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Effect of 22-Oxa-1, 25-Dihydroxyvitamin D3 on Human Thyroid Cancer Cell Growth
To examine whether synthetic vitamin D3 analog, 22-oxa-1, 25(OH)2D3 (OCT) has an inhibitory effect on the growth of thyroid carcinoma, we tested the in vitro and in vivo effects of OCT on the growth of a well- differentiated thyroid cancer cell line, NPA. OCT bound to its receptor at the same rate a...
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| Published in: | ENDOCRINE JOURNAL 1999, Vol.46(2), pp.243-252 |
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| container_title | ENDOCRINE JOURNAL |
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| creator | OKANO, KUNIHIKO USA, TOSHIRO OHTSURU, AURA TSUKAZAKI, TOMOO MIYAZAKI, YOUICHI YONEKURA, AKIHIKO NAMBA, HIROYUKI SHINDOH, HIROYUKI YAMASHITA, SHUNICHI |
| description | To examine whether synthetic vitamin D3 analog, 22-oxa-1, 25(OH)2D3 (OCT) has an inhibitory effect on the growth of thyroid carcinoma, we tested the in vitro and in vivo effects of OCT on the growth of a well- differentiated thyroid cancer cell line, NPA. OCT bound to its receptor at the same rate as 1, 25(OH)2D3, and inhibited the proliferation of NPA cells in vitro in a dose-dependent manner, similar to that observed with 1, 25 (OH)2D3. Northern blot analysis showed that steady-state and fetal bovine serum-stimulated levels of c-myc mRNA were suppressed after 0.5-4 hour treatment with OCT. Transfection studies with the deletion mutants of the 5''- up-stream flanking region of c-myc/chroramphenicol acetyltransferase chimera genes indicated the presence of an OCT responsive element between -410 and -106. Next, we examined OCT effects in implanted NPA tumor cells in nude mice. OCT showed no remarkable hypercalcemic effect compared to 1, 25(OH2)D3, but OCT and 1, 25 (OH2)D3, had no significant inhibitory effect in vivo after either intra-tumor or intra-peritoneum injection. Our results demonstrate that OCT inhibits the proliferation of well-differentiated thyroid cancer in an in vitro system associated with the suppression of c-myc mRNA, but this inhibitory effect was not reproducible in in vivo model. |
| doi_str_mv | 10.1507/endocrj.46.243 |
| format | article |
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OCT bound to its receptor at the same rate as 1, 25(OH)2D3, and inhibited the proliferation of NPA cells in vitro in a dose-dependent manner, similar to that observed with 1, 25 (OH)2D3. Northern blot analysis showed that steady-state and fetal bovine serum-stimulated levels of c-myc mRNA were suppressed after 0.5-4 hour treatment with OCT. Transfection studies with the deletion mutants of the 5''- up-stream flanking region of c-myc/chroramphenicol acetyltransferase chimera genes indicated the presence of an OCT responsive element between -410 and -106. Next, we examined OCT effects in implanted NPA tumor cells in nude mice. OCT showed no remarkable hypercalcemic effect compared to 1, 25(OH2)D3, but OCT and 1, 25 (OH2)D3, had no significant inhibitory effect in vivo after either intra-tumor or intra-peritoneum injection. Our results demonstrate that OCT inhibits the proliferation of well-differentiated thyroid cancer in an in vitro system associated with the suppression of c-myc mRNA, but this inhibitory effect was not reproducible in in vivo model.