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Intravenous Cereport (RMP-7) enhances delivery of hydrophilic chemotherapeutics and increases survival in rats with metastatic tumors in the brain
The following experiments determined whether intravenous infusions of Cereport enhance delivery of chemotherapeutics and prolong survival in rats with metastatic tumors in the brain. Autoradiography and scintillation were used to examine uptake of the lipophilic (paclitaxel and carmustine) and the h...
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| Published in: | Pharmaceutical research 2000-10, Vol.17 (10), p.1212-1219 |
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| container_title | Pharmaceutical research |
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| creator | EMERICH, Dwaine F DEAN, Reginald L MARSH, Joanne PINK, Melissa LAFRENIERE, Denise SNODGRASS, Pamela BARTUS, Raymond T |
| description | The following experiments determined whether intravenous infusions of Cereport enhance delivery of chemotherapeutics and prolong survival in rats with metastatic tumors in the brain.
Autoradiography and scintillation were used to examine uptake of the lipophilic (paclitaxel and carmustine) and the hydrophilic (carboplatin) chemotherapeutic agents, as well as the large hydrophilic marker, 70 kDa dextran. Cereport was also tested in combination with the chemotherapeutic drugs carboplatin, vinorelbine, gemcitabine and carmustine to determine if Cereport could enhance the survival benefit beyond that provided by chemotherapy alone.
Cereport enhanced the uptake of carboplatin and dextran, but not paclitaxel or carmustine. The pattern of Cereport's uptake effect with carboplatin revealed that Cereport selectively increased the proportion of highly permeable regions. Survival was significantly enhanced when Cereport was combined with either carboplatin, vinorelbine, or gemcitabine, but not carmustine, compared to each chemotherapeutic agent alone.
These data provide the first evidence that Cereport, or any receptor-mediated approach intended to enhance the permeability of the blood-brain tumor barrier, can increase the delivery hydrophilic drugs to metastatic tumors in the brain, increasing survival in tumor-bearing rats. |
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Autoradiography and scintillation were used to examine uptake of the lipophilic (paclitaxel and carmustine) and the hydrophilic (carboplatin) chemotherapeutic agents, as well as the large hydrophilic marker, 70 kDa dextran. Cereport was also tested in combination with the chemotherapeutic drugs carboplatin, vinorelbine, gemcitabine and carmustine to determine if Cereport could enhance the survival benefit beyond that provided by chemotherapy alone.
Cereport enhanced the uptake of carboplatin and dextran, but not paclitaxel or carmustine. The pattern of Cereport's uptake effect with carboplatin revealed that Cereport selectively increased the proportion of highly permeable regions. Survival was significantly enhanced when Cereport was combined with either carboplatin, vinorelbine, or gemcitabine, but not carmustine, compared to each chemotherapeutic agent alone.
These data provide the first evidence that Cereport, or any receptor-mediated approach intended to enhance the permeability of the blood-brain tumor barrier, can increase the delivery hydrophilic drugs to metastatic tumors in the brain, increasing survival in tumor-bearing rats.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>PMID: 11145226</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Animals ; Antineoplastic agents ; Antineoplastic Agents - pharmacokinetics ; Antineoplastic Agents - pharmacology ; Autoradiography ; Biological and medical sciences ; Blood-Brain Barrier - drug effects ; Bradykinin - analogs & derivatives ; Bradykinin - pharmacology ; Brain - metabolism ; Brain cancer ; Brain Neoplasms - drug therapy ; Brain Neoplasms - metabolism ; Brain Neoplasms - secondary ; Carboplatin - pharmacokinetics ; Carboplatin - pharmacology ; Carmustine - pharmacokinetics ; Carmustine - pharmacology ; Chemotherapy ; Deoxycytidine - analogs & derivatives ; Deoxycytidine - pharmacokinetics ; Deoxycytidine - pharmacology ; Drugs ; Effectiveness ; Male ; Medical sciences ; Metastasis ; Permeability ; Pharmacology. Drug treatments ; Rats ; Rats, Inbred F344 ; Tumors ; Vinblastine - analogs & derivatives ; Vinblastine - pharmacokinetics ; Vinblastine - pharmacology ; Vinorelbine</subject><ispartof>Pharmaceutical research, 2000-10, Vol.17 (10), p.1212-1219</ispartof><rights>2001 INIST-CNRS</rights><rights>Copyright Kluwer Academic Publishers Oct 2000</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=832153$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11145226$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>EMERICH, Dwaine F</creatorcontrib><creatorcontrib>DEAN, Reginald L</creatorcontrib><creatorcontrib>MARSH, Joanne</creatorcontrib><creatorcontrib>PINK, Melissa</creatorcontrib><creatorcontrib>LAFRENIERE, Denise</creatorcontrib><creatorcontrib>SNODGRASS, Pamela</creatorcontrib><creatorcontrib>BARTUS, Raymond T</creatorcontrib><title>Intravenous Cereport (RMP-7) enhances delivery of hydrophilic chemotherapeutics and increases survival in rats with metastatic tumors in the brain</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>The following experiments determined whether intravenous infusions of Cereport enhance delivery of chemotherapeutics and prolong survival in rats with metastatic tumors in the brain.
