Inhibitory effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 on the growth of the androgen-independent dunning R-3327-AT-1 rat prostate cancer
The effects of somatostatin analogue RC-160 and bombesin/gastrin releasing-peptide (GRP) antagonist RC-3095 were evaluated in Copenhagen rats bearing the anaplastic, androgen-independent Dunning R3327-AT-1 prostatic adenocarcinoma. In the first experiment, RC-160 was given in the form of microcapsul...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 1994, Vol.54 (1), p.169-174 |
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| description | The effects of somatostatin analogue RC-160 and bombesin/gastrin releasing-peptide (GRP) antagonist RC-3095 were evaluated in Copenhagen rats bearing the anaplastic, androgen-independent Dunning R3327-AT-1 prostatic adenocarcinoma. In the first experiment, RC-160 was given in the form of microcapsules releasing 60 micrograms/day/rat. RC-3095 was administered from implanted Alzet osmotic minipumps liberating 100 micrograms/day/rat. After 32 days, tumor volumes and weights were significantly reduced by RC-160 as compared with the control group. Tumor doubling time in rats treated with RC-160 was significantly longer than in controls. Bombesin/GRP antagonist RC-3095 also significantly reduced tumor volume after 7 days of treatment, but after 18 days the inhibition in tumor volume was no longer significant. Tumor growth was not suppressed by castration. In the second experiment, 3-mm3 fragments of Dunning R-3327-AT-1 tumor were implanted orthotopically into the prostates of Copenhagen rats in order to evaluate the survival time of animals bearing this cancer during treatment with RC-160 released from Alzet osmotic minipumps at a dose of 100 micrograms/day/rat. Treatment with RC-160 significantly (P < 0.05) prolonged the mean survival time of rats by 5.3 days as compared to control animals. In both experiments, therapy with RC-160 significantly decreased serum growth hormone or insulin-like growth factor I levels. In the first experiment, receptor assays on R-3327-AT-1 tumor membranes showed high affinity binding sites for somatostatin, bombesin, and epidermal growth factor. At the end of the treatment, receptors for epidermal growth factor were significantly down-regulated by treatment with RC-160 but not with RC-3095. The binding capacity of bombesin receptors was reduced to nondetectable levels after the treatment with RC-3095. In cell cultures, high affinity binding sites for bombesin/GRP were found on intact Dunning R-3327-AT-1 cells, but receptors for somatostatin could not be detected. Proliferation of the AT-1 cell line was significantly inhibited by antagonist RC-3095. However, no effect on tumor cell growth in vitro was observed with analogue RC-160. Our results demonstrate that somatostatin analogue RC-160 and bombesin/GRP antagonist RC-3095 can inhibit the growth of the androgen-independent Dunning R-3327-AT-1 prostatic cancer in rats, although the remission produced by RC-3095 may be of short duration due to a down-regulation of bombesin receptors. |
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V</creator><creatorcontrib>PINSKI, J ; REILE, H ; HALMOS, G ; GROOT, K ; SCHALLY, A. V</creatorcontrib><description>The effects of somatostatin analogue RC-160 and bombesin/gastrin releasing-peptide (GRP) antagonist RC-3095 were evaluated in Copenhagen rats bearing the anaplastic, androgen-independent Dunning R3327-AT-1 prostatic adenocarcinoma. In the first experiment, RC-160 was given in the form of microcapsules releasing 60 micrograms/day/rat. RC-3095 was administered from implanted Alzet osmotic minipumps liberating 100 micrograms/day/rat. After 32 days, tumor volumes and weights were significantly reduced by RC-160 as compared with the control group. Tumor doubling time in rats treated with RC-160 was significantly longer than in controls. Bombesin/GRP antagonist RC-3095 also significantly reduced tumor volume after 7 days of treatment, but after 18 days the inhibition in tumor volume was no longer significant. Tumor growth was not suppressed by castration. In the second experiment, 3-mm3 fragments of Dunning R-3327-AT-1 tumor were implanted orthotopically into the prostates of Copenhagen rats in order to evaluate the survival time of