R, Oshima M, Ohki R. Functional loss of p53 cooperates with the in vivo microenvironment to promote malignant progression of gastric cancers. Sci Rep. 2018;8(1):1–15.Pan X, Ji X, Zhang R, Zhou Z, Zhong Y, Peng W, et al. Landscape of somatic mutations in gastric cancer assessed using next-generation sequencing analysis. Oncol Lett. 2018;16(4):4863–70.Li W, Luo S, Ma G, Wang L. <p>Impact of liver kinase B1 on p53 and survivin and its correlation with prognosis in gastric cancer</p>. Onco Targets Ther. 2019;Volume 12:1439–45.Yildirim M, Kaya V, Demirpence O, Gunduz S, Bozcuk H. Prognostic significance of p53 in gastric cancer: A meta-analysis. Asian Pacific J Cancer Prev. 2015;16(1):327–32.Lee JY, Gong EJ, Chung EJ, Park HW, Bae SE, Kim EH, et al. The characteristics and prognosis of diffuse-type early gastric cancer diagnosed during health check-ups. Gut Liver. 2017;11(6):807–12.Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison’s Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2). McGraw Hill Higher Education. 2018.Ma J, Shen H, Kapesa L, Zeng S. Lauren classification and individualized chemotherapyin gastric cancer (Review). Oncol Lett. 2016;11(5):2959–64Singh SR. Gastric cancer stem cells: a novel therapeutic target. Cancer Lett. 2013 Sep 10;338(1):110–9.Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev. 2014;23(5):700–13.Nakamura K, Sugano H, Takagi K. Carcinoma of the stomach in incipient phase: its histogenesis and histological appearances. Gan. 1968;59(3):251–8.Pernot S, Voron T, Perkins G, Lagorce-Pages C, Berger A, Taieb J. Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge. World J Gastroenterol. 2015;21(40):11428–38.Lai JF, Xu WN, Noh SH, Lu WQ. Effect of world health organization (WHO) histological classification on predicting lymph node metastasis and recurrence in early gastric cancer. Med Sci Monit. 2016;22:3147–53.Mahadevan V. Anatomy of the stomach. Surg (United Kingdom). 2017;35(11):608–11.Nie S, Yuan Y. The Role of Gastric Mucosal Immunity in Gastric Diseases. J Immunol Res. 2020;2020:1–8.Liu JY, Peng CW, Yang XJ, Huang CQ, Li Y. The prognosis role of AJCC/UICC 8th edition staging system in gastric cancer, a retrospective analysis. Am J Transl Res. 2018;10(1):292–303.Escrig Sos J, Gómez Quiles L, Maiocchi K. The 8th edition of the AJCC-TNM classification: New contributions to the staging of esophagogastric junction cancer. Cir Esp. 2019;97(8):432–7.Wang FH, Shen L, Li J, Zhou ZW, Liang H, Zhang XT, et al. The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer. Cancer Commun. 2019;39(1):1–31.Rodriquenz MG, Roviello G, D’Angelo A, Lavacchi D, Roviello F, Polom K. MSI and EBV Positive Gastric Cancer’s Subgroups and Their Link With Novel Immunotherapy. J Clin Invest. 2020;9(1427):1–12.Ham IH, Lee D, Hur H. Role of cancer-associated fibroblast in gastric cancer progression and resistance to treatments. J Oncol. 2019;2019:1–11.Angell HK, Bruni D, Carl Barrett J, Herbst R, Galon J. The immunoscore: Colon cancer and beyond a C. Clin Cancer Res. 2020;26(2):332–9.Chia NY, Tan P. Molecular classification of gastric cancer. Ann Oncol. 2016;27(5):763–9.Wang X, Mao M, Zhu S, Xing S, Song Y, Zhang L, et al. A Novel Nomogram Integrated with Inflammation-Based Factors to Predict the Prognosis of Gastric Cancer Patients. Adv Ther. 2020Link A, Kupcinskas J. MicroRNAs as non-invasive diagnostic biomarkers for gastric cancer: Current insights and future perspectives. World J Gastroenterol. 2018;24(30):3313–29.Marrelli D, Pinto E, De Stefano A, Farnetani M, Garosi L, Roviello F. Clinical utility of CEA, CA 19-9, and CA 72-4 in the follow-up of patients with resectable gastric cancer. Am J Surg. 2001;181(1):16–9.You W, Cai Z, Sheng N, Yan L, Wan H, Wang Y, et al. Construction and Validation of Convenient Clinicopathologic Signatures for Predicting the Prognosis of Stage I-III Gastric Cancer. Front Oncol. 2022;12(March):1–9.Zhou C, Zhong X, Song Y, Shi J, Wu Z, Guo Z, et al. Prognostic Biomarkers for Gastric Cancer: An Umbrella Review of the Evidence. Front Oncol. 2019;9(November):1–16.Hao NB, He YF, Li XQ, Wang K, Wang RL. The role of miRNA and lncRNA in gastric cancer. Oncotarget. 2017;8(46):81572–82.Bass AJ, Thorsson V, Shmulevich I, Reynolds SM, Miller M, Bernard B, et al. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9.Oliveira C, Suriano G, Ferreira P, Canedo P, Kaurah P, Mateus R, et al. Genetic screening for familial gastric cancer. Hered Cancer Clin Pract. 2004;2(2):51–64.Yao Y, Dai W. Genomic Instability and Cancer. J Carcinog Mutagen. 2014;5:1–17.Baj J, Brzozowska K, Forma A, Maani A, Sitarz E, Portincasa P. Immunological aspects of the tumor microenvironment and epithelial-mesenchymal transition in gastric carcinogenesis. Int J Mol Sci. 2020;21(7).Herbert A. ADAR and Immune Silencing in Cancer. Trends in Cancer. 2019;5(5):272–82.Ignatova E, Seriak D, Fedyanin M, Tryakin A, Pokataev I. Epstein – Barr virus-associated gastric cancer : disease that requires special approach. Gastric Cancer. 2020;(0123456789).Tsugane S, Sasazuki S. Diet and the risk of gastric cancer: Review of epidemiological evidence. Gastric Cancer. 2007;10(2):75–83.Rawla P, Barsouk A. Epidemiology of gastric cancer: Global trends, risk factors and prevention. Prz Gastroenterol. 2019;14(1):26–38.Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, et al. Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 2012;91(3):1071–121.Giraldo NA, Sanchez-Salas R, Peske JD, Vano Y, Becht E, Petitprez F, et al. The clinical role of the TME in solid cancer. Br J Cancer. 2019;120(1):45–53.Rezalotfi A, Ahmadian E, Aazami H, Solgi G, Ebrahimi M. Gastric cancer stem cells effect on Th17/Treg balance. A bench to beside perspective. Front Oncol. 