Blocking VCAM-1 inhibits pancreatic tumour progression and cancer-associated thrombosis/thromboembolism
ObjectivePancreatic ductal adenocarcinoma (PDAC) is the deadliest cancer. Cancer-associated thrombosis/thromboembolism (CAT), frequently observed in PDAC, is known as a poor prognostic factor. Here, we investigated the underlying mechanisms between PDAC and CAT, and performed a trial of therapeutic...
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| Veröffentlicht in: | Gut 2021-09, Vol.70 (9), p.1713-1723 |
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| creator | Sano, Makoto Takahashi, Ryota Ijichi, Hideaki Ishigaki, Kazunaga Yamada, Tomoharu Miyabayashi, Koji Kimura, Gen Mizuno, Suguru Kato, Hiroyuki Fujiwara, Hiroaki Nakatsuka, Takuma Tanaka, Yasuo Kim, Jinsuk Masugi, Yohei Morishita, Yasuyuki Tanaka, Mariko Ushiku, Tetsuo Nakai, Yousuke Tateishi, Keisuke Ishii, Yukimoto Isayama, Hiroyuki Moses, Harold L Koike, Kazuhiko |
| description | ObjectivePancreatic ductal adenocarcinoma (PDAC) is the deadliest cancer. Cancer-associated thrombosis/thromboembolism (CAT), frequently observed in PDAC, is known as a poor prognostic factor. Here, we investigated the underlying mechanisms between PDAC and CAT, and performed a trial of therapeutic approach for PDAC using a genetically engineered mouse model, PKF (Ptf1acre/+;LSL-KrasG12D/+;Tgfbr2flox/flox ).DesignPresence of CAT in PKF mice was detected by systemic autopsy. Plasma cytokines were screened by cytokine antibody array. Murine and human plasma atrial natriuretic peptide (ANP) and soluble vascular cell adhesion molecule 1 (sVCAM-1) were determined by ELISA. Distribution of VCAM-1 in PKF mice and human autopsy samples was detected by immunohistochemistry. PKF mice were treated with anti-VCAM-1 antibody and the effects on survival, distribution of CAT and the tumour histology were analysed.ResultsWe found spontaneous CAT with cardiomegaly in 68.4% PKF mice. Increase of plasma ANP and sVCAM-1 was observed in PKF mice and PDAC patients with CAT. VCAM-1 was detected in the activated endothelium and thrombi. Administration of anti-VCAM-1 antibody to PKF mice inhibited tumour growth, neutrophil/macrophage infiltration, tumour angiogenesis and progression of CAT; moreover, it dramatically extended survival (from 61 to 253 days, p |
| doi_str_mv | 10.1136/gutjnl-2020-320608 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2453692174</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2558938237</sourcerecordid><originalsourceid>FETCH-LOGICAL-b369t-96081a1d181d076ecae0970dc6b5dac74fffafb3352a5029ffd0ad6d590d43503</originalsourceid><addsrcrecordid>eNqNkctOxCAUhonR6Dj6Ai5MEzdu0AOUli514i3RuFG3hAIdGdsyQrvw7WXS0YUrF-QA-c5_Lj9CJwQuCGHF5XIcVn2LKVDAjEIBYgfNSF6I9BJiF80ASIl5mVcH6DDGFQAIUZF9dMAYiPQNM7S8br3-cP0ye1tcPWGSuf7d1W6I2Vr1Olg1OJ0NY-fHkK2DXwYbo_N9pnqT6UTYgFWMXjs1WJMN78F3tY8uXm6vNp3Wxe4I7TWqjfZ4G-fo9fbmZXGPH5_vHhZXj7hmRTXgKg1BFDFEEANlYbWyUJVgdFFzo3SZN02jmpoxThUHWjWNAWUKwyswOePA5uh80k3Nfo42DrJzUdu2Vb31Y5Q056kQJWWe0LM_6CpN2afuJOVcVExQViaKTpQOPsZgG7kOrlPhSxKQGxvkZIPc2CAnG1LS6VZ6rDtrflN-9p4APAF1t_qP4DfN7pSF</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2558938237</pqid></control><display><type>article</type><title>Blocking VCAM-1 inhibits pancreatic tumour progression and cancer-associated thrombosis/thromboembolism</title><source>MEDLINE</source><source>PubMed Central</source><creator>Sano, Makoto ; Takahashi, Ryota ; Ijichi, Hideaki ; Ishigaki, Kazunaga ; Yamada, Tomoharu ; Miyabayashi, Koji ; Kimura, Gen ; Mizuno, Suguru ; Kato, Hiroyuki ; Fujiwara, Hiroaki ; Nakatsuka, Takuma ; Tanaka, Yasuo ; Kim, Jinsuk ; Masugi, Yohei ; Morishita, Yasuyuki ; Tanaka, Mariko ; Ushiku, Tetsuo ; Nakai, Yousuke ; Tateishi, Keisuke ; Ishii, Yukimoto ; Isayama, Hiroyuki ; Moses, Harold L ; Koike, Kazuhiko</creator><creatorcontrib>Sano, Makoto ; Takahashi, Ryota ; Ijichi, Hideaki ; Ishigaki, Kazunaga ; Yamada, Tomoharu ; Miyabayashi, Koji ; Kimura, Gen ; Mizuno, Suguru ; Kato, Hiroyuki ; Fujiwara, Hiroaki ; Nakatsuka, Takuma ; Tanaka, Yasuo ; Kim, Jinsuk ; Masugi, Yohei ; Morishita, Yasuyuki ; Tanaka, Mariko ; Ushiku, Tetsuo ; Nakai, Yousuke ; Tateishi, Keisuke ; Ishii, Yukimoto ; Isayama, Hiroyuki ; Moses, Harold L ; Koike, Kazuhiko</creatorcontrib><description>ObjectivePancreatic ductal adenocarcinoma (PDAC) is the deadliest cancer. Cancer-associated thrombosis/thromboembolism (CAT), frequently observed in PDAC, is known as a poor prognostic factor. Here, we investigated the underlying mechanisms between PDAC and CAT, and performed a trial of therapeutic approach for PDAC using a genetically engineered mouse model, PKF (Ptf1acre/+;LSL-KrasG12D/+;Tgfbr2flox/flox ).DesignPresence of CAT in PKF mice was detected by systemic autopsy. Plasma cytokines were screened by cytokine antibody array. Murine and human plasma atrial natriuretic peptide (ANP) and soluble vascular cell adhesion molecule 1 (sVCAM-1) were determined by ELISA. Distribution of VCAM-1 in PKF mice and human autopsy samples was detected by immunohistochemistry. PKF mice were treated with anti-VCAM-1 antibody and the effects on survival, distribution of CAT and the tumour histology were analysed.ResultsWe found spontaneous CAT with cardiomegaly in 68.4% PKF mice. Increase of plasma ANP and sVCAM-1 was observed in PKF mice and PDAC patients with CAT. VCAM-1 was detected in the activated endothelium and thrombi. Administration of anti-VCAM-1 antibody to PKF mice inhibited tumour growth, neutrophil/macrophage infiltration, tumour angiogenesis and progression of CAT; moreover, it dramatically extended survival (from 61 to 253 days, p<0.01).ConclusionBlocking VCAM-1/sVCAM-1 might be a potent therapeutic approach for PDAC as well as CAT, which can contribute to the prognosis. Increase of plasma ANP and sVCAM-1 might be a diagnostic approach for CAT in PDAC.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gutjnl-2020-320608</identifier><identifier>PMID: 33087490</identifier><language>eng</language><publisher>England: BMJ Publishing Group LTD</publisher><subject>Adenocarcinoma ; Angiogenesis ; Animals ; Atrial natriuretic peptide ; Autopsy ; Blood clots ; Carcinoma, Pancreatic Ductal - complications ; Carcinoma, Pancreatic Ductal - pathology ; Carcinoma, Pancreatic Ductal - therapy ; Cell adhesion & migration ; Cell adhesion molecules ; Chemotherapy ; Cytokines ; Endothelium ; Enzyme-linked immunosorbent assay ; Female ; Genetic engineering ; Heart ; Humans ; Immunohistochemistry ; Leukocytes (neutrophilic) ; Macrophages ; Male ; Medical prognosis ; Metastases ; Mice ; Mice, Knockout ; Pancreas ; Pancreatic cancer ; Pancreatic Neoplasms - complications ; Pancreatic Neoplasms - pathology ; Pancreatic Neoplasms - therapy ; Peptides ; Plasma ; Pulmonary arteries ; Thromboembolism ; Thrombosis ; Thrombosis - etiology ; Thrombosis - prevention & control ; Tumor Microenvironment ; Tumor necrosis factor-TNF ; Tumors ; Vascular cell adhesion molecule 1 ; Vascular Cell Adhesion Molecule-1 - metabolism</subject><ispartof>Gut, 2021-09, Vol.70 (9), p.1713-1723</ispartof><rights>Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2021 Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b369t-96081a1d181d076ecae0970dc6b5dac74fffafb3352a5029ffd0ad6d590d43503</citedby><cites>FETCH-LOGICAL-b369t-96081a1d181d076ecae0970dc6b5dac74fffafb3352a5029ffd0ad6d590d43503</cites><orcidid>0000-0002-6952-4043 ; 0000-0002-2379-7986</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33087490$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sano, Makoto</creatorcontrib><creatorcontrib>Takahashi, Ryota</creatorcontrib><creatorcontrib>Ijichi, Hideaki</creatorcontrib><creatorcontrib>Ishigaki, Kazunaga</creatorcontrib><creatorcontrib>Yamada, Tomoharu</creatorcontrib><creatorcontrib>Miyabayashi, Koji</creatorcontrib><creatorcontrib>Kimura, Gen</creatorcontrib><creatorcontrib>Mizuno, Suguru</creatorcontrib><creatorcontrib>Kato, Hiroyuki</creatorcontrib><creatorcontrib>Fujiwara, Hiroaki</creatorcontrib><creatorcontrib>Nakatsuka, Takuma</creatorcontrib><creatorcontrib>Tanaka, Yasuo</creatorcontrib><creatorcontrib>Kim, Jinsuk</creatorcontrib><creatorcontrib>Masugi, Yohei</creatorcontrib><creatorcontrib>Morishita, Yasuyuki</creatorcontrib><creatorcontrib>Tanaka, Mariko</creatorcontrib><creatorcontrib>Ushiku, Tetsuo</creatorcontrib><creatorcontrib>Nakai, Yousuke</creatorcontrib><creatorcontrib>Tateishi, Keisuke</creatorcontrib><creatorcontrib>Ishii, Yukimoto</creatorcontrib><creatorcontrib>Isayama, Hiroyuki</creatorcontrib><creatorcontrib>Moses, Harold L</creatorcontrib><creatorcontrib>Koike, Kazuhiko</creatorcontrib><title>Blocking VCAM-1 inhibits pancreatic tumour progression and cancer-associated thrombosis/thromboembolism</title><title>Gut</title><addtitle>Gut</addtitle><description>ObjectivePancreatic ductal adenocarcinoma (PDAC) is the deadliest cancer. Cancer-associated thrombosis/thromboembolism (CAT), frequently observed in PDAC, is known as a poor prognostic factor. Here, we investigated the underlying mechanisms between PDAC and CAT, and performed a trial of therapeutic approach for PDAC using a genetically engineered mouse model, PKF (Ptf1acre/+;LSL-KrasG12D/+;Tgfbr2flox/flox ).DesignPresence of CAT in PKF mice was detected by systemic autopsy. Plasma cytokines were screened by cytokine antibody array. Murine and human plasma atrial natriuretic peptide (ANP) and soluble vascular cell adhesion molecule 1 (sVCAM-1) were determined by ELISA. Distribution of VCAM-1 in PKF mice and human autopsy samples was detected by immunohistochemistry. PKF mice were treated with anti-VCAM-1 antibody and the effects on survival, distribution of CAT and the tumour histology were analysed.ResultsWe found spontaneous CAT with cardiomegaly in 68.4% PKF mice. Increase of plasma ANP and sVCAM-1 was observed in PKF mice and PDAC patients with CAT. VCAM-1 was detected in the activated endothelium and thrombi. Administration of anti-VCAM-1 antibody to PKF mice inhibited tumour growth, neutrophil/macrophage infiltration, tumour angiogenesis and progression of CAT; moreover, it dramatically extended survival (from 61 to 253 days, p<0.01).ConclusionBlocking VCAM-1/sVCAM-1 might be a potent therapeutic approach for PDAC as well as CAT, which can contribute to the prognosis. Increase of plasma ANP and sVCAM-1 might be a diagnostic approach for CAT in PDAC.