Hedgehog signaling pathway is a possible therapeutic target for gastric cancer
Background and Objectives It has been shown that the hedgehog (Hh) signaling pathway is activated in gastric cancer. To investigate the viability of the Hh pathway as a therapeutic target, we analyzed activation of the Hh pathway in gastric cancer. Methods Surgically resected gastric carcinoma speci...
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| Veröffentlicht in: | Journal of surgical oncology 2007-01, Vol.95 (1), p.55-62 |
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| creator | Yanai, Kosuke Nagai, Shuntaro Wada, Junji Yamanaka, Naoki Nakamura, Masafumi Torata, Nobuhiro Noshiro, Hirokazu Tsuneyoshi, Masazumi Tanaka, Masao Katano, Mitsuo |
| description | Background and Objectives
It has been shown that the hedgehog (Hh) signaling pathway is activated in gastric cancer. To investigate the viability of the Hh pathway as a therapeutic target, we analyzed activation of the Hh pathway in gastric cancer.
Methods
Surgically resected gastric carcinoma specimens and lymph nodes were analyzed immunohistochemically. We used the percentage of cancer cells with nuclear translocation of Gli1 as a marker of Hh pathway activation.
Results
Nuclear localization of Gli1 was higher in 28 undifferentiated‐type tumors than in 30 differentiated‐type tumors. Eighteen of the fifty‐eight cancer specimens consisted of a mixture of a histologically predominant part and a small area with different histology. In these 18 tumors, the percentage of cells showing nuclear staining of Gli1 was higher in the undifferentiated‐type part than in the differentiated‐type part. Nuclear staining of Gli1 in primary tumors was positively correlated with lymph node metastasis. The Gli1 nuclear staining percentage of metastatic lymph nodes correlated closely with that of each primary carcinoma. Cyclopamine, a Hh pathway inhibitor, suppressed the growth of gastric cancer cells in vitro.
Conclusions
The Hh pathway may be a useful therapeutic target for such as undifferentiated‐type gastric cancer with lymph node metastasis. J. Surg. Oncol. 2007;95:55–62. © 2006 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/jso.20606 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68388799</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>68388799</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4276-b774ca612fba2721a962a4ad122b02f04fdbb1a8f510d9257791e77ace4281e83</originalsourceid><addsrcrecordid>eNp1kMtOwzAQRS0EglJY8APIKyQWAdtJ7XiJEFBQacVLXVqTZJIa0ibYqUr_nkAKrFiNNHPukeYScsTZGWdMnL_66kwwyeQW6XGmZaCZjrdJr72JIFKa7ZF9718ZY1rLaJfsccW1iKXqkfEQswJnVUG9LRZQ2kVBa2hmK1hT6ynQuvLeJiXSZoYOalw2NqUNuAIbmleOFuAb165SWKToDshODqXHw83sk5frq-fLYTCa3NxeXoyCNBJKBolSUQqSizwBoQQHLQVEkHEhEiZyFuVZknCI8wFnmRYDpTRHpSDFSMQc47BPTjpv7ar3JfrGzK1PsSxhgdXSGxmHcay0bsHTDkxd-4jD3NTOzsGtDWfmqzzTlme-y2vZ4410mcwx-yM3bbXAeQesbInr_03m7mnyowy6hPUNfvwmwL2Z1qcGZjq-Mdf3D4_TaTg2w_ATAUKIeg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>68388799</pqid></control><display><type>article</type><title>Hedgehog signaling pathway is a possible therapeutic target for gastric cancer</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Yanai, Kosuke ; Nagai, Shuntaro ; Wada, Junji ; Yamanaka, Naoki ; Nakamura, Masafumi ; Torata, Nobuhiro ; Noshiro, Hirokazu ; Tsuneyoshi, Masazumi ; Tanaka, Masao ; Katano, Mitsuo</creator><creatorcontrib>Yanai, Kosuke ; Nagai, Shuntaro ; Wada, Junji ; Yamanaka, Naoki ; Nakamura, Masafumi ; Torata, Nobuhiro ; Noshiro, Hirokazu ; Tsuneyoshi, Masazumi ; Tanaka, Masao ; Katano, Mitsuo</creatorcontrib><description>Background and Objectives
It has been shown that the hedgehog (Hh) signaling pathway is activated in gastric cancer. To investigate the viability of the Hh pathway as a therapeutic target, we analyzed activation of the Hh pathway in gastric cancer.