2019;9(4):1–13.Blidner AG, Méndez-Huergo SP, Cagnoni AJ, Rabinovich GA. Re-wiring regulatory cell networks in immunity by galectin-glycan interactions. FEBS Lett. 2015;589(22):3407–18.Chang CH, Qiu J, O’Sullivan D, Buck MD, Noguchi T, Curtis JD, et al. Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression. Cell. 2015;162(6):1229–41.Vigneron N. Human Tumor Antigens and Cancer Immunotherapy. Biomed Res Int. 2015;2015:1–17.Hanahan D, Coussens LM. Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment. Cancer Cell. 2012;21(3):309–22.Maitra A. Pancreatic cancer hidden in plain sight. Nature. 2020 May 1;581(7806):34–5.Dudley AC. Tumor endothelial cells. Cold Spring Harb Perspect Med. 2012;2(3):1–18.Liu Y, Wu J, Huang W, Weng S, Wang B, Chen Y, et al. Development and validation of a hypoxia-immune-based microenvironment gene signature for risk stratification in gastric cancer. J Transl Med. 2020;18(1):1–17.Macedo F, Ladeira K, Longatto-Filho A, Martins SF. Gastric cancer and angiogenesis: Is VEGF a useful biomarker to assess progression and remission? J Gastric Cancer. 2017;17(1):1–10.Deng B, Zhu JM, Wang Y, Liu TT, Ding YB, Xiao WM, et al. Intratumor Hypoxia Promotes Immune Tolerance by Inducing Regulatory T Cells via TGF-β1 in Gastric Cancer. PLoS One. 2013;8(5):1–9.Kheshtchin N, Arab S, Ajami M, Mirzaei R, Ashourpour M, Mousavi N, et al. Inhibition of HIF-1α enhances anti-tumor effects of dendritic cell-based vaccination in a mouse model of breast cancer. Cancer Immunol Immunother. 2016;65(10):1159–67.Certo M, Tsai C-H, Pucino V, Ho P-C, Mauro C. Lactate modulation of immune responses in inflammatory versus tumour microenvironments. Nat Rev Immunol. 2020;1–11.Wang Q, Zhu D. The prognostic value of systemic immune-inflammation index (SII) in patients after radical operation for carcinoma of stomach in gastric cancer. J Gastrointest Oncol. 2019;10(5):965–78Sun X, Wang J, Liu J, Chen S, Liu X. Albumin concentrations plus neutrophil lymphocyte ratios for predicting overall survival after curative resection for gastric cancer. Onco Targets Ther. 2016 Jul 27;9:4661–9.Yang L, Liu Q, Zhang X, Liu X, Zhou B, Chen J, et al. DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature. 2020;(July 2019):1–25.Dunn GP, Bruce AT, Ikeda H, Lloyd OJ, Schreiber RD. Cancer Immunoediting: From Inmuno-Surveillance to Tumor Escape. Nat Immunol. 2002;3(11):85–99.Mohri Y, Tanaka K, Ohi M, Yokoe T, Miki C, Kusunoki M. Prognostic significance of host- and tumor-related factors in patients with gastric cancer. World J Surg. 2010;34(2):285–90.Lian L, Xia YY, Zhou C, Shen XM, Li XL, Han SG, et al. Application of platelet/lymphocyte and neutrophil/lymphocyte ratios in early diagnosis and prognostic prediction in patients with resectable gastric cancer. Cancer Biomarkers. 2015 Nov 24;15(6):899–907.Kim EY, Lee JW, Yoo HM, Park CH, Song KY. The Platelet-to-Lymphocyte Ratio Versus Neutrophil-to-Lymphocyte Ratio: Which is Better as a Prognostic Factor in Gastric Cancer? Ann Surg Oncol. 2015 Dec 1;22(13):4363–70.Kim JH, Han DS, Bang HY, Kim PS, Lee KY. Preoperative neutrophil-to-lymphocyte ratio is a prognostic factor for overall survival in patients with gastric cancer. Ann Surg Treat Res. 2015 Aug 1;89(2):81–6.Roychoudhuri R, Eil RL, Restifo NP. The interplay of effector and regulatory T cells in cancer. Curr Opin Immunol. 2015;33:101–11.Whiteside TL. The tumor microenvironment and its role in promoting tumor growth. Oncogene. 2008;27(45):5904–12.Li Q, Peng K, Chen E, Jiang H, Wang Y, Yu S, et al. IntegrinB5 upregulated by HER2 in gastric cancer: a promising biomarker for liver metastasis. Ann Transl Med. 2020;8(7):451–451.Desnoyers A, González C, Pérez-Segura P, Pandiella A, Amir E, Ocaña A. Integrin ανβ6 Protein Expression and Prognosis in Solid Tumors: A Meta-Analysis. Vol. 24, Molecular Diagnosis and Therapy. Adis; 2020. p. 143–51.Cheng S, Li X, Yuan Y, Jia C, Chen L, Gao Q, et al. ITGB1 Enhances the Proliferation, Survival, and Motility in Gastric Cancer Cells. Microsc Microanal. 2021;27(5):1192–201.Freitas D, Campos D, Gomes J, Pinto F, Macedo JA, Matos R, et al. O-glycans truncation modulates gastric cancer cell signaling and transcription leading to a more aggressive phenotype. EBioMedicine. 2019;40:349–62.LIS H, SHARON N. Protein glycosylation: Structural and functional aspects. Eur J Biochem. 1993;218(1):1–27.Wang S, Wu T, Lee C, Yu J. Dissecting the conformation of glycans and their interactions with proteins. J Biomed Sci. 2020;27(93):1–16.Harvey DJ. Proteomic analysis of glycosylation: Structural determination of N- and O-linked glycans by mass spectrometry. Expert Rev Proteomics. 2005 Feb;2(1):87–101.Fernandes E, Sores J, Cotton S, Peixoto A, Ferreira D, Freitas R, et al. Esophageal, gastric and colorectal cancers: Looking beyond classical serological biomarkers towards glycoproteomics-assisted precision oncology. Theranostics. 2020;10(11):4903–28.Reindl J, Shevtsov M, Dollinger G, Stangl S, Multhoff G. Membrane Hsp70-supported cell-to-cell connections via tunneling nanotubes revealed by live-cell STED nanoscopy. Cell Stress Chaperones. 2019;213–21.Trinchera M, Aronica A, Dall’Olio F. Selectin ligands Sialyl-Lewis a and Sialyl-Lewis x in gastrointestinal cancers. Biology (Basel). 2017;6(1):1–18.Isomoto H, Oka M, Yano Y, Kanazawa Y, Soda H, Terada R, et al. Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer. Cancer Lett. 2003;198(2):219–28.Berezowska S, Novotny A, Bauer K, Feuchtinger A, Slotta-Huspenina J, Becker K, et al. Association between HSP90 and Her2 in gastric and gastroesophageal carcinomas. PLoS One. 2013;8(7):e69098.Kang GH, Lee EJ, Jang KT, Kim K-M, Park CK, Lee C-S, et al. Expression of HSP90 in gastrointestinal stromal tumours and mesenchymal tumours. Histopathology. 