</description><subject>Adenocarcinoma</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Atrial natriuretic peptide</subject><subject>Autopsy</subject><subject>Blood clots</subject><subject>Carcinoma, Pancreatic Ductal - complications</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Carcinoma, Pancreatic Ductal - therapy</subject><subject>Cell adhesion & migration</subject><subject>Cell adhesion molecules</subject><subject>Chemotherapy</subject><subject>Cytokines</subject><subject>Endothelium</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Genetic engineering</subject><subject>Heart</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Leukocytes (neutrophilic)</subject><subject>Macrophages</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Pancreas</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - complications</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pancreatic Neoplasms - therapy</subject><subject>Peptides</subject><subject>Plasma</subject><subject>Pulmonary arteries</subject><subject>Thromboembolism</subject><subject>Thrombosis</subject><subject>Thrombosis - etiology</subject><subject>Thrombosis - prevention & control</subject><subject>Tumor Microenvironment</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumors</subject><subject>Vascular cell adhesion molecule 1</subject><subject>Vascular Cell Adhesion Molecule-1 - metabolism</subject><issn>0017-5749</issn><issn>1468-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkctOxCAUhonR6Dj6Ai5MEzdu0AOUli514i3RuFG3hAIdGdsyQrvw7WXS0YUrF-QA-c5_Lj9CJwQuCGHF5XIcVn2LKVDAjEIBYgfNSF6I9BJiF80ASIl5mVcH6DDGFQAIUZF9dMAYiPQNM7S8br3-cP0ye1tcPWGSuf7d1W6I2Vr1Olg1OJ0NY-fHkK2DXwYbo_N9pnqT6UTYgFWMXjs1WJMN78F3tY8uXm6vNp3Wxe4I7TWqjfZ4G-fo9fbmZXGPH5_vHhZXj7hmRTXgKg1BFDFEEANlYbWyUJVgdFFzo3SZN02jmpoxThUHWjWNAWUKwyswOePA5uh80k3Nfo42DrJzUdu2Vb31Y5Q056kQJWWe0LM_6CpN2afuJOVcVExQViaKTpQOPsZgG7kOrlPhSxKQGxvkZIPc2CAnG1LS6VZ6rDtrflN-9p4APAF1t_qP4DfN7pSF</recordid><startdate>202109</startdate><enddate>202109</enddate><creator>Sano, Makoto</creator><creator>Takahashi, Ryota</creator><creator>Ijichi, Hideaki</creator><creator>Ishigaki, Kazunaga</creator><creator>Yamada, Tomoharu</creator><creator>Miyabayashi, Koji</creator><creator>Kimura, Gen</creator><creator>Mizuno, Suguru</creator><creator>Kato, Hiroyuki</creator><creator>Fujiwara, Hiroaki</creator><creator>Nakatsuka, Takuma</creator><creator>Tanaka, Yasuo</creator><creator>Kim, Jinsuk</creator><creator>Masugi, Yohei</creator><creator>Morishita, Yasuyuki</creator><creator>Tanaka, Mariko</creator><creator>Ushiku, Tetsuo</creator><creator>Nakai, Yousuke</creator><creator>Tateishi, Keisuke</creator><creator>Ishii, Yukimoto</creator><creator>Isayama, Hiroyuki</creator><creator>Moses, Harold L</creator><creator>Koike, Kazuhiko</creator><general>BMJ Publishing Group LTD</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6952-4043</orcidid><orcidid>https://orcid.org/0000-0002-2379-7986</orcidid></search><sort><creationdate>202109</creationdate><title>Blocking VCAM-1 inhibits pancreatic tumour progression and cancer-associated thrombosis/thromboembolism</title><author>Sano, Makoto ; Takahashi, Ryota ; Ijichi, Hideaki ; Ishigaki, Kazunaga ; Yamada, Tomoharu ; Miyabayashi, Koji ; Kimura, Gen ; Mizuno, Suguru ; Kato, Hiroyuki ; Fujiwara, Hiroaki ; Nakatsuka, Takuma ; Tanaka, Yasuo ; Kim, Jinsuk ; Masugi, Yohei ; Morishita, Yasuyuki ; Tanaka, Mariko ; Ushiku, Tetsuo ; Nakai, Yousuke ; Tateishi, Keisuke ; Ishii, Yukimoto ; Isayama, Hiroyuki ; Moses, Harold L ; Koike, Kazuhiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b369t-96081a1d181d076ecae0970dc6b5dac74fffafb3352a5029ffd0ad6d590d43503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenocarcinoma</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Atrial natriuretic peptide</topic><topic>Autopsy</topic><topic>Blood clots</topic><topic>Carcinoma, Pancreatic