animals bearing this cancer during treatment with RC-160 released from Alzet osmotic minipumps at a dose of 100 micrograms/day/rat. Treatment with RC-160 significantly (P < 0.05) prolonged the mean survival time of rats by 5.3 days as compared to control animals. In both experiments, therapy with RC-160 significantly decreased serum growth hormone or insulin-like growth factor I levels. In the first experiment, receptor assays on R-3327-AT-1 tumor membranes showed high affinity binding sites for somatostatin, bombesin, and epidermal growth factor. At the end of the treatment, receptors for epidermal growth factor were significantly down-regulated by treatment with RC-160 but not with RC-3095. The binding capacity of bombesin receptors was reduced to nondetectable levels after the treatment with RC-3095. In cell cultures, high affinity binding sites for bombesin/GRP were found on intact Dunning R-3327-AT-1 cells, but receptors for somatostatin could not be detected. Proliferation of the AT-1 cell line was significantly inhibited by antagonist RC-3095. However, no effect on tumor cell growth in vitro was observed with analogue RC-160. Our results demonstrate that somatostatin analogue RC-160 and bombesin/GRP antagonist RC-3095 can inhibit the growth of the androgen-independent Dunning R-3327-AT-1 prostatic cancer in rats, although the remission produced by RC-3095 may be of short duration due to a down-regulation of bombesin receptors. Our work suggests the merit of further investigation as to whether these analogues can induce a possible delay in relapse and prolong survival in prostate cancer.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 7903203</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Amino Acid Sequence ; Animals ; Antineoplastic agents ; Antineoplastic Agents - pharmacology ; Biological and medical sciences ; Bombesin - analogs & derivatives ; Bombesin - pharmacology ; Castration ; Cell Division - drug effects ; Chemotherapy ; Drug Screening Assays, Antitumor ; Gastrins - blood ; Growth Hormone - blood ; Male ; Medical sciences ; Molecular Sequence Data ; Neoplasm Transplantation ; Peptide Fragments - pharmacology ; Pharmacology. Drug treatments ; Prostatic Neoplasms - blood ; Prostatic Neoplasms - drug therapy ; Prostatic Neoplasms - pathology ; Rats ; Receptor, Epidermal Growth Factor - metabolism ; Somatostatin - analogs & derivatives ; Somatostatin - pharmacology</subject><ispartof>Cancer research (Chicago, Ill.), 1994, Vol.54 (1), p.169-174</ispartof><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3879407$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7903203$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PINSKI, J</creatorcontrib><creatorcontrib>REILE, H</creatorcontrib><creatorcontrib>HALMOS, G</creatorcontrib><creatorcontrib>GROOT, K</creatorcontrib><creatorcontrib>SCHALLY, A. V</creatorcontrib><title>Inhibitory effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 on the growth of the androgen-independent dunning R-3327-AT-1 rat prostate cancer</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>The effects of somatostatin analogue RC-160 and bombesin/gastrin releasing-peptide (GRP) antagonist RC-3095 were evaluated in Copenhagen rats bearing the anaplastic, androgen-independent Dunning R3327-AT-1 prostatic adenocarcinoma. In the first experiment, RC-160 was given in the form of microcapsules releasing 60 micrograms/day/rat. RC-3095 was administered from implanted Alzet osmotic minipumps liberating 100 micrograms/day/rat. After 32 days, tumor volumes and weights were significantly reduced by RC-160 as compared with the control group. Tumor doubling time in rats treated with RC-160 was significantly longer than in controls. Bombesin/GRP antagonist RC-3095 also significantly reduced tumor volume after 7 days of treatment, but after 18 days the inhibition in tumor volume was no longer significant. Tumor growth was not suppressed by castration. In the second experiment, 3-mm3 fragments of Dunning R-3327-AT-1 tumor were implanted orthotopically into the prostates of Copenhagen rats in order to evaluate the survival time of animals bearing this cancer during treatment with RC-160 released from Alzet osmotic minipumps at a dose of 100 micrograms/day/rat. Treatment with RC-160 significantly (P < 