2010 May;56(6):694–701.Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005;10(2):86–103.Wang J, Cui S, Zhang X, Wu Y, Tang H. High Expression of Heat Shock Protein 90 Is Associated with Tumor Aggressiveness and Poor Prognosis in Patients with Advanced Gastric Cancer. PLoS One. 2013;8(4).Chung YM, Park S, Park JK, Kim Y, Kang Y, Yoo YD. Establishment and characterization of 5-fluorouracil-resistant gastric cancer cells. Cancer Lett. 2000;159(1):95–101.Pfister K, Radons J, Busch R, Tidball JG, Pfeifer M, Freitag L, et al. Patient survival by Hsp70 membrane phenotype: Association with different routes of metastasis. Cancer. 2007;110(4):926–35.Wang FL, Cui SX, Sun LP, Qu XJ, Xie YY, Zhou L, et al. High expression of α 2, 3-linked sialic acid residues is associated with the metastatic potential of human gastric cancer. Cancer Epidemiol. 2009;32(5–6):437–43.Sun X, Li D, Duan Z. Structural Basis of Glycan Recognition of Rotavirus. Front Mol Biosci. 2021;8(July):1–12.Bertuzzi S, Quintana JI, Ardá A, Gimeno A, Jiménez-Barbero J. Targeting Galectins With Glycomimetics. Front Chem. 2020;8(593):1–17.Liu Y, Meng H, Xu S, Qi X. Galectins for Diagnosis and Prognostic Assessment of Human Diseases: An Overview of Meta-Analyses. Med Sci Monit. 2020;26:e923901.Wolf Y, Anderson AC, Kuchroo VK. TIM3 comes of age as an inhibitory receptor. Nat Rev Immunol. 2020;20(3):173–85.Bacigalupo ML, Carabias P, Troncoso MF. Contribution of galectin-1, a glycan-binding protein, to gastrointestinal tumor progression. World J Gastroenterol. 2017;23(29):5266–81.Long B, Yu Z, Zhou H, Ma Z, Ren Y, Zhan H, et al. Clinical characteristics and prognostic significance of galectins for patients with gastric cancer: A meta-analysis. Int J Surg. 2018;56(82):242–9.Zhai E, Liang W, Lin Y, Huang L, He X, Cai S, et al. HSP70/HSP90-Organizing Protein Contributes to Gastric Cancer Progression in an Autocrine Fashion and Predicts Poor Survival in Gastric Cancer. Cell Physiol Biochem. 2018;47(2):879–92.Datta D, Banerjee S, Ghosh A, Mustafi SB, Raha S. Involvement of Heat Shock Protein 70 (Hsp70) in Gastrointestinal Cancers. In: HSP70 in Human Diseases and Disorders. Springer Nature; 2018. p. 71–91.Isomoto H, Oka M, Yano Y, Kanazawa Y, Soda H, Terada R, et al. Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer. Cancer Lett. 2003 Aug 1;198(2):219–28.Ge H, Yan Y, Lingfei G, Fei T, Di W. Prognostic role of hsPs in human gastrointestinal cancer: a systematic review and meta-analysis. Onco Targets Ther. 2018;11(28):351–9.Hoter A, El-Sabban ME, Naim HY. The HSP90 family: Structure, regulation, function, and implications in health and disease. Int J Mol Sci. 2018;19(9).HW L, KM K. Clinical Significance of Heat Shock Protein 90α Expression as a Biomarker of Prognosis in Patients With Gastric Cancer. Niger J Clin Pract. 2019;22(12):1699–705.Zhang L, Hou Y, Li N, Wu K, Zhai J. The influence of TXNDC5 gene on gastric cancer cell. J Cancer Res Clin Oncol. 2010;136(10):1497–505.Wu J, Chen X, Wang X, Yu Y, Ren J, Xiao Y. ERp19 contributes to tumorigenicity in human gastric cancer by promoting cell growth , migration and invasion. 2015;6(14).Leys CM, Nomura S, LaFleur BJ, Ferrone S, Kaminishi M, Montgomery E, et al. Expression and prognostic significance of prothymosin-α and ERp57 in human gastric cancer. Surgery. 2007;141(1):41–50.Liu T, Liu D, Kong X, Dong M. Clinicopathological Significance of Heat Shock Protein (HSP) 27 Expression in Gastric Cancer: A Updated Meta-Analysis. Evidence-based Complement Altern Med. 2020;2020.Song D, Guo M, Wu K, Hao J, Nie Y, Fan D. Silencing of ER-resident oxidoreductase PDIA3 inhibits malignant biological behaviors of multidrug-resistant gastric cancer. Acta Biochim Biophys Sin (Shanghai). 2021;53(9):1216–26.Zhang D, Fan D. New insights into the mechanisms of gastric cancer multidrug resistance and future perspectives. Futur Oncol. 2010;6(4):527–37.Arienti C, Pignatta S, Tesei A. Epidermal Growth Factor Receptor Family and its Role in Gastric Cancer. Front Oncol. 2019;9(November):1–11.Zhang D, Fan D. Multidrug resistance in gastric cancer: recent research advances and ongoing therapeutic challenges. Expert Rev Anticancer Ther. 2007 Oct;7(10):1369–78.Gambardella V, Castillo J, Tarazona N, Gimeno-Valiente F, Martínez-Ciarpaglini C, Cabeza M, et al. The role of Tumor-Associated Macrophages in Gastric Cancer development and their potential as a therapeutic target. Cancer Treat Rev. 2020;86(March):102015.He X-J, Tao H-Q, Hu Z-M, Ma Y-Y, Xu J, Wang H-J, et al. Expression of galectin-1 in carcinoma-associated fibroblasts promotes gastric cancer cell invasion through upregulation of integrin β1. Cancer Sci. 2014;105(11):1402–10.Shao D, Wang X, Li Z, Xing X, Cheng X, Guo T, et al. High-level SAE2 promotes malignant phenotype and predicts outcome in gastric cancer. Am J Cancer Res. 2015;5(2):589–602.Herrmann K, Walch a, Balluff B, Tanzer M, Hofler H, Krause BJ, et al. Proteomic and metabolic prediction of response to therapy in gastrointestinal cancers. Nat Clin Pr Gastroenterol Hepatol. 2009;6(3):170–83.Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): A double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct 1;15(11):1224–35.Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, et al. Everolimus for previously treated advanced gastric cancer: Results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol. 2013;31(31):3935–43.Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 3;383(9911):31–9.Yang L, Wang Y, Wang H. Use of immunotherapy in the treatment of gastric cancer (Review). Oncol Lett. 2019;18(6):5681–90.Giampieri R, Maccaroni E, Mandolesi A, Del Prete M, Andrikou K, Faloppi L, et al. Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy. Gastric Cancer. 2017;20(1):156–63.Kang YK, Rha SY, Tassone P, Barriuso J, Yu R, Szado T, et al. A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. Br J Cancer. 2014;111(4):660–6.Nie S, Yang G, Lu H. Current molecular targeted agents for advanced gastric cancer. Onco Targets Ther. 2020;13:4075–88.Motoshima S, Yonemoto K, Kamei H, Morita M, Yamaguchi R. Prognostic implications of HER2 heterogeneity in gastric cancer. Oncotarget. 2018;9(10):9262–72.Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, et al. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct 1;19(10):1372–84.DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01] - Full Text View - ClinicalTrials.gov [Internet]. [cited 2020 Jun 17]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03329690Han HS, Kim BJ, Jee H-J, Ryu M-H, Park SH, Rha SY, et al. Ramucirumab plus paclitaxel as second-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma: a nationwide real-world outcomes in Korea study (KCSG-ST19-16). Ther Adv Med Oncol. 2021;13:17588359211042812.Li X, Zhu X, Wang Y, Wang R, Wang L, Zhu ML, et al. Prognostic value and association of lauren classification with vegf and vegfr-2 expression in gastric cancer. Oncol Lett. 2019;18(5):4891–9.O’Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2019;16(3):151–67.Petitprez F, Meylan M, de Reyniès A, Sautès-Fridman C, Fridman WH. The Tumor Microenvironment in the Response to Immune Checkpoint Blockade Therapies. Front Immunol. 2020;11(May):1–11.Chen LT, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, et al. A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data. Gastric Cancer. 2020;23(3):510–9.Xiang Z, Chen W, Zhang J, Song S, Xia GK, Huang XY, et al. Identification of discrepancy between CTLA4 expression and CTLA4 activation in gastric cancer. Immunopharmacol Immunotoxicol. 2019;41(3):386–93.Gu L, Chen M, Guo D, Zhu H, Zhang W, Pan J, et al. PD-L1 and gastric cancer prognosis: A systematic review and meta-analysis. PLoS One. 2017;12(8):1–14.Picardo SL, Doi J, Hansen AR. Structure and optimization of checkpoint inhibitors. Cancers (Basel). 2020;12(1):1–15.Kulangara K, Hanks DA. Development of the combined positive score (CPS) for the evaluation of PD-L1 in solid tumors with the immunohistochemistry assay PD-L1 IHC 22C3 pharmDx. J Clin Oncol. 2017;25(15).Bang YJ, Kang YK, Catenacci D V., Muro K, Fuchs CS, Geva R, et al. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer. 2019;22(4):828–37.Mendis S, Gill S. Cautious optimism-the current role of immunotherapy in gastrointestinal cancers. Curr Oncol. 2020;27(April):S59–68.Iwasa S, Kudo T, Takahari D, Hara H, Kato K, Satoh T. Practical guidance for the evaluation of disease progression and the decision to change treatment in patients with advanced gastric cancer receiving chemotherapy. Int J Clin Oncol. 2020;(Table 1).Waddell T, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D. Gastric cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Eur J Surg Oncol. 2014;40(5):584–91.Cao GD, He XB, Sun Q, Chen S, Wan K, Xu X, et al. The Oncolytic Virus in Cancer Diagnosis and Treatment. Front Oncol. 2020;10(September):1–12.Jayawardena N, Poirier JT, Burga LN, Bostina M. Virus–Receptor Interactions and Virus Neutralization: Insights for Oncolytic Virus Development. Oncolytic Virotherapy. 2020;Volume 9:1–15.Achard C, Surendran A, Wedge ME, Ungerechts G, Bell J, Ilkow CS. Lighting a Fire in the Tumor Microenvironment Using Oncolytic Immunotherapy. EBioMedicine. 2018;31:17–24.Noonan AM, Farren MR, Geyer SM, Huang Y, Tahiri S, Ahn D, et al. Randomized Phase 2 Trial of the Oncolytic Virus Pelareorep (Reolysin) in Upfront Treatment of Metastatic Pancreatic Adenocarcinoma. Mol Ther. 2016;24(6):1150–8.Workenhe ST, Mossman KL. Oncolytic Virotherapy and Immunogenic Cancer Cell Death: Sharpening the Sword for Improved Cancer Treatment Strategies. Mol Ther. 2013;22(2):251–6.Alvarez-Breckenridge C a, Choi BD, Suryadevara CM, Chiocca EA. Potentiating oncolytic viral therapy through an understanding of the initial immune responses to oncolytic viral infection. Curr Opin Virol. 2015;13:25–32.Guo ZS, Liu Z, Bartlett DL. Oncolytic Immunotherapy: Dying the Right Way is a Key to Eliciting Potent Antitumor Immunity. Front Oncol. 2014;4(April):1–11.Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov. 2015;14(9).Heiniö C, Havunen R, Santos J, Lint K de, Cervera-Carrascon V, Kanerva A, et al. TNFa and IL2 Encoding Oncolytic Adenovirus Activates Pathogen and Danger-Associated Immunological Signaling. Cells. 2020;9(4):1–13.Pol J, Bloy N, Obrist F, Eggermont A, Galon J, Cremer I, et al. Trial Watch:: Oncolytic viruses for cancer therapy. Oncoimmunology. 2014;3(April):e28694.Cattaneo R, Russell SJ. How to develop viruses into anticancer weapons. PLoS Pathog. 2017;13(3):8–13.Garijo R, Hernández-Alonso P, Rivas C, Diallo JS, Sanjuán R. Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells. PLoS One. 2014;9(7):1–8.Kaufman HL, Bommareddy PK. Two roads for oncolytic immunotherapy development. J Immunother Cancer. 2019;7(1):1–5.Alberts P, Tilgase A, Rasa A, Bandere K, Venskus D. The advent of oncolytic virotherapy in oncology: The Rigvir® story. Eur J Pharmacol. 2018;837(August):117–26.Liang M. Oncorine, the World First Oncolytic Virus Medicine and its Update in China. Curr Cancer Drug Targets. 2018;18(2):171–6.Sugawara K, Iwai M, Yajima S, Tanaka M, Yanagihara K, Seto Y, et al. Efficacy of a Third-Generation Oncolytic Herpes Virus G47Δ in Advanced Stage Models of Human Gastric Cancer. Mol Ther oncolytics. 