GK-1 peptide reduces tumor growth, decreases metastatic burden, and increases survival in a murine breast cancer model
•An anti-neoplastic effect of GK-1 in a murine breast cancer model is proposed.•The GK-1 effect relies on increasing IL-12 and necrosis at the primary tumor.•GK-1 reduces the concentration of pro-metastatic chemokines at the lungs. GK-1 is a parasite-derived peptide adjuvant of 18 amino acid-length...
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| Veröffentlicht in: | Vaccine 2017-10, Vol.35 (42), p.5653-5661 |
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| creator | Torres-García, D. Pérez-Torres, A. Manoutcharian, K. Orbe, U. Servín-Blanco, R. Fragoso, G. Sciutto, E. |
| description | •An anti-neoplastic effect of GK-1 in a murine breast cancer model is proposed.•The GK-1 effect relies on increasing IL-12 and necrosis at the primary tumor.•GK-1 reduces the concentration of pro-metastatic chemokines at the lungs.
GK-1 is a parasite-derived peptide adjuvant of 18 amino acid-length that enhances T-cell function and increases survival in B16-F10 melanoma tumor-bearing mice. This study was designed to evaluate in vivo the antitumor efficacy of GK-1 on 4T1 mouse mammary carcinoma.
BALB/c mice with palpable primary tumors were weekly intravenously injected three times with saline solution or three different concentrations (10, 50, or 100μg per mouse) of GK-1. GK-1 significantly increased lifespan (p |
| doi_str_mv | 10.1016/j.vaccine.2017.08.060 |
| format | Article |
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GK-1 is a parasite-derived peptide adjuvant of 18 amino acid-length that enhances T-cell function and increases survival in B16-F10 melanoma tumor-bearing mice. This study was designed to evaluate in vivo the antitumor efficacy of GK-1 on 4T1 mouse mammary carcinoma.
BALB/c mice with palpable primary tumors were weekly intravenously injected three times with saline solution or three different concentrations (10, 50, or 100μg per mouse) of GK-1. GK-1 significantly increased lifespan (p<0.0001) and reduced the primary tumor weight (p=0.014) and volume (p<0.0001) with respect to control mice, with no statistically significant differences among GK-1 doses. At the primary tumor, we found increased necrotic areas associated with a reduction in tumor mass, as well as an increase in the antitumor cytokine IL-12. Especially encouraging is the ability of GK-1 to reduce the number of lung metastasis (p=0.006) disregarding the dose used. The participation of IL-6 in metastasis development and the decreased levels of CCL-2, CCL-3, TNF-α, CXCL-9, GM-CSF, and b-FGF found in lungs of GK-1-treated mice is discussed.
Our study supports the effectiveness of GK-1 as an antineoplastic agent that merits further exploration in combination with other therapeutic approaches in future translational studies.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2017.08.060</identifier><identifier>PMID: 28890195</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Amino acids ; Angiogenesis ; Animals ; Anticancer properties ; Antigens ; Antineoplastic Agents - pharmacology ; Antitumor activity ; Breast cancer ; Breast Neoplasms ; Cancer therapies ; Carcinoma ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell survival ; Cytokines ; Disease Models, Animal ; Female ; Fibroblasts ; GK-1 ; Granulocyte-Macrophage Colony-Stimulating Factor ; Growth factors ; Immunotherapy ; Interleukin 12 ; Interleukin 6 ; Interleukin-12 - metabolism ; Interleukin-6 - metabolism ; Life span ; Lungs ; Lymphocytes T ; Mammary gland ; Mammary Neoplasms, Animal - drug therapy ; Melanoma ; Metastases ; Metastasis ; Mice ; Mice, Inbred BALB C ; Neoplasm Metastasis - pathology ; Parasites ; Peptides ; Peptides, Cyclic - pharmacology ; Primary tumor ; Rodents ; Statistical analysis ; Stem cells ; Survival ; Tumor necrosis factor ; Tumor Necrosis Factor-alpha - metabolism ; Tumors ; Weight reduction</subject><ispartof>Vaccine, 2017-10, Vol.35 (42), p.5653-5661</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Oct 9, 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-b530ded3e46dde6dcb9258d8ec66b904706ec43d1b2d3e52b5b7351b073debc83</citedby><cites>FETCH-LOGICAL-c393t-b530ded3e46dde6dcb9258d8ec66b904706ec43d1b2d3e52b5b7351b073debc83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1943089214?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28890195$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Torres-García, D.</creatorcontrib><creatorcontrib>Pérez-Torres, A.</creatorcontrib><creatorcontrib>Manoutcharian, K.</creatorcontrib><creatorcontrib>Orbe, U.</creatorcontrib><creatorcontrib>Servín-Blanco, R.</creatorcontrib><creatorcontrib>Fragoso, G.</creatorcontrib><creatorcontrib>Sciutto, E.</creatorcontrib><title>GK-1 peptide reduces tumor growth, decreases metastatic burden, and increases survival in a murine breast cancer model</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>•An anti-neoplastic effect of GK-1 in a murine breast cancer model is proposed.•The GK-1 effect relies on increasing IL-12 and necrosis at the primary tumor.•GK-1 reduces the concentration of pro-metastatic chemokines at the lungs.
