{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:54:07Z","timestamp":1784609647551,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,18]],"date-time":"2019-08-18T00:00:00Z","timestamp":1566086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology","award":["MOST105-2320-B-019-005-MY3"],"award-info":[{"award-number":["MOST105-2320-B-019-005-MY3"]}]},{"name":"Ministry of Science and Technology","award":["NSC102-2628-B-019-001-MY3"],"award-info":[{"award-number":["NSC102-2628-B-019-001-MY3"]}]},{"name":"St. Mary\u2019s Junior College of Medicine, Nursing and Management","award":["SMC 108-1-11"],"award-info":[{"award-number":["SMC 108-1-11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Non-small-cell lung cancer (NSCLC) causes high mortality. Radiotherapy is an induction regimen generally applied to patients with NSCLC. In view of therapeutic efficacy, the outcome is not appealing in addition to bringing about unwanted side effects. Total nutrition is a new trend in cancer therapy, which benefits cancer patients under radiotherapy. Male C57BL\/6JNarl mice were experimentally divided into five groups: one control group, one T group (borne with Lewis lung carcinoma but no treatment), and three Lewis lung carcinoma-bearing groups administrated with a total nutrition formula (T + TNuF group), a local radiotherapy plus daily 3 Gy in three fractions (T + R group), or a combination TNuF and radiotherapy (T + R + TNuF group). These mice were assessed for their mean tumor volumes, cachectic symptoms and tumor metastasis. TNuF administration significantly suppressed tumor growth and activated apoptotic cell death in NSCLC-bearing mice under radiation. The body-weight gain was increased, while the radiation-induced cachexia was alleviated. Analysis of mechanisms suggests that TNuF downregulates EGFR and VEGF signaling pathways, inhibiting angiogenesis and metastasis. In light of radiation-induced tumor cell death, mitigation of radiation-induced cachexia and inhibition of tumor cell distant metastasis, the combination of TNuF and radiotherapy synergistically downregulates EGFR and VEGF signaling in NSCLC-bearing mice.<\/jats:p>","DOI":"10.3390\/nu11081944","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T06:10:14Z","timestamp":1566195014000},"page":"1944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Antitumor, Inhibition of Metastasis and Radiosensitizing Effects of Total Nutrition Formula on Lewis Tumor-Bearing Mice"],"prefix":"10.3390","volume":"11","author":[{"given":"Yu-Ming","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Radiation Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"School of Medicine, National Yang Ming University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Lin","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Life Science, Chinese Culture University, Taipei 11114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Han","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Food Science and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 20224, Taiwan"},{"name":"Division of Hemato-oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung 20401, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 33320, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Hsia","sequence":"additional","affiliation":[{"name":"Taiwan Nutraceutical Association, Taipei 10596, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Han","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Nursing, St. Mary\u2019s Junior College of Medicine, Nursing and Management, Yilan 26647, Taiwan"},{"name":"Institute of Long-Term Care, Mackay Medical College, New Taipei City 25245, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5079-5839","authenticated-orcid":false,"given":"Chang-Jer","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Food Science and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 20224, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan"},{"name":"Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.5334\/aogh.2419","article-title":"Global epidemiology of lung cancer","volume":"85","author":"Barta","year":"2019","journal-title":"Ann. Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1056\/NEJMra0802714","article-title":"Lung cancer","volume":"359","author":"Herbst","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.athoracsur.2017.07.032","article-title":"Postoperative outcome after pulmonary surgery for non-small cell lung cancer in elderly patients","volume":"105","author":"Detillon","year":"2018","journal-title":"Ann. Thorac. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1164\/rccm.200504-531OE","article-title":"One hundred years of lung cancer","volume":"172","author":"Spiro","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1002\/cncr.21778","article-title":"Metastatic patterns in adenocarcinoma","volume":"106","author":"Hess","year":"2006","journal-title":"Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.ctrv.2011.11.003","article-title":"Targeted agents in non-small cell lung cancer (NSCLC): Clinical developments and rationale for the combination with thoracic radiotherapy","volume":"38","author":"Koh","year":"2012","journal-title":"Cancer Treat. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0140-6736(13)61502-0","article-title":"Management of non-small-cell lung cancer: Recent developments","volume":"382","author":"Reck","year":"2013","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/S0360-3016(99)00130-3","article-title":"Effectiveness of accelerated radiotherapy for patients with inoperable non-small cell lung cancer (NSCLC) and borderline prognostic factors without distant metastasis: A retrospective review","volume":"44","author":"Nguyen","year":"1999","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.semcancer.2015.07.003","article-title":"Phosphatidylinositol 3-kinase\/Akt signaling as a key mediator of tumor cell responsiveness to radiation","volume":"35","author":"Toulany","year":"2015","journal-title":"Semin. Cancer Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.7326\/0003-4819-140-12-200406150-00015","article-title":"Medical management of the acute radiation syndrome: Recommendations of the strategic national stockpile radiation working group","volume":"140","author":"Waselenko","year":"2004","journal-title":"Ann. Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0169-5002(00)00156-2","article-title":"Predictive factors in radiotherapy for non-small cell lung cancer: Present status","volume":"31","author":"Choi","year":"2001","journal-title":"Lung Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0167-8140(00)00207-3","article-title":"The impact of three-dimensional radiation on the treatment of non-small cell lung cancer","volume":"56","author":"Armstrong","year":"2000","journal-title":"Radiother. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.ijrobp.2006.01.051","article-title":"Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC): Predictors for radiation pneumonitis and fibrosis","volume":"65","author":"Kong","year":"2006","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.ijrobp.2005.03.026","article-title":"Correlation of dosimetric factors and radiation pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study","volume":"63","author":"Yorke","year":"2005","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.semradonc.2006.11.009","article-title":"Normal tissue tolerance dose metrics for radiation therapy of major organs","volume":"17","author":"Milano","year":"2007","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1634\/theoncologist.2009-S101","article-title":"Targeting the TGF-beta1 pathway to prevent normal tissue injury after cancer therapy","volume":"15","author":"Anscher","year":"2010","journal-title":"Oncologist"},{"key":"ref_17","first-page":"1010428317695970","article-title":"Intracellular calcium promotes radioresistance of non-small cell lung cancer A549 cells through activating Akt signaling","volume":"39","author":"Wang","year":"2017","journal-title":"Tumor Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.radonc.2013.06.020","article-title":"High NOTCH activity induces radiation resistance in non small cell lung cancer","volume":"108","author":"Theys","year":"2013","journal-title":"Radiother. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.clnu.2013.04.005","article-title":"Interaction of \u03c9-3 polyunsaturated fatty acids with radiation therapy in two different colorectal cancer cell lines","volume":"33","author":"Cai","year":"2014","journal-title":"Clin. Nutr."},{"key":"ref_20","first-page":"688","article-title":"Soy isoflavones augment radiation effect by inhibiting APE1\/Ref-1 DNA repair activity in non small cell lung cancer","volume":"4","author":"Joiner","year":"2011","journal-title":"J. Thorac. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1002\/ijc.24015","article-title":"Radiation-induced HIF-1alpha cell survival pathway is inhibited by soy isoflavones in prostate cancer cells","volume":"124","author":"Zhang","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_22","first-page":"131","article-title":"Traditional chinese medicine curcumin sensitizes human colon cancer to radiation by altering the expression of DNA repair-related genes","volume":"38","author":"Yang","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1097\/JTO.0b013e3182208e90","article-title":"Nutrition during trimodality treatment in stage III non-small cell lung cancer: Not only important for underweight patients","volume":"6","author":"Phernambucq","year":"2011","journal-title":"J. Thorac. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1002\/hed.20221","article-title":"Impact of nutrition on outcome: A prospective randomized controlled trial in patients with head and neck cancer undergoing radiotherapy","volume":"27","author":"Ravasco","year":"2005","journal-title":"Head Neck"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1080\/01635581.2017.1359311","article-title":"Modified-nutrition index is a significant prognostic factor for the overall survival of the nasopharyngeal carcinoma patients who undergo intensity-modulated radiotherapy","volume":"69","author":"Hong","year":"2017","journal-title":"Nutr. Cancer"},{"key":"ref_26","first-page":"69","article-title":"Selenium is effective in inducing lymphocyte progression through cell cycle in cancer patients: Potential mechanisms for its activity","volume":"4","author":"Mantovani","year":"2004","journal-title":"J. Exp. Ther. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.jaad.2005.08.031","article-title":"Low plasma coenzyme Q10 levels as an independent prognostic factor for melanoma progression","volume":"54","author":"Rusciani","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1093\/annonc\/mdu587","article-title":"Baseline neutrophil-lymphocyte ratio (NLR) is associated with survival and response to treatment with second-line chemotherapy for advanced prostate cancer independent of baseline steroid use","volume":"26","author":"Lorente","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/bjc.2011.100","article-title":"Neutrophil\/lymphocyte ratio predicts chemotherapy outcomes in patients with advancedcolorectal cancer","volume":"104","author":"Chua","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nrc3007","article-title":"Strategies to improve radiotherapy with targeted drugs","volume":"11","author":"Begg","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.ejca.2007.01.034","article-title":"Ionising radiation induces changes associated with epithelial-mesenchymal transdifferentiation and increased cell motility of A549 lung epithelial cells","volume":"43","author":"Jung","year":"2007","journal-title":"Eur. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.addr.2016.02.002","article-title":"Cancer stem cells: Radioresistance, prediction of radiotherapy outcome and specific targets for combined treatments","volume":"109","author":"Krause","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1269\/jrr.45.253","article-title":"Cell killing and radiosensitization by caffeic acid phenethyl ester (CAPE) in lung cancer cells","volume":"45","author":"Chen","year":"2004","journal-title":"J. Radiat. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1269\/jrr.46.387","article-title":"Resveratrol enhances radiosensitivity of human non-small cell lung cancer NCI-H838 cells accompanied by inhibition of nuclear factor-kappa B activation","volume":"46","author":"Liao","year":"2005","journal-title":"J. Radiat. Res."},{"key":"ref_35","first-page":"489","article-title":"Enhancement of radiation response with combined ganoderma lucidum and duchesneachrysantha extracts in human leukemia HL-60 cells","volume":"21","author":"Kim","year":"2008","journal-title":"Int. J. Mol. Med."},{"key":"ref_36","first-page":"3163","article-title":"Effects of tetrandrine plus radiation on neuroblastoma cells","volume":"29","author":"Chen","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6651","DOI":"10.2147\/OTT.S96355","article-title":"The medicinal fungus Antrodia cinnamomea regulates DNA repair and enhances the radiosensitivity of human esophageal cancer cells","volume":"9","author":"Liu","year":"2016","journal-title":"Onco Targets Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1152\/physrev.00016.2008","article-title":"Mechanisms of cancer cachexia","volume":"89","author":"Tisdale","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.biopha.2013.08.005","article-title":"Malnutrition, anorexia and cachexia in cancer patients: A mini-review on pathogenesis and treatment","volume":"67","author":"Nicolini","year":"2013","journal-title":"Biomed. Pharmacother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/jcsm.12237","article-title":"Reduced dietary intake of micronutrients with antioxidant properties negatively impacts muscle health in aged mice","volume":"9","author":"Dijk","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"616","DOI":"10.4103\/0973-1482.147711","article-title":"Frequency of epidermal growth factor receptor mutations in Jordanian lung adenocarcinoma patients at diagnosis","volume":"12","author":"Obeidat","year":"2016","journal-title":"J. Cancer Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"C131","DOI":"10.4103\/0973-1482.200613","article-title":"Current mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors and updated therapy strategies in human nonsmall cell lung cancer","volume":"12","author":"Zhang","year":"2016","journal-title":"J. Cancer Res. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"907","DOI":"10.2174\/138161213804547259","article-title":"The intriguing interplay between therapies targeting the epidermal growth factor receptor, the hypoxic microenvironment and hypoxia-inducible factors","volume":"19","author":"Wouters","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/bjc.1991.286","article-title":"Differences in EGF related radiosensitisation of human squamous carcinoma cells with high and low numbers of EGF receptors","volume":"64","author":"Kwok","year":"1991","journal-title":"Br. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1089\/dna.2013.2249","article-title":"Relationship between serum VEGF level and radiosensitivity of patients with nonsmall cell lungcancer among Asians: A meta-analysis","volume":"33","author":"Fu","year":"2014","journal-title":"DNA Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1007\/s00066-014-0708-z","article-title":"Radiation-induced VEGF-C expression and endothelial cell proliferation in lung cancer","volume":"190","author":"Chen","year":"2014","journal-title":"Strahlenther. Onkol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.3892\/or.2017.5521","article-title":"125I seed irradiation induces apoptosis and inhibits angiogenesis by decreasing HIF-1\u03b1 and VEGF expression in lung carcinoma xenografts","volume":"37","author":"Xiang","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1093\/jn\/134.6.1536","article-title":"Dietary supplementation with high-selenium soy protein reduces pulmonary metastasis of melanoma cells in mice","volume":"134","author":"Li","year":"2004","journal-title":"J. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s12011-017-1188-7","article-title":"Dietary Supplementation with methylseleninic acid inhibits mammary tumorigenesis and metastasis in male MMTV-PyMT mice","volume":"184","author":"Sundaram","year":"2018","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.nano.2016.01.012","article-title":"RGD peptide-conjugated selenium nanoparticles: Antiangiogenesis by suppressing VEGF-VEGFR2-ERK\/AKT pathway","volume":"12","author":"Fu","year":"2016","journal-title":"Nanomedicine"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/8\/1944\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:12:02Z","timestamp":1760188322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/8\/1944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,18]]},"references-count":50,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["nu11081944"],"URL":"https:\/\/doi.org\/10.3390\/nu11081944","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,18]]}}}