2020 Jun;17:205–15.Medicine USNL of. https://clinicaltrials.gov [Internet]. 2022 [cited 2022 Jun 5]. Available from: https://clinicaltrials.govGao P, Ding G, Wang L. The efficacy and safety of oncolytic viruses in the treatment of intermediate to advanced solid tumors: A systematic review and meta-analysis. Transa Cancer Res. 2021;10(10):4290–302.Coffin RS. From virotherapy to oncolytic immunotherapy: where are we now? Curr Opin Virol. 2015;13:93–100.Diccionario de cáncer del NCI - Instituto Nacional del Cáncer [Internet]. [cited 2020 Oct 17]. Available from: https://www.cancer.gov/espanol/publicaciones/diccionario/def/efecto-abscopalBishop RF, Davidson GP, Holmes IH, Ruck BJ. Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis. Lancet (London, England). 1973 Dec 8;2(7841):1281–3.Desselberger U. Rotaviruses. Virus Res. 2014;190:75–96.Hoshino Y, Sereno MM, Midthun K, Flores J, Kapikian AZ, Chanock RM. Independent segregation of two antigenic specificities (VP3 and VP7) involved in neutralization of rotavirus infectivity. Proc Natl Acad Sci U S A. 1985;82(24):8701–4.Thomas RJ, Bartee E. The use of oncolytic virotherapy in the neoadjuvant setting. J Immunother Cancer. 2022;10:1–9.Hoxie I, Dennehy JJ. Intragenic recombination influences rotavirus diversity and evolution. Virus Evol. 2020;6(1):1–16.Crawford SE, Ramani S, Tate JE, Parashar UD, Svensson L, Hagbom M, et al. Rotavirus infection. Nat Rev Dis Prim. 2017;3(17083):1–16.Flewett T, Bryden A, Davies H. VIRUS PARTICLES IN EPITHELIAL CELLS OF DUODENAL MUCOSA FROM CHILDREN WITH ACUTE NON-BACTERIAL GASTROENTERITIS. Lancet. 1973;302(7844):1497.Amimo JO, Raev SA, Chepngeno J, Mainga AO, Guo Y, Saif L, et al. Rotavirus Interactions With Host Intestinal Epithelial Cells. Front Immunol. 2021;12(December):1–17.Pesavento JB, Crawford SE, Estes MK, Prasad BVV. Rotavirus proteins: structure and assembly. Curr Top Microbiol Immunol. 2006;309:189–219.Kumar D, Yu X, Crawford SE, Moreno R, Jakana J, Sankaran B, et al. 2.7 Å cryo-EM structure of rotavirus core protein VP3, a unique capping machine with a helicase activity. Sci Adv. 2020;6(16):1–10.Feng N, Hu L, Ding S, Sanyal M, Zhao B, Sankaran B, et al. Human VP8* mAbs neutralize rotavirus selectively in human intestinal epithelial cells. J Clin Invest. 2019 Aug 13;129(9).Arias CF, Silva-Ayala D, López S. Rotavirus Entry: a Deep Journey into the Cell with Several Exits. J Virol. 2015;89(November):890–3.Trask SD, Ogden KM, Patton JT. Interactions among capsid proteins orchestrate rotavirus particle functions. Curr Opin Virol. 2012;2(4):373–9.Aoki ST, Settembre E, Trask SD, Greenberg HB, Stephen C, Dormitzer PR. Structure of rotavirus outer-layer protein VP7 bound with a neutralizing Fab. Science (80- ). 2009;324(5933):1444–7.King AMQ, Adams MJ, Lefkowitz EJ. Virus Taxonomy: Classification and Nomenclature of Viruses : Ninth Report of the International Committee on Taxonomy of Viruses. Elsevier; 2011. 1327 p.Gautam R, Esona MD, Mijatovic-Rustempasic S, Ian Tam K, Gentsch JR, Bowen MD. Real-time RT-PCR assays to differentiate wild-type group A rotavirus strains from Rotarix(®) and RotaTeq(®) vaccine strains in stool samples. Hum Vaccin Immunother. 2013;10(3):767–77.Gualtero DF, Guzmán F, Acosta O, Guerrero C a. Amino acid domains 280-297 of VP6 and 531-554 of VP4 are implicated in heat shock cognate protein hsc70-mediated rotavirus infection. Arch Virol. 2007;152:2183–96.Suzuki H. Rotavirus replication: Gaps of knowledge on virus entry and morphogenesis. Tohoku J Exp Med. 2019;248(4):285–96.Maruri-Avidal L, López S, Arias CF. Endoplasmic reticulum chaperones are involved in the morphogenesis of rotavirus infectious particles. J Virol. 2008;82(11):5368–80.Coulson BS, Londrigan SL, Lee DJ. Rotavirus contains integrin ligand sequences and a disintegrin-like domain that are implicated in virus entry into cells. Proc Natl Acad Sci U S A. 1997;94(10):5389–94.Guerrero C, Méndez E, Zárate S, Isa P, López S, Arias CF. Integrin alpha(v)beta(3) mediates rotavirus cell entry. Proc Natl Acad Sci U S A. 2000;97(26):14644–9.Zárate S, Espinosa R, Romero P, Guerrero CA, Arias CF, López S. Integrin alpha2beta1 mediates the cell attachment of the rotavirus neuraminidase-resistant variant nar3. Virology. 2000;278(1):50–4.Graham KL, Halasz P, Tan Y, Hewish MJ, Takada Y, Mackow ER, et al. Integrin-using rotaviruses bind alpha2beta1 integrin alpha2 I domain via VP4 DGE sequence and recognize alphaXbeta2 and alphaVbeta3 by using VP7 during cell entry. J Virol. 2003;77(18):9969–78.Zárate S, Romero P, Espinosa R, Arias CF, López S. VP7 Mediates the Interaction of Rotaviruses with Integrin αvβ3 through a Novel Integrin-Binding Site. J Virol. 2004;78(20):10839–47.Guerrero CA, Santana AY, Acosta O. Mouse intestinal villi as a model system for studies of rotavirus infection. J Virol Methods. 2010;168(1–2):22–30.Arias CF, Isa P, Guerrero C a, Méndez E, Zárate S, López T, et al. Molecular biology of rotavirus cell entry. Arch Med Res. 2002;33(4):356–61Pérez-Ortín R, Vila-Vicent S, Carmona-Vicente N, Santiso-Bellón C, Rodríguez-Díaz J, Buesa J. Histo-blood group antigens in children with symptomatic rotavirus infection. Viruses. 2019;11(4).Acosta O, Calderon M, Moreno L, Guerrero C a. UN MODELO DEL MECANISMO DE ENTRADA DE LOS ROTAVIRUS A LA CÉLULA HOSPEDERA. Rev Fac Med Univ Nac Colomb. 2009;57(2):124–48.Desselberger U, Richards J, Tchertanov L, Lepault J, Lever A, Burrone O, et al. Further characterisation of rotavirus cores: Ss(+)RNAs can be packaged in vitro but packaging lacks sequence specificity. Virus Res. 2013;178(2):252–63.Chen D, Ramig RF. Rescue of infectivity by sequential in vitro transcapsidation of rotavirus core particles with inner capsid and outer capsid proteins. Virology. 