GK-1 is a parasite-derived peptide adjuvant of 18 amino acid-length that enhances T-cell function and increases survival in B16-F10 melanoma tumor-bearing mice. This study was designed to evaluate in vivo the antitumor efficacy of GK-1 on 4T1 mouse mammary carcinoma.
BALB/c mice with palpable primary tumors were weekly intravenously injected three times with saline solution or three different concentrations (10, 50, or 100μg per mouse) of GK-1. GK-1 significantly increased lifespan (p<0.0001) and reduced the primary tumor weight (p=0.014) and volume (p<0.0001) with respect to control mice, with no statistically significant differences among GK-1 doses. At the primary tumor, we found increased necrotic areas associated with a reduction in tumor mass, as well as an increase in the antitumor cytokine IL-12. Especially encouraging is the ability of GK-1 to reduce the number of lung metastasis (p=0.006) disregarding the dose used. The participation of IL-6 in metastasis development and the decreased levels of CCL-2, CCL-3, TNF-α, CXCL-9, GM-CSF, and b-FGF found in lungs of GK-1-treated mice is discussed.
Our study supports the effectiveness of GK-1 as an antineoplastic agent that merits further exploration in combination with other therapeutic approaches in future translational studies.</description><subject>Amino acids</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Anticancer properties</subject><subject>Antigens</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antitumor activity</subject><subject>Breast cancer</subject><subject>Breast Neoplasms</subject><subject>Cancer therapies</subject><subject>Carcinoma</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell survival</subject><subject>Cytokines</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>GK-1</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor</subject><subject>Growth factors</subject><subject>Immunotherapy</subject><subject>Interleukin 12</subject><subject>Interleukin 6</subject><subject>Interleukin-12 - metabolism</subject><subject>Interleukin-6 - metabolism</subject><subject>Life span</subject><subject>Lungs</subject><subject>Lymphocytes T</subject><subject>Mammary gland</subject><subject>Mammary Neoplasms, Animal - drug therapy</subject><subject>Melanoma</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Neoplasm Metastasis - pathology</subject><subject>Parasites</subject><subject>Peptides</subject><subject>Peptides, Cyclic - pharmacology</subject><subject>Primary tumor</subject><subject>Rodents</subject><subject>Statistical analysis</subject><subject>Stem cells</subject><subject>Survival</subject><subject>Tumor necrosis factor</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Tumors</subject><subject>Weight reduction</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkUuLFDEQgIMo7rj6E5SAFw_bbaXTSScnkUVXccGLgreQR61m6MeYpFv892aYWQ9ePBVUffWgPkKeM2gZMPl6327W-zhj2wEbWlAtSHhAdkwNvOkEUw_JDjrZNz2DbxfkSc57ABCc6cfkolNKA9NiR7abTw2jBzyUGJAmDKvHTMs6LYl-T8uv8uOKBvQJba75CYvNxZboqVtTwPmK2jnQON8DeU1b3OxYU9TSaU31QOqOxUK9nT0mOi0Bx6fk0Z0dMz47x0vy9f27L9cfmtvPNx-v3942nmteGic4BAwcexkCyuCd7oQKCr2UTkM_gETf88BcVyHROeEGLpiDgQd0XvFL8uo095CWnyvmYqaYPY6jnXFZs2GaD4OQWoqKvvwH3S9rmut1leo5KN2xvlLiRPm05JzwzhxSnGz6bRiYoxizN2cx5ijGgDJVTO17cZ6-ugnD3657ExV4cwKwvmOLmEz2EevHQkzoiwlL_M-KP-5KoqY</recordid><startdate>20171009</startdate><enddate>20171009</enddate><creator>Torres-García, D.</creator><creator>Pérez-Torres, A.</creator><creator>Manoutcharian, K.</creator><creator>Orbe, U.</creator><creator>Servín-Blanco, R.</creator><creator>Fragoso, G.</creator><creator>Sciutto, E.</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20171009</creationdate><title>GK-1 peptide reduces tumor growth, decreases metastatic burden, and increases survival in a murine breast cancer model</title><author>Torres-García, D. ; Pérez-Torres, A. ; Manoutcharian, K. ; Orbe, U. ; Servín-Blanco, R. ; Fragoso, G. ; Sciutto, E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-b530ded3e46dde6dcb9258d8ec66b904706ec43d1b2d3e52b5b7351b073debc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Amino acids</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Anticancer properties</topic><topic>Antigens</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antitumor activity</topic><topic>Breast cancer</topic><topic>Breast Neoplasms</topic><topic>Cancer therapies</topic><topic>Carcinoma</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell survival</topic><topic>Cytokines</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>GK-1</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor</topic><topic>Growth