Methods
Surgically resected gastric carcinoma specimens and lymph nodes were analyzed immunohistochemically. We used the percentage of cancer cells with nuclear translocation of Gli1 as a marker of Hh pathway activation.
Results
Nuclear localization of Gli1 was higher in 28 undifferentiated‐type tumors than in 30 differentiated‐type tumors. Eighteen of the fifty‐eight cancer specimens consisted of a mixture of a histologically predominant part and a small area with different histology. In these 18 tumors, the percentage of cells showing nuclear staining of Gli1 was higher in the undifferentiated‐type part than in the differentiated‐type part. Nuclear staining of Gli1 in primary tumors was positively correlated with lymph node metastasis. The Gli1 nuclear staining percentage of metastatic lymph nodes correlated closely with that of each primary carcinoma. Cyclopamine, a Hh pathway inhibitor, suppressed the growth of gastric cancer cells in vitro.
Conclusions
The Hh pathway may be a useful therapeutic target for such as undifferentiated‐type gastric cancer with lymph node metastasis. J. Surg. Oncol. 2007;95:55–62. © 2006 Wiley‐Liss, Inc.</description><identifier>ISSN: 0022-4790</identifier><identifier>EISSN: 1096-9098</identifier><identifier>DOI: 10.1002/jso.20606</identifier><identifier>PMID: 17192867</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Adenocarcinoma - secondary ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Signet Ring Cell - metabolism ; Carcinoma, Signet Ring Cell - pathology ; Carcinoma, Signet Ring Cell - secondary ; Cell Line, Tumor ; Female ; gastric cancer ; Gli1 ; Hedgehog Proteins - physiology ; hedgehog signaling ; histologic heterogeneity ; Humans ; lymph node metastasis ; Lymph Nodes - metabolism ; Lymph Nodes - pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Oncogene Proteins - analysis ; Oncogene Proteins - genetics ; Receptors, Cell Surface - metabolism ; Signal Transduction - physiology ; Stomach Neoplasms - metabolism ; Stomach Neoplasms - pathology ; Trans-Activators - analysis ; Trans-Activators - genetics ; Trans-Activators - physiology ; Transcription Factors - metabolism ; Zinc Finger Protein GLI1</subject><ispartof>Journal of surgical oncology, 2007-01, Vol.95 (1), p.55-62</ispartof><rights>Copyright © 2006 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4276-b774ca612fba2721a962a4ad122b02f04fdbb1a8f510d9257791e77ace4281e83</citedby><cites>FETCH-LOGICAL-c4276-b774ca612fba2721a962a4ad122b02f04fdbb1a8f510d9257791e77ace4281e83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjso.20606$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjso.20606$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17192867$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yanai, Kosuke</creatorcontrib><creatorcontrib>Nagai, Shuntaro</creatorcontrib><creatorcontrib>Wada, Junji</creatorcontrib><creatorcontrib>Yamanaka, Naoki</creatorcontrib><creatorcontrib>Nakamura, Masafumi</creatorcontrib><creatorcontrib>Torata, Nobuhiro</creatorcontrib><creatorcontrib>Noshiro, Hirokazu</creatorcontrib><creatorcontrib>Tsuneyoshi, Masazumi</creatorcontrib><creatorcontrib>Tanaka, Masao</creatorcontrib><creatorcontrib>Katano, Mitsuo</creatorcontrib><title>Hedgehog signaling pathway is a possible therapeutic target for gastric cancer</title><title>Journal of surgical oncology</title><addtitle>J. Surg. Oncol</addtitle><description>Background and Objectives
It has been shown that the hedgehog (Hh) signaling pathway is activated in gastric cancer. To investigate the viability of the Hh pathway as a therapeutic target, we analyzed activation of the Hh pathway in gastric cancer.
Methods
Surgically resected gastric carcinoma specimens and lymph nodes were analyzed immunohistochemically. We used the percentage of cancer cells with nuclear translocation of Gli1 as a marker of Hh pathway activation.
Results
Nuclear localization of Gli1 was higher in 28 undifferentiated‐type tumors than in 30 differentiated‐type tumors. Eighteen of the fifty‐eight cancer specimens consisted of a mixture of a histologically predominant part and a small area with different histology. In these 18 tumors, the percentage of cells showing nuclear staining of Gli1 was higher in the undifferentiated‐type part than in the differentiated‐type part. Nuclear staining of Gli1 in primary tumors was positively correlated with lymph node metastasis. The Gli1 nuclear staining percentage of metastatic lymph nodes correlated closely with that of each primary carcinoma. Cyclopamine, a Hh pathway inhibitor, suppressed the growth of gastric cancer cells in vitro.