</description><identifier>ISSN: 0918-8959</identifier><identifier>EISSN: 1348-4540</identifier><identifier>DOI: 10.1507/endocrj.46.243</identifier><identifier>PMID: 10460008</identifier><language>eng ; jpn</language><publisher>Japan: The Japan Endocrine Society</publisher><subject>22-oxa-1,25-dihydroxyvitamin D3(OCT) ; Animals ; Antineoplastic Agents - pharmacology ; Blotting, Northern ; c-myc gene ; Calcitriol - analogs & derivatives ; Calcitriol - pharmacology ; Carcinoma, Papillary - genetics ; Carcinoma, Papillary - metabolism ; Carcinoma, Papillary - pathology ; Cell Count - drug effects ; Cell Division - drug effects ; Cell Survival - drug effects ; DNA - biosynthesis ; Genes, myc ; Hormone therapy ; Humans ; Mice ; Mice, Nude ; Receptors, Calcitriol - metabolism ; Thyroid cancer cell ; Thyroid Neoplasms - genetics ; Thyroid Neoplasms - metabolism ; Thyroid Neoplasms - pathology ; Transfection ; Tumor Cells, Cultured ; Vitamin D3</subject><ispartof>Endocrine Journal, 1999, Vol.46(2), pp.243-252</ispartof><rights>The Japan Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5093-8544bc840875fb0eaca25cbf8597f62a36d2d932b4f9fffaa0fb5529c762867c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,1894,4043,27956,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10460008$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>OKANO, KUNIHIKO</creatorcontrib><creatorcontrib>USA, TOSHIRO</creatorcontrib><creatorcontrib>OHTSURU, AURA</creatorcontrib><creatorcontrib>TSUKAZAKI, TOMOO</creatorcontrib><creatorcontrib>MIYAZAKI, YOUICHI</creatorcontrib><creatorcontrib>YONEKURA, AKIHIKO</creatorcontrib><creatorcontrib>NAMBA, HIROYUKI</creatorcontrib><creatorcontrib>SHINDOH, HIROYUKI</creatorcontrib><creatorcontrib>YAMASHITA, SHUNICHI</creatorcontrib><creatorcontrib>Department of Orthopaedic Surgery</creatorcontrib><creatorcontrib>Nagasaki University School of Medicine</creatorcontrib><creatorcontrib>Department of Nature Medicine</creatorcontrib><creatorcontrib>Atomic Bomb Disease Institute</creatorcontrib><title>Effect of 22-Oxa-1, 25-Dihydroxyvitamin D3 on Human Thyroid Cancer Cell Growth</title><title>ENDOCRINE JOURNAL</title><addtitle>Endocr J</addtitle><description>To examine whether synthetic vitamin D3 analog, 22-oxa-1, 25(OH)2D3 (OCT) has an inhibitory effect on the growth of thyroid carcinoma, we tested the in vitro and in vivo effects of OCT on the growth of a well- differentiated thyroid cancer cell line, NPA. OCT bound to its receptor at the same rate as 1, 25(OH)2D3, and inhibited the proliferation of NPA cells in vitro in a dose-dependent manner, similar to that observed with 1, 25 (OH)2D3. Northern blot analysis showed that steady-state and fetal bovine serum-stimulated levels of c-myc mRNA were suppressed after 0.5-4 hour treatment with OCT. Transfection studies with the deletion mutants of the 5''- up-stream flanking region of c-myc/chroramphenicol acetyltransferase chimera genes indicated the presence of an OCT responsive element between -410 and -106. Next, we examined OCT effects in implanted NPA tumor cells in nude mice. OCT showed no remarkable hypercalcemic effect compared to 1, 25(OH2)D3, but OCT and 1, 25 (OH2)D3, had no significant inhibitory effect in vivo after either intra-tumor or intra-peritoneum injection. Our results demonstrate that OCT inhibits the proliferation of well-differentiated thyroid cancer in an in vitro system associated with the suppression of c-myc mRNA, but this inhibitory effect was not reproducible in in vivo model.