0.05) prolonged the mean survival time of rats by 5.3 days as compared to control animals. In both experiments, therapy with RC-160 significantly decreased serum growth hormone or insulin-like growth factor I levels. In the first experiment, receptor assays on R-3327-AT-1 tumor membranes showed high affinity binding sites for somatostatin, bombesin, and epidermal growth factor. At the end of the treatment, receptors for epidermal growth factor were significantly down-regulated by treatment with RC-160 but not with RC-3095. The binding capacity of bombesin receptors was reduced to nondetectable levels after the treatment with RC-3095. In cell cultures, high affinity binding sites for bombesin/GRP were found on intact Dunning R-3327-AT-1 cells, but receptors for somatostatin could not be detected. Proliferation of the AT-1 cell line was significantly inhibited by antagonist RC-3095. However, no effect on tumor cell growth in vitro was observed with analogue RC-160. Our results demonstrate that somatostatin analogue RC-160 and bombesin/GRP antagonist RC-3095 can inhibit the growth of the androgen-independent Dunning R-3327-AT-1 prostatic cancer in rats, although the remission produced by RC-3095 may be of short duration due to a down-regulation of bombesin receptors. Our work suggests the merit of further investigation as to whether these analogues can induce a possible delay in relapse and prolong survival in prostate cancer.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Bombesin - analogs & derivatives</subject><subject>Bombesin - pharmacology</subject><subject>Castration</subject><subject>Cell Division - drug effects</subject><subject>Chemotherapy</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Gastrins - blood</subject><subject>Growth Hormone - blood</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Neoplasm Transplantation</subject><subject>Peptide Fragments - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Prostatic Neoplasms - blood</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Rats</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Somatostatin - analogs & derivatives</subject><subject>Somatostatin - pharmacology</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9UE1r3DAQNSEl2ab9CQEdQm6i-rAs-xiWpA0sFMLel5E19irYkiPJlPy5_LZo26WXGd7Mm_dm5qLacCVbqutaXVYbxlhLVa3FdfU1pdcCFWfqqrrSHZOCyU318eyPzrgc4jvBYcA-JxIGksIMOaQM2XkCHqYwrkhetpQ3rGBLTJgNJud_jJBydJ5GnBBKYSQLLtlZLLQMY_Au5dOgZJ0iwZN8RDLG8CcfTz4nVORiGNFT5y0uWILPxK7en8ReqJRC04c95SRCJkv8uxWSHnyP8Vv1ZYAp4fdzvqn2T4_77S-6-_3zefuwo0fR6EyFNtxwZlUnBQjewWC7FkWn27bXcpDYI_QWFDeNqYXQtpZWWAUdGC6bVt5U9_9ki_3biikfZpd6nCbwGNZ00I0ULWtEId6eiauZ0R6W6GaI74fzv0v_7tyH1MM0xHKFS_9pstVdzbT8BLjfi7M</recordid><startdate>1994</startdate><enddate>1994</enddate><creator>PINSKI, J</creator><creator>REILE, H</creator><creator>HALMOS, G</creator><creator>GROOT, K</creator><creator>SCHALLY, A. V</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>1994</creationdate><title>Inhibitory effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 on the growth of the androgen-independent dunning R-3327-AT-1 rat prostate cancer</title><author>PINSKI, J ; REILE, H ; HALMOS, G ; GROOT, K ; SCHALLY, A. V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h267t-27b1b10d5932a219afd98e29788c73f3eceacda51b6b4227d43d2d5a9ab13683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Bombesin - analogs & derivatives</topic><topic>Bombesin - pharmacology</topic><topic>Castration</topic><topic>Cell Division - drug effects</topic><topic>Chemotherapy</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Gastrins - blood</topic><topic>Growth Hormone - blood</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Neoplasm Transplantation</topic><topic>Peptide Fragments - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Prostatic Neoplasms - blood</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Rats</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Somatostatin - analogs & derivatives</topic><topic>Somatostatin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PINSKI, J</creatorcontrib><creatorcontrib>REILE, H</creatorcontrib><creatorcontrib>HALMOS, G</creatorcontrib><creatorcontrib>GROOT, K</creatorcontrib><creatorcontrib>SCHALLY, A. V</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PINSKI, J</au><au>REILE, H</au><au>HALMOS, G</au><au>GROOT, K</au><au>SCHALLY, A. V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibitory effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 on the growth of the androgen-independent dunning R-3327-AT-1 rat prostate cancer</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>1994</date><risdate>1994</risdate><volume>54</volume><issue>1</issue><spage>169</spage><epage>174</epage><pages>169-174</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>The effects of somatostatin analogue RC-160 and bombesin/gastrin releasing-peptide (GRP) antagonist RC-3095 were evaluated in Copenhagen rats bearing the anaplastic, androgen-independent Dunning R3327-AT-1 prostatic adenocarcinoma. In the first experiment, RC-160 was given in the form of microcapsules releasing 60 micrograms/day/rat. RC-3095 was administered from implanted Alzet osmotic minipumps liberating 100 micrograms/day/rat. After 32 days, tumor volumes and weights were significantly reduced by RC-160 as compared with the control group. Tumor doubling time in rats treated with RC-160 was significantly longer than in controls. Bombesin/GRP antagonist RC-3095 also significantly reduced tumor volume after 7 days of treatment, but after 18 days the inhibition in tumor volume was no longer significant. Tumor growth was not suppressed by castration. In the second experiment, 3-mm3 fragments of Dunning R-3327-AT-1 tumor were implanted orthotopically into the prostates of Copenhagen rats in order to evaluate the survival time of animals bearing this cancer during treatment with RC-160 released from Alzet osmotic minipumps at a dose of 100 micrograms/day/rat. Treatment with RC-160 significantly (P < 0.05) prolonged the mean survival time of rats by 5.3 days as compared to control animals. In both experiments, therapy with RC-160 significantly decreased serum growth hormone or insulin-like growth factor I levels. In the first experiment, receptor assays on R-3327-AT-1 tumor membranes showed high affinity binding sites for somatostatin, bombesin, and epidermal growth factor. At the end of the treatment, receptors for epidermal growth factor were significantly down-regulated by treatment with RC-160 but not with RC-3095. The binding capacity of bombesin receptors was reduced to nondetectable levels after the treatment with RC-3095. In cell cultures, high affinity binding sites for bombesin/GRP were found on intact Dunning R-3327-AT-1 cells, but receptors for somatostatin could not be detected. Proliferation of the AT-1 cell line was significantly inhibited by antagonist RC-3095. However, no effect on tumor cell growth in vitro was observed with analogue RC-160. Our results demonstrate that somatostatin analogue RC-160 and bombesin/GRP antagonist RC-3095 can inhibit the growth of the androgen-independent Dunning R-3327-AT-1 prostatic cancer in rats, although the remission produced by RC-3095 may be of short duration due to a down-regulation of bombesin receptors. Our work suggests the merit of further investigation as to whether these analogues can induce a possible delay in relapse and prolong survival in prostate cancer.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>7903203</pmid><tpages>6</tpages></addata></record> |
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| ispartof | Cancer research (Chicago, Ill.), 1994, Vol.54 (1), p.169-174 |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| subjects | Amino Acid Sequence Animals Antineoplastic agents Antineoplastic Agents - pharmacology Biological and medical sciences Bombesin - analogs & derivatives Bombesin - pharmacology Castration Cell Division - drug effects Chemotherapy Drug Screening Assays, Antitumor Gastrins - blood Growth Hormone - blood Male Medical sciences Molecular Sequence Data Neoplasm Transplantation Peptide Fragments - pharmacology Pharmacology. Drug treatments Prostatic Neoplasms - blood Prostatic Neoplasms - drug therapy Prostatic Neoplasms - pathology Rats Receptor, Epidermal Growth Factor - metabolism Somatostatin - analogs & derivatives Somatostatin - pharmacology |
| title | Inhibitory effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 on the growth of the androgen-independent dunning R-3327-AT-1 rat prostate cancer |
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