Conclusions
The Hh pathway may be a useful therapeutic target for such as undifferentiated‐type gastric cancer with lymph node metastasis. J. Surg. Oncol. 2007;95:55–62. © 2006 Wiley‐Liss, Inc.</description><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma - secondary</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Carcinoma, Signet Ring Cell - metabolism</subject><subject>Carcinoma, Signet Ring Cell - pathology</subject><subject>Carcinoma, Signet Ring Cell - secondary</subject><subject>Cell Line, Tumor</subject><subject>Female</subject><subject>gastric cancer</subject><subject>Gli1</subject><subject>Hedgehog Proteins - physiology</subject><subject>hedgehog signaling</subject><subject>histologic heterogeneity</subject><subject>Humans</subject><subject>lymph node metastasis</subject><subject>Lymph Nodes - metabolism</subject><subject>Lymph Nodes - pathology</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Invasiveness</subject><subject>Oncogene Proteins - analysis</subject><subject>Oncogene Proteins - genetics</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Signal Transduction - physiology</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Stomach Neoplasms - pathology</subject><subject>Trans-Activators - analysis</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - physiology</subject><subject>Transcription Factors - metabolism</subject><subject>Zinc Finger Protein GLI1</subject><issn>0022-4790</issn><issn>1096-9098</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtOwzAQRS0EglJY8APIKyQWAdtJ7XiJEFBQacVLXVqTZJIa0ibYqUr_nkAKrFiNNHPukeYScsTZGWdMnL_66kwwyeQW6XGmZaCZjrdJr72JIFKa7ZF9718ZY1rLaJfsccW1iKXqkfEQswJnVUG9LRZQ2kVBa2hmK1hT6ynQuvLeJiXSZoYOalw2NqUNuAIbmleOFuAb165SWKToDshODqXHw83sk5frq-fLYTCa3NxeXoyCNBJKBolSUQqSizwBoQQHLQVEkHEhEiZyFuVZknCI8wFnmRYDpTRHpSDFSMQc47BPTjpv7ar3JfrGzK1PsSxhgdXSGxmHcay0bsHTDkxd-4jD3NTOzsGtDWfmqzzTlme-y2vZ4410mcwx-yM3bbXAeQesbInr_03m7mnyowy6hPUNfvwmwL2Z1qcGZjq-Mdf3D4_TaTg2w_ATAUKIeg</recordid><startdate>20070101</startdate><enddate>20070101</enddate><creator>Yanai, Kosuke</creator><creator>Nagai, Shuntaro</creator><creator>Wada, Junji</creator><creator>Yamanaka, Naoki</creator><creator>Nakamura, Masafumi</creator><creator>Torata, Nobuhiro</creator><creator>Noshiro, Hirokazu</creator><creator>Tsuneyoshi, Masazumi</creator><creator>Tanaka, Masao</creator><creator>Katano, Mitsuo</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><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>7X8</scope></search><sort><creationdate>20070101</creationdate><title>Hedgehog signaling pathway is a possible therapeutic target for gastric cancer</title><author>Yanai, Kosuke ; Nagai, Shuntaro ; Wada, Junji ; Yamanaka, Naoki ; Nakamura, Masafumi ; Torata, Nobuhiro ; Noshiro, Hirokazu ; Tsuneyoshi, Masazumi ; Tanaka, Masao ; Katano, Mitsuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4276-b774ca612fba2721a962a4ad122b02f04fdbb1a8f510d9257791e77ace4281e83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenocarcinoma - secondary</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Carcinoma, Signet Ring Cell - metabolism</topic><topic>Carcinoma, Signet Ring Cell - pathology</topic><topic>Carcinoma, Signet Ring Cell - secondary</topic><topic>Cell Line, Tumor</topic><topic>Female</topic><topic>gastric cancer</topic><topic>Gli1</topic><topic>Hedgehog Proteins - physiology</topic><topic>hedgehog signaling</topic><topic>histologic heterogeneity</topic><topic>Humans</topic><topic>lymph node metastasis</topic><topic>Lymph Nodes - metabolism</topic><topic>Lymph Nodes - pathology</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Invasiveness</topic><topic>Oncogene Proteins - analysis</topic><topic>Oncogene Proteins - genetics</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Signal Transduction - physiology</topic><topic>Stomach Neoplasms - metabolism</topic><topic>Stomach Neoplasms - pathology</topic><topic>Trans-Activators - analysis</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - physiology</topic><topic>Transcription Factors - metabolism</topic><topic>Zinc Finger Protein GLI1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yanai, Kosuke</creatorcontrib><creatorcontrib>Nagai, Shuntaro</creatorcontrib><creatorcontrib>Wada, Junji</creatorcontrib><creatorcontrib>Yamanaka, Naoki</creatorcontrib><creatorcontrib>Nakamura, Masafumi</creatorcontrib><creatorcontrib>Torata, Nobuhiro</creatorcontrib><creatorcontrib>Noshiro, Hirokazu</creatorcontrib><creatorcontrib>Tsuneyoshi, Masazumi</creatorcontrib><creatorcontrib>Tanaka, Masao</creatorcontrib><creatorcontrib>Katano, Mitsuo</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of surgical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yanai, Kosuke</au><au>Nagai, Shuntaro</au><au>Wada, Junji</au><au>Yamanaka, Naoki</au><au>Nakamura, Masafumi</au><au>Torata, Nobuhiro</au><au>Noshiro, Hirokazu</au><au>Tsuneyoshi, Masazumi</au><au>Tanaka, Masao</au><au>Katano, Mitsuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hedgehog signaling pathway is a possible therapeutic target for gastric cancer</atitle><jtitle>Journal of surgical oncology</jtitle><addtitle>J. Surg. Oncol</addtitle><date>2007-01-01</date><risdate>2007</risdate><volume>95</volume><issue>1</issue><spage>55</spage><epage>62</epage><pages>55-62</pages><issn>0022-4790</issn><eissn>1096-9098</eissn><abstract>Background and Objectives
It has been shown that the hedgehog (Hh) signaling pathway is activated in gastric cancer. To investigate the viability of the Hh pathway as a therapeutic target, we analyzed activation of the Hh pathway in gastric cancer.
Methods
Surgically resected gastric carcinoma specimens and lymph nodes were analyzed immunohistochemically. We used the percentage of cancer cells with nuclear translocation of Gli1 as a marker of Hh pathway activation.
Results
Nuclear localization of Gli1 was higher in 28 undifferentiated‐type tumors than in 30 differentiated‐type tumors. Eighteen of the fifty‐eight cancer specimens consisted of a mixture of a histologically predominant part and a small area with different histology. In these 18 tumors, the percentage of cells showing nuclear staining of Gli1 was higher in the undifferentiated‐type part than in the differentiated‐type part. Nuclear staining of Gli1 in primary tumors was positively correlated with lymph node metastasis. The Gli1 nuclear staining percentage of metastatic lymph nodes correlated closely with that of each primary carcinoma. Cyclopamine, a Hh pathway inhibitor, suppressed the growth of gastric cancer cells in vitro.
Conclusions
The Hh pathway may be a useful therapeutic target for such as undifferentiated‐type gastric cancer with lymph node metastasis. J. Surg. Oncol. 2007;95:55–62. © 2006 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>17192867</pmid><doi>10.1002/jso.20606</doi><tpages>8</tpages></addata></record> |
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| subjects | Adenocarcinoma - metabolism Adenocarcinoma - pathology Adenocarcinoma - secondary Adult Aged Aged, 80 and over Carcinoma, Signet Ring Cell - metabolism Carcinoma, Signet Ring Cell - pathology Carcinoma, Signet Ring Cell - secondary Cell Line, Tumor Female gastric cancer Gli1 Hedgehog Proteins - physiology hedgehog signaling histologic heterogeneity Humans lymph node metastasis Lymph Nodes - metabolism Lymph Nodes - pathology Lymphatic Metastasis Male Middle Aged Neoplasm Invasiveness Oncogene Proteins - analysis Oncogene Proteins - genetics Receptors, Cell Surface - metabolism Signal Transduction - physiology Stomach Neoplasms - metabolism Stomach Neoplasms - pathology Trans-Activators - analysis Trans-Activators - genetics Trans-Activators - physiology Transcription Factors - metabolism Zinc Finger Protein GLI1 |
| title | Hedgehog signaling pathway is a possible therapeutic target for gastric cancer |
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