</description><subject>22-oxa-1,25-dihydroxyvitamin D3(OCT)</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Blotting, Northern</subject><subject>c-myc gene</subject><subject>Calcitriol - analogs & derivatives</subject><subject>Calcitriol - pharmacology</subject><subject>Carcinoma, Papillary - genetics</subject><subject>Carcinoma, Papillary - metabolism</subject><subject>Carcinoma, Papillary - pathology</subject><subject>Cell Count - drug effects</subject><subject>Cell Division - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>DNA - biosynthesis</subject><subject>Genes, myc</subject><subject>Hormone therapy</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Receptors, Calcitriol - metabolism</subject><subject>Thyroid cancer cell</subject><subject>Thyroid Neoplasms - genetics</subject><subject>Thyroid Neoplasms - metabolism</subject><subject>Thyroid Neoplasms - pathology</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><subject>Vitamin D3</subject><issn>0918-8959</issn><issn>1348-4540</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><recordid>eNpNkMtOwzAQRS0EgvLYskT-AFLGz9hLVKAgIdjA2nIcm6ZKY3BSoH-PSwCxmJmF7z2euQidEpgSAeWF7-ro0nLK5ZRytoMmhHFVcMFhF01AE1UoLfQBOuz7JQBjgrN9dECASwBQE_RwHYJ3A44BU1o8ftqCnGMqiqtmsalT_Ny8N4NdNR2-Yjh2-Ha9sh1-WmxSbGo8s53zCc982-J5ih_D4hjtBdv2_uRnHqHnm-un2W1x_zi_m13eF06AZoUSnFdOcVClCBV46ywVrgpK6DJIapmsaa0ZrXjQIQRrIVRCUO1KSZUsHTtC05HrUuz75IN5Tc3Kpo0hYLbBmJ9gDJcmB5MNZ6PhdV2tfP1PPiaRBTejIL82zraxa5vOm2Vcpy5fYtyb_EYaorU2sLXRPHJlfG6CUtBSkgyaj6BlP9gX__eTTUPjWv-7WMaw7-XGtoX8KtzCpixjX4BOjZ4</recordid><startdate>1999</startdate><enddate>1999</enddate><creator>OKANO, KUNIHIKO</creator><creator>USA, TOSHIRO</creator><creator>OHTSURU, AURA</creator><creator>TSUKAZAKI, TOMOO</creator><creator>MIYAZAKI, YOUICHI</creator><creator>YONEKURA, AKIHIKO</creator><creator>NAMBA, HIROYUKI</creator><creator>SHINDOH, HIROYUKI</creator><creator>YAMASHITA, SHUNICHI</creator><general>The Japan Endocrine Society</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></search><sort><creationdate>1999</creationdate><title>Effect of 22-Oxa-1, 25-Dihydroxyvitamin D3 on Human Thyroid Cancer Cell Growth</title><author>OKANO, KUNIHIKO ; USA, TOSHIRO ; OHTSURU, AURA ; TSUKAZAKI, TOMOO ; MIYAZAKI, YOUICHI ; YONEKURA, AKIHIKO ; NAMBA, HIROYUKI ; SHINDOH, HIROYUKI ; YAMASHITA, SHUNICHI</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5093-8544bc840875fb0eaca25cbf8597f62a36d2d932b4f9fffaa0fb5529c762867c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng ; jpn</language><creationdate>1999</creationdate><topic>22-oxa-1,25-dihydroxyvitamin D3(OCT)</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Blotting, Northern</topic><topic>c-myc gene</topic><topic>Calcitriol - analogs & derivatives</topic><topic>Calcitriol - pharmacology</topic><topic>Carcinoma, Papillary - genetics</topic><topic>Carcinoma, Papillary - metabolism</topic><topic>Carcinoma, Papillary - pathology</topic><topic>Cell Count - drug effects</topic><topic>Cell Division - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>DNA - biosynthesis</topic><topic>Genes, myc</topic><topic>Hormone therapy</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Receptors, Calcitriol - metabolism</topic><topic>Thyroid cancer cell</topic><topic>Thyroid Neoplasms - genetics</topic><topic>Thyroid Neoplasms - metabolism</topic><topic>Thyroid Neoplasms - pathology</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><topic>Vitamin D3</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>OKANO, KUNIHIKO</creatorcontrib><creatorcontrib>USA, TOSHIRO</creatorcontrib><creatorcontrib>OHTSURU, AURA</creatorcontrib><creatorcontrib>TSUKAZAKI, TOMOO</creatorcontrib><creatorcontrib>MIYAZAKI, YOUICHI</creatorcontrib><creatorcontrib>YONEKURA, AKIHIKO</creatorcontrib><creatorcontrib>NAMBA, HIROYUKI</creatorcontrib><creatorcontrib>SHINDOH, HIROYUKI</creatorcontrib><creatorcontrib>YAMASHITA, SHUNICHI</creatorcontrib><creatorcontrib>Department of Orthopaedic