1993 Jun;194(2):743–51.Yoder JD, Trask SD, Vo PT, Binka M, Feng N, Harrison SC, et al. VP5* Rearranges when Rotavirus Uncoats. J Virol. 2009;83(21):11372–7.Fleming FE, Bohm R, Dang VT, Holloway G, Haselhorst T, Madge PD, et al. Relative Roles of GM1 Ganglioside, N-Acylneuraminic Acids, and 2 1 Integrin in Mediating Rotavirus Infection. J Virol. 2014;88(8):4558–71.Ciarlet M, Ludert JE, Iturriza-Gómara M, Liprandi F, Gray JJ, Desselberger U, et al. Initial interaction of rotavirus strains with N-acetylneuraminic (sialic) acid residues on the cell surface correlates with VP4 genotype, not species of origin. J Virol. 2002;76(8):4087–95.Guo LA, Zhang M, Hou Y zhen, Hu H, Fang L, Tan M, et al. Epidemiology and HBGA-susceptibility investigation of a G9P[8] rotavirus outbreak in a school in Lechang, China. Arch Virol. 2020;165(6):1311–20.Coulson BS. Expanding diversity of glycan receptor usage by rotaviruses. Curr Opin Virol. 2015 Dec;15:90–6.Delorme C, Brüssow H, Teneberg S. Glycosphingolipid Binding Specificities of Rotavirus: Identification of a Sialic Acid-Binding Epitope ´. J Microbiol. 2001;75(5):2276–87.Kun HR, Strains MO. Ganglioside GMi a on the Cell Surface Is Involved in the Infection by. 1999;688:683–8.Pérez-Vargas J, Romero P, López S, Arias CF. The peptide-binding and ATPase domains of recombinant hsc70 are required to interact with rotavirus and reduce its infectivity. J Virol. 2006;80(7):3322–31.Zárate S, Cuadras M a, Espinosa R, Romero P, Juárez KO, Camacho-Nuez M, et al. Interaction of rotaviruses with Hsc70 during cell entry is mediated by VP5. J Virol. 2003;77(13):7254–60.Fleming FE, Graham KL, Takada Y, Coulson BS. Determinants of the specificity of rotavirus interactions with the alpha2beta1 integrin. J Biol Chem. 2011 Feb 25;286(8):6165–74.Santana AY, Guerrero C a., Acosta O. Implication of Hsc70, PDI and integrin avb3 involvement during entry of the murine rotavirus ECwt into small-intestinal villi of suckling mice. Arch Virol. 2013;158(6):1323–36.Torres-Flores JM, Silva-Ayala D, Espinoza M a., López S, Arias CF. The tight junction protein JAM-A functions as coreceptor for rotavirus entry into MA104 cells. Virology. 2015;475:172–8.Patton JT, Hua J, Mansell EA. Location of intrachain disulfide bonds in the VP5* and VP8* trypsin cleavage fragments of the rhesus rotavirus spike protein VP4. J Virol. 1993;67(8):4848–55.Calderón MN, Guerrero C a, Acosta O, Lopez S, Arias CF. Inhibiting Rotavirus Infection by Membrane- Impermeant Thiol / Disulfide Exchange Blockers and Antibodies against Protein Disulfide. Intervirology. 2012;55(3):451–64.Calderón MN, Guerrero C a, Domínguez Y, Garzón E, Barreto SM, Acosta O. Interaction of rotavirus with protein disulfide isomerase in vitro and cell system [Interacción de rotavirus con la proteína disulfuro-isomerasa in vitro y en sistemas celulares]. Biomedica. 2011;31(1):70–81.Settembre EC, Chen JZ, Dormitzer PR, Grigorieff N, Harrison SC. Atomic model of an infectious rotavirus particle. EMBO J. 2011;30(2):408–16.Dormitzer PR, Sun ZYJ, Wagner G, Harrison SC. The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site. EMBO J. 2002;21(5):885–97.Trask SD, McDonald SM, Patton JT. Structural Insights into the Coupling of Virion Assembly and Rotavirus Replication. Nat Rev Microbiol. 2013;10(3):165–77.Silva-Ayala D, López T, Gutiérrez M, Perrimon N, López S, Arias CF. Genome-wide RNAi screen reveals a role for the ESCRT complex in rotavirus cell entry. Proc Natl Acad Sci U S A. 2013;110(25):10270–5.Santoro MG, Amici C, Rossi A. Role of Heat Shock Proteins in Viral Infection. In: Pockley A., Calderwood S. SM, editor. Prokaryotic and Eukaryotic Heat Shock Proteins in Infectious Disease Heat Shock Proteins. 4th ed. Springer; 2009. p. 51–84.Ogden KM, Snyder MJ, Dennis AF, Patton JT. Predicted Structure and Domain Organization of Rotavirus Capping Enzyme and Innate Immune Antagonist VP3. J Virol. 2014;88(16):9072–85.Piron M, Vende P, Cohen J, Poncet D. Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A) binding protein from eIF4F. EMBO J. 1998;17(19):5811–21.Vende P, Piron M, Castagné N, Poncet D. Efficient Translation of Rotavirus mRNA Requires Simultaneous Interaction of NSP3 with the Eukaryotic Translation Initiation Factor eIF4G and the mRNA 3′ End. J Virol. 2000;74(15):7064–71.Arnold MM. The Rotavirus Interferon Antagonist NSP1: Many Targets, Many Questions. J Virol. 2016;90(11):5212–5.Gratia M, Sarot E, Vende P, Charpilienne A, Baron CH, Duarte M, et al. Rotavirus NSP3 Is a Translational Surrogate of the Poly(A) Binding Protein-Poly(A) Complex. J Virol. 2015 Sep 1;89(17):8773–82.Glück S, Buttafuoco A, Meier AF, Arnoldi F, Vogt B, Schraner EM, et al. Rotavirus replication is correlated with S/G2 interphase arrest of the host cell cycle. PLoS One. 2017;12(6):1–24.Ball JM, Mitchell DM, Gibbons TF, Parr RD. Review Rotavirus NSP4: A Multifunctional Viral Enterotoxin. VIRAL Immunol. 2005;18(1):27–40.Eichwald C, Arnoldi F, Laimbacher AS, Schraner EM, Fraefel C, Wild P, et al. Rotavirus viroplasm fusion and perinuclear localization are dynamic processes requiring stabilized microtubules. PLoS One. 2012;7(10):e47947.Suárez YG, Martínez JL, Hernández DT, Hernández HO, Pérez-Delgado A, Méndez M, et al. Nanoscale organization of rotavirus replication machineries. Elife. 2019;8:1–53.Crawford SE, Desselberger U. Lipid droplets form complexes with viroplasms and are crucial for rotavirus replication. Curr Opin Virol. 2016;19:11–5.López T, Camacho M, Zayas M, Nájera R, Sánchez R, Arias CF, et al. Silencing the Morphogenesis of Rotavirus. J Virol. 