Ductal - complications</topic><topic>Carcinoma, Pancreatic Ductal - pathology</topic><topic>Carcinoma, Pancreatic Ductal - therapy</topic><topic>Cell adhesion & migration</topic><topic>Cell adhesion molecules</topic><topic>Chemotherapy</topic><topic>Cytokines</topic><topic>Endothelium</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Female</topic><topic>Genetic engineering</topic><topic>Heart</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Leukocytes (neutrophilic)</topic><topic>Macrophages</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Pancreas</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - complications</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Pancreatic Neoplasms - therapy</topic><topic>Peptides</topic><topic>Plasma</topic><topic>Pulmonary arteries</topic><topic>Thromboembolism</topic><topic>Thrombosis</topic><topic>Thrombosis - etiology</topic><topic>Thrombosis - prevention & control</topic><topic>Tumor Microenvironment</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumors</topic><topic>Vascular cell adhesion molecule 1</topic><topic>Vascular Cell Adhesion Molecule-1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sano, Makoto</creatorcontrib><creatorcontrib>Takahashi, Ryota</creatorcontrib><creatorcontrib>Ijichi, Hideaki</creatorcontrib><creatorcontrib>Ishigaki, Kazunaga</creatorcontrib><creatorcontrib>Yamada, Tomoharu</creatorcontrib><creatorcontrib>Miyabayashi, Koji</creatorcontrib><creatorcontrib>Kimura, Gen</creatorcontrib><creatorcontrib>Mizuno, Suguru</creatorcontrib><creatorcontrib>Kato, Hiroyuki</creatorcontrib><creatorcontrib>Fujiwara, Hiroaki</creatorcontrib><creatorcontrib>Nakatsuka, Takuma</creatorcontrib><creatorcontrib>Tanaka, Yasuo</creatorcontrib><creatorcontrib>Kim, Jinsuk</creatorcontrib><creatorcontrib>Masugi, Yohei</creatorcontrib><creatorcontrib>Morishita, Yasuyuki</creatorcontrib><creatorcontrib>Tanaka, Mariko</creatorcontrib><creatorcontrib>Ushiku, Tetsuo</creatorcontrib><creatorcontrib>Nakai, Yousuke</creatorcontrib><creatorcontrib>Tateishi, Keisuke</creatorcontrib><creatorcontrib>Ishii, Yukimoto</creatorcontrib><creatorcontrib>Isayama, Hiroyuki</creatorcontrib><creatorcontrib>Moses, Harold L</creatorcontrib><creatorcontrib>Koike, Kazuhiko</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM 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>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>BMJ Journals</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science 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 China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sano, Makoto</au><au>Takahashi, Ryota</au><au>Ijichi, Hideaki</au><au>Ishigaki, Kazunaga</au><au>Yamada, Tomoharu</au><au>Miyabayashi, Koji</au><au>Kimura, Gen</au><au>Mizuno, Suguru</au><au>Kato, Hiroyuki</au><au>Fujiwara, Hiroaki</au><au>Nakatsuka, Takuma</au><au>Tanaka, Yasuo</au><au>Kim, Jinsuk</au><au>Masugi, Yohei</au><au>Morishita, Yasuyuki</au><au>Tanaka, Mariko</au><au>Ushiku, Tetsuo</au><au>Nakai, Yousuke</au><au>Tateishi, Keisuke</au><au>Ishii, Yukimoto</au><au>Isayama, Hiroyuki</au><au>Moses, Harold L</au><au>Koike, Kazuhiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Blocking VCAM-1 inhibits pancreatic tumour progression and cancer-associated thrombosis/thromboembolism</atitle><jtitle>Gut</jtitle><addtitle>Gut</addtitle><date>2021-09</date><risdate>2021</risdate><volume>70</volume><issue>9</issue><spage>1713</spage><epage>1723</epage><pages>1713-1723</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><abstract>ObjectivePancreatic