Multisite Is Superior to Single-Site Intratumoral Chemotherapy to Retard the Outcomes of Pancreatic Ductal Adenocarcinoma in a Murine Model
Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion. This study explores the efficacy of multisite intratumoral injections in improving a drug&...
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| Veröffentlicht in: | Cancers 2023-12, Vol.15 (24), p.5801 |
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| creator | Lazarovits, Janette Epelbaum, Ron Lachter, Jesse Amikam, Yaron Ben Arie, Jacob |
| description | Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion.
This study explores the efficacy of multisite intratumoral injections in improving a drug's distribution while minimizing its side effects.
In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline (
< 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes (
< 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection (
= 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups (
= 0.007).
Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC. |
| doi_str_mv | 10.3390/cancers15245801 |
| format | Article |
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This study explores the efficacy of multisite intratumoral injections in improving a drug's distribution while minimizing its side effects.
In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline (
< 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes (
< 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection (
= 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups (
= 0.007).
Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers15245801</identifier><identifier>PMID: 38136347</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adenocarcinoma ; Animal models ; Animals ; Apoptosis ; Cancer ; Chemotherapy ; Clinical outcomes ; Comparative analysis ; Drug dosages ; Gemcitabine ; Health aspects ; Life span ; Lymphocytes ; Oncology, Experimental ; Oxaliplatin ; Pancreatic cancer ; Quality of life ; Stroma ; Toxicity ; Tumor microenvironment ; Tumors</subject><ispartof>Cancers, 2023-12, Vol.15 (24), p.5801</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-de6c19deb349b47b3c3ba9c38d0c470a3d8ba6cbee974fb4fef49fbedcb45b73</citedby><cites>FETCH-LOGICAL-c433t-de6c19deb349b47b3c3ba9c38d0c470a3d8ba6cbee974fb4fef49fbedcb45b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38136347$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lazarovits, Janette</creatorcontrib><creatorcontrib>Epelbaum, Ron</creatorcontrib><creatorcontrib>Lachter, Jesse</creatorcontrib><creatorcontrib>Amikam, Yaron</creatorcontrib><creatorcontrib>Ben Arie, Jacob</creatorcontrib><title>Multisite Is Superior to Single-Site Intratumoral Chemotherapy to Retard the Outcomes of Pancreatic Ductal Adenocarcinoma in a Murine Model</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion.
This study explores the efficacy of multisite intratumoral injections in improving a drug's distribution while minimizing its side effects.
In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline (
< 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes (
< 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection (
= 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups (
= 0.007).
Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC.</description><subject>Adenocarcinoma</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Cancer</subject><subject>Chemotherapy</subject><subject>Clinical outcomes</subject><subject>Comparative analysis</subject><subject>Drug dosages</subject><subject>Gemcitabine</subject><subject>Health aspects</subject><subject>Life span</subject><subject>Lymphocytes</subject><subject>Oncology, Experimental</subject><subject>Oxaliplatin</subject><subject>Pancreatic cancer</subject><subject>Quality of life</subject><subject>Stroma</subject><subject>Toxicity</subject><subject>Tumor microenvironment</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkk1P3DAQhqOqVUGUc2-VpV56CTixY8fH1ba0SKxALPfIH2MwSuytPw78hv5pvIV-odoHj2aed_TKM03zvsMnhAh8qqXXEFM39HQYcfeqOewx71vGBH39V3zQHKd0j-shpOOMv20OyNgRRig_bH5sypxdchnQeULbsoPoQkQ5oK3ztzO0258ln6PMZQlRzmh9B0vIdxDl7mEPXkOW0aCaQZcl67BAQsGiq-ougsxOo89F5ypcGfBBy6idD4tEziOJNiU6D2gTDMzvmjdWzgmOn9-j5ubsy836W3tx-fV8vbpoNSUktwaY7oQBRahQlCuiiZJCk9FgTTmWxIxKMq0ABKdWUQuWCqvAaEUHxclR8-mp7S6G7wVSnhaXNMyz9BBKmnqBh6ETnLOKfnyB3ocSfTW3p-jI6NCNf6hbOcPkvA31t_S-6bTinFPBGesrdfIfql4Di9PBg3U1_4_g9EmgY0gpgp120S0yPkwdnvYLML1YgKr48Gy3qAXMb_7XuMkjl1yuUg</recordid><startdate>20231201</startdate><enddate>20231201</enddate><creator>Lazarovits, Janette</creator><creator>Epelbaum, Ron</creator><creator>Lachter, Jesse</creator><creator>Amikam, Yaron</creator><creator>Ben Arie, Jacob</creator><general>MDPI AG</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</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>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20231201</creationdate><title>Multisite Is Superior to Single-Site Intratumoral Chemotherapy to Retard the Outcomes of Pancreatic Ductal Adenocarcinoma in a Murine Model</title><author>Lazarovits, Janette ; Epelbaum, Ron ; Lachter, Jesse ; Amikam, Yaron ; Ben Arie, Jacob</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-de6c19deb349b47b3c3ba9c38d0c470a3d8ba6cbee974fb4fef49fbedcb45b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adenocarcinoma</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Cancer</topic><topic>Chemotherapy</topic><topic>Clinical outcomes</topic><topic>Comparative analysis</topic><topic>Drug dosages</topic><topic>Gemcitabine</topic><topic>Health aspects</topic><topic>Life span</topic><topic>Lymphocytes</topic><topic>Oncology, Experimental</topic><topic>Oxaliplatin</topic><topic>Pancreatic cancer</topic><topic>Quality of life</topic><topic>Stroma</topic><topic>Toxicity</topic><topic>Tumor microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lazarovits, Janette</creatorcontrib><creatorcontrib>Epelbaum, Ron</creatorcontrib><creatorcontrib>Lachter, Jesse</creatorcontrib><creatorcontrib>Amikam, Yaron</creatorcontrib><creatorcontrib>Ben Arie, Jacob</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</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>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lazarovits, Janette</au><au>Epelbaum, Ron</au><au>Lachter, Jesse</au><au>Amikam, Yaron</au><au>Ben Arie, Jacob</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multisite Is Superior to Single-Site Intratumoral Chemotherapy to Retard the Outcomes of Pancreatic Ductal Adenocarcinoma in a Murine Model</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2023-12-01</date><risdate>2023</risdate><volume>15</volume><issue>24</issue><spage>5801</spage><pages>5801-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion.
This study explores the efficacy of multisite intratumoral injections in improving a drug's distribution while minimizing its side effects.
In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline (
< 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes (
< 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection (
= 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups (
= 0.007).
Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38136347</pmid><doi>10.3390/cancers15245801</doi><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Adenocarcinoma Animal models Animals Apoptosis Cancer Chemotherapy Clinical outcomes Comparative analysis Drug dosages Gemcitabine Health aspects Life span Lymphocytes Oncology, Experimental Oxaliplatin Pancreatic cancer Quality of life Stroma Toxicity Tumor microenvironment Tumors |
| title | Multisite Is Superior to Single-Site Intratumoral Chemotherapy to Retard the Outcomes of Pancreatic Ductal Adenocarcinoma in a Murine Model |
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