2005;79(1):184–92.Carreño-Torres JJ, Gutiérrez M, Arias CF, López S, Isa P. Characterization of viroplasm formation during the early stages of rotavirus infection. Virol J. 2010;7(1):350.Viskovska M, Anish R, Hu L, Chow D-C, Hurwitz AM, Brown NG, et al. Probing the sites of interactions of rotaviral proteins involved in replication. J Virol. 2014;88(21):12866–81.Bennett J, Dolin R, Blaser M. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Elsevier Inc; 2015. 1857–1858 p.Qin L, Ren L, Zhou Z, Lei X, Chen L, Xue Q, et al. Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I. Virol J. 2011;8:526.Davis CA, Morelli KA, Patton MT. Rotavirus NSP1 Requires Casein Kinase II-Mediated Phosphorylation for Hijacking of Cullin-RING Ligases. MBio. 2017;8(4):1213–30.Sastri NP, Viskovska M, Hyser JM, Tanner MR, Horton LB, Sankaran B, et al. Structural Plasticity of the Coiled-Coil Domain of Rotavirus NSP4. J Virol. 2014;88(23):13602–12.Crawford SE, Criglar JM, Liu Z, Broughman JR, Estes MK. COPII Vesicle Transport Is Required for Rotavirus NSP4 Interaction with the Autophagy Protein LC3 II and Trafficking to Viroplasms. J Virol. 2019;94(1):1–14.Razavinikoo H, Soleimanjahi H, Haqshenas G, Bamdad T, Goodarzi Z. Activation of calcium / calmodulin-dependent kinase following bovine rotavirus enterotoxin NSP4 expression. Iran J Basic Med Sci. 2015;18(4):2–6.Seo N-S, Zeng CQ-Y, Hyser JM, Utama B, Crawford SE, Kim KJ, et al. Integrins alpha1beta1 and alpha2beta1 are receptors for the rotavirus enterotoxin. Proc Natl Acad Sci U S A. 2008;105(26):8811–8.Hu L, Crawford SE, Hyser JM, Estes MK, Prasad BVVV. Rotavirus non-structural proteins : Structure and Function. Curr Opin Virol. 2012;2(4):380–8.Rivera M, Guerrero CA, Acosta O. Thiol/disulfide exchange occurs in rotavirus structural proteins during contact with intestinal villus cell surface. Acta Virol. 2020;64(1):44–58.Rico J, Perez C, Hernandez J, Guerrero C, Acosta O. Cell surface heat shock protein-mediated entry of tumor cell-adapted rotavirus into U-937 cells. Folia Microbiol (Praha). 2021;(0123456789).Rico J, Perez C, Guerrero R, Hernandez J, Guerrero C, Acosta O. Implication of heat shock proteins in rotavirus entry into Reh cells. Acta Virol. 2020;64(4):433–50.Perez C, Rico J, Guerrero C, Acosta O. Role of heat-shock proteins in infection of human adenocarcinoma cell line MCF-7 by tumor-adapted rotavirus isolates. Colomb medica (Cali, Colomb. 2021;52(1):e2024196.Guerrero R, Guerrero C, Acosta O. Induction of cell death in the human acute lymphoblastic leukemia cell line reh by infection with rotavirus isolate Wt1-5. Vol. 8, Biomedicines. 2020. 1–33 p.Liou GY, Storz P. Reactive oxygen species in cancer. Vol. 44, Free Radical Research. 2010.Yang H, Villani RM, Wang H, Simpson MJ, Roberts MS, Tang M, et al. The role of cellular reactive oxygen species in cancer chemotherapy. Vol. 37, Journal of Experimental and Clinical Cancer Research. 2018.Guerrero CA, Bouyssounade D, Zárate S, Iša P, López T, Espinosa R, et al. Heat Shock Cognate Protein 70 Is Involved in Rotavirus Cell Entry. J Virol. 2002;76(8):4096–102.Arias CF, López S. Rotavirus cell entry: not so simple after all. Curr Opin Virol. 2021;48:42–8.Abdelhakim AH, Salgado EN, Fu X, Pasham M, Nicastro D, Kirchhausen T, et al. Structural Correlates of Rotavirus Cell Entry. PLoS Pathog. 2014;10(9):e1004355.Jiang Y, Zhang Q, Hu Y, Li T, Yu J, Zhao L, et al. ImmunoScore Signature: A Prognostic and Predictive Tool in Gastric Cancer. Ann Surg. 2018;267(3):504–13.Song Z, Wu Y, Yang J, Yang D, Fang X. Progress in the treatment of advanced gastric cancer. Tumor Biol. 2017;39(7).Sanjuán R, Grdzelishvili VZ. Evolution of oncolytic viruses. Curr Opin Virol. 2015;13:1–5.Hu B, El Hajj N, Sittler S, Lammert N, Barnes R, Meloni-Ehrig A. Gastric cancer: Classification, histology and application of molecular pathology. J Gastrointest Oncol. 2012;3(3):251–61.Arnold M, Patton JT, McDonald SM. Culturing, storage, and quantification of rotaviruses. Current Protocols in Microbiology. 2009. p. 1–29.Diallo JS, Roy D, Abdelbary H, de Silva N, Bell JC. Ex vivo infection of live tissue with oncolytic viruses. J Vis Exp. 2011;(52):2–6.Introini A, Vanpouille C, Fitzgerald W, Broliden K, Margolis L. Ex vivo infection of human lymphoid tissue and female genital mucosa with human immunodeficiency virus 1 and histoculture. J Vis Exp. 2018;2018(140).Varghese F, Bukhari AB, Malhotra R, De A. IHC profiler: An open source plugin for the quantitative evaluation and automated scoring of immunohistochemistry images of human tissue samples. PLoS One. 2014;9(5):1–11.Seyed Jafari SM, Hunger RE. IHC optical density score: A new practical method for quantitative immunohistochemistry image analysis. Appl Immunohistochem Mol Morphol. 2017;25(1):e12–3.Lin PH, Selinfreund R, Wakshull E, Wharton W. Rapid and Efficient Purification of Plasma Membrane from Cultured Cells: Characterization of Epidermal Growth Factor Binding. Biochemistry. 1987;26(3):731–6.Seymour LW, Fisher KD. Oncolytic viruses: finally delivering. Br J Cancer. 2016;114:357–61.López S, Arias CF. Multistep entry of rotavirus into cells: A Versaillesque dance. Trends Microbiol. 2004;12(6):271–8.Graham KL, Halasz P, Tan Y, Hewish MJ, Takada Y, Mackow ER, et al. Integrin-using rotaviruses bind alpha2beta1 integrin alpha2 I domain via VP4 DGE sequence and recognize alphaXbeta2 and alphaVbeta3 by using VP7 during cell entry. J Virol. 2003;77(18):9969–78.Vousden KH, Lu X. Live or let die: The cell’s response to p53. Nat Rev Cancer. 2002;2(8):594–604.Aubrey BJ, Kelly GL, Janic A, Herold MJ, Strasser A. How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ. 