ductal adenocarcinoma (PDAC) is the deadliest cancer. Cancer-associated thrombosis/thromboembolism (CAT), frequently observed in PDAC, is known as a poor prognostic factor. Here, we investigated the underlying mechanisms between PDAC and CAT, and performed a trial of therapeutic approach for PDAC using a genetically engineered mouse model, PKF (Ptf1acre/+;LSL-KrasG12D/+;Tgfbr2flox/flox ).DesignPresence of CAT in PKF mice was detected by systemic autopsy. Plasma cytokines were screened by cytokine antibody array. Murine and human plasma atrial natriuretic peptide (ANP) and soluble vascular cell adhesion molecule 1 (sVCAM-1) were determined by ELISA. Distribution of VCAM-1 in PKF mice and human autopsy samples was detected by immunohistochemistry. PKF mice were treated with anti-VCAM-1 antibody and the effects on survival, distribution of CAT and the tumour histology were analysed.ResultsWe found spontaneous CAT with cardiomegaly in 68.4% PKF mice. Increase of plasma ANP and sVCAM-1 was observed in PKF mice and PDAC patients with CAT. VCAM-1 was detected in the activated endothelium and thrombi. Administration of anti-VCAM-1 antibody to PKF mice inhibited tumour growth, neutrophil/macrophage infiltration, tumour angiogenesis and progression of CAT; moreover, it dramatically extended survival (from 61 to 253 days, p<0.01).ConclusionBlocking VCAM-1/sVCAM-1 might be a potent therapeutic approach for PDAC as well as CAT, which can contribute to the prognosis. Increase of plasma ANP and sVCAM-1 might be a diagnostic approach for CAT in PDAC.</abstract><cop>England</cop><pub>BMJ Publishing Group LTD</pub><pmid>33087490</pmid><doi>10.1136/gutjnl-2020-320608</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-6952-4043</orcidid><orcidid>https://orcid.org/0000-0002-2379-7986</orcidid></addata></record> |
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| ispartof | Gut, 2021-09, Vol.70 (9), p.1713-1723 |
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| subjects | Adenocarcinoma Angiogenesis Animals Atrial natriuretic peptide Autopsy Blood clots Carcinoma, Pancreatic Ductal - complications Carcinoma, Pancreatic Ductal - pathology Carcinoma, Pancreatic Ductal - therapy Cell adhesion & migration Cell adhesion molecules Chemotherapy Cytokines Endothelium Enzyme-linked immunosorbent assay Female Genetic engineering Heart Humans Immunohistochemistry Leukocytes (neutrophilic) Macrophages Male Medical prognosis Metastases Mice Mice, Knockout Pancreas Pancreatic cancer Pancreatic Neoplasms - complications Pancreatic Neoplasms - pathology Pancreatic Neoplasms - therapy Peptides Plasma Pulmonary arteries Thromboembolism Thrombosis Thrombosis - etiology Thrombosis - prevention & control Tumor Microenvironment Tumor necrosis factor-TNF Tumors Vascular cell adhesion molecule 1 Vascular Cell Adhesion Molecule-1 - metabolism |
| title | Blocking VCAM-1 inhibits pancreatic tumour progression and cancer-associated thrombosis/thromboembolism |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T05%3A02%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Blocking%20VCAM-1%20inhibits%20pancreatic%20tumour%20progression%20and%20cancer-associated%20thrombosis/thromboembolism&rft.jtitle=Gut&rft.au=Sano,%20Makoto&rft.date=2021-09&rft.volume=70&rft.issue=9&rft.spage=1713&rft.epage=1723&rft.pages=1713-1723&rft.issn=0017-5749&rft.eissn=1468-3288&rft_id=info:doi/10.1136/gutjnl-2020-320608&rft_dat=%3Cproquest_cross%3E2558938237%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2558938237&rft_id=info:pmid/33087490&rfr_iscdi=true |