factors</topic><topic>Immunotherapy</topic><topic>Interleukin 12</topic><topic>Interleukin 6</topic><topic>Interleukin-12 - metabolism</topic><topic>Interleukin-6 - metabolism</topic><topic>Life span</topic><topic>Lungs</topic><topic>Lymphocytes T</topic><topic>Mammary gland</topic><topic>Mammary Neoplasms, Animal - drug therapy</topic><topic>Melanoma</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Neoplasm Metastasis - pathology</topic><topic>Parasites</topic><topic>Peptides</topic><topic>Peptides, Cyclic - pharmacology</topic><topic>Primary tumor</topic><topic>Rodents</topic><topic>Statistical analysis</topic><topic>Stem cells</topic><topic>Survival</topic><topic>Tumor necrosis factor</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Tumors</topic><topic>Weight reduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Torres-García, D.</creatorcontrib><creatorcontrib>Pérez-Torres, A.</creatorcontrib><creatorcontrib>Manoutcharian, K.</creatorcontrib><creatorcontrib>Orbe, U.</creatorcontrib><creatorcontrib>Servín-Blanco, R.</creatorcontrib><creatorcontrib>Fragoso, G.</creatorcontrib><creatorcontrib>Sciutto, E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Torres-García, D.</au><au>Pérez-Torres, A.</au><au>Manoutcharian, K.</au><au>Orbe, U.</au><au>Servín-Blanco, R.</au><au>Fragoso, G.</au><au>Sciutto, E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GK-1 peptide reduces tumor growth, decreases metastatic burden, and increases survival in a murine breast cancer model</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2017-10-09</date><risdate>2017</risdate><volume>35</volume><issue>42</issue><spage>5653</spage><epage>5661</epage><pages>5653-5661</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>•An anti-neoplastic effect of GK-1 in a murine breast cancer model is proposed.•The GK-1 effect relies on increasing IL-12 and necrosis at the primary tumor.•GK-1 reduces the concentration of pro-metastatic chemokines at the lungs.
GK-1 is a parasite-derived peptide adjuvant of 18 amino acid-length that enhances T-cell function and increases survival in B16-F10 melanoma tumor-bearing mice. This study was designed to evaluate in vivo the antitumor efficacy of GK-1 on 4T1 mouse mammary carcinoma.
BALB/c mice with palpable primary tumors were weekly intravenously injected three times with saline solution or three different concentrations (10, 50, or 100μg per mouse) of GK-1. GK-1 significantly increased lifespan (p<0.0001) and reduced the primary tumor weight (p=0.014) and volume (p<0.0001) with respect to control mice, with no statistically significant differences among GK-1 doses. At the primary tumor, we found increased necrotic areas associated with a reduction in tumor mass, as well as an increase in the antitumor cytokine IL-12. Especially encouraging is the ability of GK-1 to reduce the number of lung metastasis (p=0.006) disregarding the dose used. The participation of IL-6 in metastasis development and the decreased levels of CCL-2, CCL-3, TNF-α, CXCL-9, GM-CSF, and b-FGF found in lungs of GK-1-treated mice is discussed.
Our study supports the effectiveness of GK-1 as an antineoplastic agent that merits further exploration in combination with other therapeutic approaches in future translational studies.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>28890195</pmid><doi>10.1016/j.vaccine.2017.08.060</doi><tpages>9</tpages></addata></record> |
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| subjects | Amino acids Angiogenesis Animals Anticancer properties Antigens Antineoplastic Agents - pharmacology Antitumor activity Breast cancer Breast Neoplasms Cancer therapies Carcinoma Cell Line, Tumor Cell Proliferation - drug effects Cell survival Cytokines Disease Models, Animal Female Fibroblasts GK-1 Granulocyte-Macrophage Colony-Stimulating Factor Growth factors Immunotherapy Interleukin 12 Interleukin 6 Interleukin-12 - metabolism Interleukin-6 - metabolism Life span Lungs Lymphocytes T Mammary gland Mammary Neoplasms, Animal - drug therapy Melanoma Metastases Metastasis Mice Mice, Inbred BALB C Neoplasm Metastasis - pathology Parasites Peptides Peptides, Cyclic - pharmacology Primary tumor Rodents Statistical analysis Stem cells Survival Tumor necrosis factor Tumor Necrosis Factor-alpha - metabolism Tumors Weight reduction |
| title | GK-1 peptide reduces tumor growth, decreases metastatic burden, and increases survival in a murine breast cancer model |
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