Surgery</creatorcontrib><creatorcontrib>Nagasaki University School of Medicine</creatorcontrib><creatorcontrib>Department of Nature Medicine</creatorcontrib><creatorcontrib>Atomic Bomb Disease Institute</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>ENDOCRINE JOURNAL</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>OKANO, KUNIHIKO</au><au>USA, TOSHIRO</au><au>OHTSURU, AURA</au><au>TSUKAZAKI, TOMOO</au><au>MIYAZAKI, YOUICHI</au><au>YONEKURA, AKIHIKO</au><au>NAMBA, HIROYUKI</au><au>SHINDOH, HIROYUKI</au><au>YAMASHITA, SHUNICHI</au><aucorp>Department of Orthopaedic Surgery</aucorp><aucorp>Nagasaki University School of Medicine</aucorp><aucorp>Department of Nature Medicine</aucorp><aucorp>Atomic Bomb Disease Institute</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of 22-Oxa-1, 25-Dihydroxyvitamin D3 on Human Thyroid Cancer Cell Growth</atitle><jtitle>ENDOCRINE JOURNAL</jtitle><addtitle>Endocr J</addtitle><date>1999</date><risdate>1999</risdate><volume>46</volume><issue>2</issue><spage>243</spage><epage>252</epage><pages>243-252</pages><issn>0918-8959</issn><eissn>1348-4540</eissn><abstract>To examine whether synthetic vitamin D3 analog, 22-oxa-1, 25(OH)2D3 (OCT) has an inhibitory effect on the growth of thyroid carcinoma, we tested the in vitro and in vivo effects of OCT on the growth of a well- differentiated thyroid cancer cell line, NPA. OCT bound to its receptor at the same rate as 1, 25(OH)2D3, and inhibited the proliferation of NPA cells in vitro in a dose-dependent manner, similar to that observed with 1, 25 (OH)2D3. Northern blot analysis showed that steady-state and fetal bovine serum-stimulated levels of c-myc mRNA were suppressed after 0.5-4 hour treatment with OCT. Transfection studies with the deletion mutants of the 5''- up-stream flanking region of c-myc/chroramphenicol acetyltransferase chimera genes indicated the presence of an OCT responsive element between -410 and -106. Next, we examined OCT effects in implanted NPA tumor cells in nude mice. OCT showed no remarkable hypercalcemic effect compared to 1, 25(OH2)D3, but OCT and 1, 25 (OH2)D3, had no significant inhibitory effect in vivo after either intra-tumor or intra-peritoneum injection. Our results demonstrate that OCT inhibits the proliferation of well-differentiated thyroid cancer in an in vitro system associated with the suppression of c-myc mRNA, but this inhibitory effect was not reproducible in in vivo model.</abstract><cop>Japan</cop><pub>The Japan Endocrine Society</pub><pmid>10460008</pmid><doi>10.1507/endocrj.46.243</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0918-8959 |
| ispartof | Endocrine Journal, 1999, Vol.46(2), pp.243-252 |
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| language | eng ; jpn |
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| source | J-STAGE (Japan Science & Tech Info) Free |
| subjects | 22-oxa-1,25-dihydroxyvitamin D3(OCT) Animals Antineoplastic Agents - pharmacology Blotting, Northern c-myc gene Calcitriol - analogs & derivatives Calcitriol - pharmacology Carcinoma, Papillary - genetics Carcinoma, Papillary - metabolism Carcinoma, Papillary - pathology Cell Count - drug effects Cell Division - drug effects Cell Survival - drug effects DNA - biosynthesis Genes, myc Hormone therapy Humans Mice Mice, Nude Receptors, Calcitriol - metabolism Thyroid cancer cell Thyroid Neoplasms - genetics Thyroid Neoplasms - metabolism Thyroid Neoplasms - pathology Transfection Tumor Cells, Cultured Vitamin D3 |
| title | Effect of 22-Oxa-1, 25-Dihydroxyvitamin D3 on Human Thyroid Cancer Cell Growth |
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