2018;25(1):104–13.Gryko M, Pryczynicz A, Zareba K, Kȩdra B, Kemona A, Guzińska-Ustymowicz K. The expression of Bcl-2 and BID in gastric cancer cells. J Immunol Res. 2014;2014:1–5.Holloway G, Coulson BS. Innate cellular responses to rotavirus infection. J Gen Virol. 2013;94(PART 6):1151–60.Hundahl SA, Phillips JL, Menck HR. The National Cancer Data Base report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy. Cancer. 2000;88(4):921–32.Izumi D, Nunobe S. How to Decide Approaches and Procedures for Early and Advanced Gastric Cancer ? Can J Gastroenterol Hepatol. 2022;2022:1–5.Fouad YA, Aanei C. Revisiting the hallmarks of cancer. Am J Cancer Res. 2017;7(5):1016–36.Breitbach CJ, Paterson JM, Lemay CG, Falls TJ, McGuire A, Parato KA, et al. Targeted inflammation during oncolytic virus therapy severely compromises tumor blood flow. Mol Ther. 2007;15(9):1686–93.Kloker L, Yurttas C, Lauer U. Three-dimensional tumor cell cultures employed in virotherapy research. Oncolytic Virotherapy. 2018;Volume 7:79–93.Breitbach CJ, De Silva NS, Falls TJ, Aladl U, Evgin L, Paterson J, et al. Targeting tumor vasculature with an oncolytic virus. Mol Ther. 2011;19(5):886–94.Kooti W, Esmaeili Gouvarchin Ghaleh H, Farzanehpour M, Dorostkar R, Jalali Kondori B, Bolandian M. Oncolytic Viruses and Cancer, Do You Know the Main Mechanism? Front Oncol. 2021;11(December):1–11.Khan HA, Mutus B. Protein disulfide isomerase a multifunctional protein with multiple physiological roles. Front Chem. 2014;2(AUG):1–9.Giaginis C, Daskalopoulou SS, Vgenopoulou S, Sfiniadakis I, Kouraklis G, Theocharis SE. Heat Shock Protein-27, -60 and -90 expression in gastric cancer: Association with clinicopathological variables and patient survival. BMC Gastroenterol. 2009;9:1–10.Geyer PE, Maak M, Nitsche U, Perl M, Novotny A, Slotta-Huspenina J, et al. Gastric adenocarcinomas express the glycosphingolipid Gb3/CD77: Targeting of gastric cancer cells with Shiga toxin B-subunit. Mol Cancer Ther. 2016;15(5):1008–17.Elmallah MIY, Cordonnier M, Vautrot V, Chanteloup G, Garrido C, Gobbo J. Membrane-anchored heat-shock protein 70 (Hsp70) in cancer. Cancer Lett. 2020;469(August 2019):134–41.Goodarzi Z, Soleimanjahi H, Arefian E, Saberfar E. The effect of bovine rotavirus and its nonstructural protein 4 on ER stress-mediated apoptosis in HeLa and HT-29 cells. Tumor Biol. 2015 Oct 1;37(3):3155–61.Zhou Y, Frey TK, Yang JJ. Viral calciomics: Interplays between Ca2+ and virus. Cell Calcium. 2009;46(1):1–17.Martin-Latil S, Mousson L, Autret A, Colbère-Garapin F, Blondel B. Bax is activated during rotavirus-induced apoptosis through the mitochondrial pathway. J Virol. 2007 May;81(9):4457–64.Mukherjee A, Patra U, Bhowmick R, Chawla-Sarkar M. Rotaviral nonstructural protein 4 triggers dynamin-related protein 1-dependent mitochondrial fragmentation during infection. Cell Microbiol. 2018 Jun;20(6):e12831Chattopadhyay S, Mukherjee A, Patra U, Bhowmick R, Basak T, Sengupta S, et al. Tyrosine phosphorylation modulates mitochondrial chaperonin Hsp60 and delays rotavirus NSP4-mediated apoptotic signaling in host cells. Cell Microbiol. 2017 Mar;19(3).Vojtěšek B, Bártek J, Midgley CA, Lane DP. An immunochemical analysis of the human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods. 1992;151(1–2).Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene. 2003;22(56 REV. ISS. 8):9030–40.Bhowmick R, Halder UC, Chattopadhyay S, Nayak MK, Chawla-Sarkar M. Rotavirus-Encoded Nonstructural Protein 1 Modulates Cellular Apoptotic Machinery by Targeting Tumor Suppressor Protein p53. J Virol. 2013;87(12):6840–50.Perez JF, Chemello ME, Liprandi F, Ruiz M-C, Michelangeli F. Oncosis in MA104 Cells Is Induced by Rotavirus Infection through an Increase in Intracellular Ca2 + Concentration. Virology. 1998;252:17–27.Somersan S, Larsson M, Fonteneau JF, Basu S, Srivastava P, Bhardwaj N. Primary Tumor Tissue Lysates Are Enriched in Heat Shock Proteins and Induce the Maturation of Human Dendritic Cells. J Immunol. 2001;167(9):4844–52.Sen A, Ding S GB. The Role of Innate Immunity in Regulating Rotavirus Replication, Pathogenesis, and Host Range Restriction and the Implications for Live Rotaviral Vaccine Development. Mucosal Vaccines. 2020;(January):683–97.Di Fiore IJM, Holloway G, Coulson BS. Innate immune responses to rotavirus infection in macrophages depend on MAVS but involve neither the NLRP3 inflammasome nor JNK and p38 signaling pathways. Virus Res. 2015;208.Narváez CF, Angel J, Franco MA. Interaction of Rotavirus with Human Myeloid Dendritic Cells. J Virol. 2005;79(23).Estudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástricoAdministradoresBibliotecariosConsejerosEstudiantesGrupos comunitariosInvestigadoresMaestrosMedios de comunicaciónPadres y familiasPersonal de apoyo escolarProveedores de ayuda financiera para estudiantesPúblico generalReceptores de fondos federales y solicitantesResponsables políticosLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/83759/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL79564678.2022.pdf79564678.2022.pdfTesis de Doctorado en Biotecnologíaapplication/pdf72133290https://repositorio.unal.edu.co/bitstream/unal/83759/2/79564678.2022.pdfcaa5433f1cfdb45b21805abe3d23936dMD52THUMBNAIL79564678.2022.pdf.jpg79564678.2022.pdf.jpgGenerated Thumbnailimage/jpeg4668https://repositorio.unal.edu.co/bitstream/unal/83759/3/79564678.2022.pdf.jpgc4867b618b5a9e6bde4426842b975e48MD53unal/83759oai:repositorio.unal.edu.co:unal/837592023-08-03 23:03:44.708Repositorio Institucional Universidad Nacional de Colombiarepositorio_nal@unal.edu.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