Autoradiography and scintillation were used to examine uptake of the lipophilic (paclitaxel and carmustine) and the hydrophilic (carboplatin) chemotherapeutic agents, as well as the large hydrophilic marker, 70 kDa dextran. Cereport was also tested in combination with the chemotherapeutic drugs carboplatin, vinorelbine, gemcitabine and carmustine to determine if Cereport could enhance the survival benefit beyond that provided by chemotherapy alone.
Cereport enhanced the uptake of carboplatin and dextran, but not paclitaxel or carmustine. The pattern of Cereport's uptake effect with carboplatin revealed that Cereport selectively increased the proportion of highly permeable regions. Survival was significantly enhanced when Cereport was combined with either carboplatin, vinorelbine, or gemcitabine, but not carmustine, compared to each chemotherapeutic agent alone.
These data provide the first evidence that Cereport, or any receptor-mediated approach intended to enhance the permeability of the blood-brain tumor barrier, can increase the delivery hydrophilic drugs to metastatic tumors in the brain, increasing survival in tumor-bearing rats.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Autoradiography</subject><subject>Biological and medical sciences</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>Bradykinin - analogs & derivatives</subject><subject>Bradykinin - pharmacology</subject><subject>Brain - metabolism</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain Neoplasms - secondary</subject><subject>Carboplatin - pharmacokinetics</subject><subject>Carboplatin - pharmacology</subject><subject>Carmustine - pharmacokinetics</subject><subject>Carmustine - pharmacology</subject><subject>Chemotherapy</subject><subject>Deoxycytidine - analogs & derivatives</subject><subject>Deoxycytidine - pharmacokinetics</subject><subject>Deoxycytidine - pharmacology</subject><subject>Drugs</subject><subject>Effectiveness</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metastasis</subject><subject>Permeability</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Tumors</subject><subject>Vinblastine - analogs & derivatives</subject><subject>Vinblastine - pharmacokinetics</subject><subject>Vinblastine - pharmacology</subject><subject>Vinorelbine</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><recordid>eNpd0M1q3DAQB3ATGrKbj1cIooWSHgz6smwfw9I2gZSGkEBuZiSPsRZbdiR5y75GnjgK2fbQ08DMb4bhf5StWVGKvKby-VO2piWXeVVKtspOQ9hSSitWy5NsxRiTBedqnb3euuhhh25aAtmgx3nykVw9_LrPy28EXQ_OYCAtDnaHfk-mjvT71k9zbwdriOlxnGKPHmZcojWBgGuJdcYjhLQXFr-zOxhSi3iIgfyxsScjRggRkidxGScf3sfpCtEerDvPjjsYAl4c6ln29OP74-Ymv_v983ZzfZfPjNYq1yVwSYVQQnPTKtlRqZipGK8YUK1ooTuhaiU4yoLWgmqua8UKLLXseCe5OMu-ftyd_fSyYIjNaIPBYQCHKY2m5AUrFaUJfv4PbqfFu_Rbw1OIleSsTujygBY9YtvM3o7g983fqBP4cgAQDAydT8na8M9VgrNCiDe8wYix</recordid><startdate>200010</startdate><enddate>200010</enddate><creator>EMERICH, Dwaine F</creator><creator>DEAN, Reginald L</creator><creator>MARSH, Joanne</creator><creator>PINK, Melissa</creator><creator>LAFRENIERE, Denise</creator><creator>SNODGRASS, Pamela</creator><creator>BARTUS, Raymond T</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>200010</creationdate><title>Intravenous Cereport (RMP-7) enhances delivery of hydrophilic chemotherapeutics and increases survival in rats with metastatic tumors in the brain</title><author>EMERICH, Dwaine F ; DEAN, Reginald L ; MARSH, Joanne ; PINK, Melissa ; LAFRENIERE, Denise ; SNODGRASS, Pamela ; BARTUS, Raymond T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p1096-b7a2403363b2cd64f0461c81281a0b605bf369632e450930b2b9615e7b4f2f423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Autoradiography</topic><topic>Biological and medical sciences</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Bradykinin - analogs & derivatives</topic><topic>Bradykinin - pharmacology</topic><topic>Brain - metabolism</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - drug therapy</topic><topic>Brain Neoplasms - metabolism</topic><topic>Brain Neoplasms - secondary</topic><topic>Carboplatin - pharmacokinetics</topic><topic>Carboplatin - pharmacology</topic><topic>Carmustine - pharmacokinetics</topic><topic>Carmustine - pharmacology</topic><topic>Chemotherapy</topic><topic>Deoxycytidine - analogs & derivatives</topic><topic>Deoxycytidine - pharmacokinetics</topic><topic>Deoxycytidine - pharmacology</topic><topic>Drugs</topic><topic>Effectiveness</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metastasis</topic><topic>Permeability</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Tumors</topic><topic>Vinblastine - analogs & derivatives</topic><topic>Vinblastine - pharmacokinetics</topic><topic>Vinblastine - pharmacology</topic><topic>Vinorelbine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>EMERICH, Dwaine F</creatorcontrib><creatorcontrib>DEAN, Reginald L</creatorcontrib><creatorcontrib>MARSH, Joanne</creatorcontrib><creatorcontrib>PINK, Melissa</creatorcontrib><creatorcontrib>LAFRENIERE, Denise</creatorcontrib><creatorcontrib>SNODGRASS, Pamela</creatorcontrib><creatorcontrib>BARTUS, Raymond T</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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database (ProQuest)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma 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)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Nursing & Allied Health Premium</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>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>EMERICH, Dwaine F</au><au>DEAN, Reginald L</au><au>MARSH, Joanne</au><au>PINK, Melissa</au><au>LAFRENIERE, Denise</au><au>SNODGRASS, Pamela</au><au>BARTUS, Raymond T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intravenous Cereport (RMP-7) enhances delivery of hydrophilic chemotherapeutics and increases survival in rats with metastatic tumors in the brain</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>2000-10</date><risdate>2000</risdate><volume>17</volume><issue>10</issue><spage>1212</spage><epage>1219</epage><pages>1212-1219</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>The following experiments determined whether intravenous infusions of Cereport enhance delivery of chemotherapeutics and prolong survival in rats with metastatic tumors in the brain.
Autoradiography and scintillation were used to examine uptake of the lipophilic (paclitaxel and carmustine) and the hydrophilic (carboplatin) chemotherapeutic agents, as well as the large hydrophilic marker, 70 kDa dextran. Cereport was also tested in combination with the chemotherapeutic drugs carboplatin, vinorelbine, gemcitabine and carmustine to determine if Cereport could enhance the survival benefit beyond that provided by chemotherapy alone.
Cereport enhanced the uptake of carboplatin and dextran, but not paclitaxel or carmustine. The pattern of Cereport's uptake effect with carboplatin revealed that Cereport selectively increased the proportion of highly permeable regions. Survival was significantly enhanced when Cereport was combined with either carboplatin, vinorelbine, or gemcitabine, but not carmustine, compared to each chemotherapeutic agent alone.
These data provide the first evidence that Cereport, or any receptor-mediated approach intended to enhance the permeability of the blood-brain tumor barrier, can increase the delivery hydrophilic drugs to metastatic tumors in the brain, increasing survival in tumor-bearing rats.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>11145226</pmid><tpages>8</tpages></addata></record> |
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| subjects | Animals Antineoplastic agents Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - pharmacology Autoradiography Biological and medical sciences Blood-Brain Barrier - drug effects Bradykinin - analogs & derivatives Bradykinin - pharmacology Brain - metabolism Brain cancer Brain Neoplasms - drug therapy Brain Neoplasms - metabolism Brain Neoplasms - secondary Carboplatin - pharmacokinetics Carboplatin - pharmacology Carmustine - pharmacokinetics Carmustine - pharmacology Chemotherapy Deoxycytidine - analogs & derivatives Deoxycytidine - pharmacokinetics Deoxycytidine - pharmacology Drugs Effectiveness Male Medical sciences Metastasis Permeability Pharmacology. Drug treatments Rats Rats, Inbred F344 Tumors Vinblastine - analogs & derivatives Vinblastine - pharmacokinetics Vinblastine - pharmacology Vinorelbine |
| title | Intravenous Cereport (RMP-7) enhances delivery of hydrophilic chemotherapeutics and increases survival in rats with metastatic tumors in the brain |
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