Administration of a Phorbol ester to patients with hematological malignancies: Preliminary results from a Phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate
Phorbol esters are capable of inducing a broad range of cellular effects,including the maturation/differentiation of hematopoietic cell lines (E. Huberman and M. F. Callaham, Proc. Natl. Acad. Sci. USA, 76: 1293-1297, 1979; J. Lotem and L. Sachs, Proc. Natl. Acad. Sci. USA, 76: 5158-5162, 1979; G. R...
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| Veröffentlicht in: | Clinical cancer research 2002-08, Vol.8 (8), p.2512-2518 |
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| creator | STRAIR, Roger K SCHAAR, Dale RABSON, Arnold B CHANG, Richard CONNEY, Allan GOODELL, Lauri AISNER, Joseph CHIN, Khew-Voon EID, Joseph SENZON, Rachelle XIAO XING CUI ZHENG TAO HAN KNOX, Beth |
| description | Phorbol esters are capable of inducing a broad range of cellular effects,including the maturation/differentiation of hematopoietic cell lines (E. Huberman and M. F. Callaham, Proc. Natl. Acad. Sci. USA, 76: 1293-1297, 1979; J. Lotem and L. Sachs, Proc. Natl. Acad. Sci. USA, 76: 5158-5162, 1979; G. Rovera et al., Proc. Natl. Acad. Sci. USA, 76: 2779-2783, 1979; H. P. Koeffler, J. Clin. Investig., 66: 1101-1108, 1980). The ability to induce this differentiation at very low concentrations stimulated investigators to administer a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), to patients with myeloid leukemias in the People's Republic of China (Z. T. Han et al., Proc. Natl. Acad. Sci. USA, 95: 5357-5361, 1998). The tolerability of this therapy in China prompted Phase I studies of TPA in the United States. The purpose of this report is to demonstrate the tolerance of TPA at doses that result in detectable biological activity in blood and malignant cells.
TPA was administered to patients with relapsed/refractory hematological malignancies.
Phenotypic effects were detected in malignant cells and TPA-associated biological activity was present in blood for up to several hours after the infusion.
These studies confirm the feasibility of TPA administration to humans and establish the foundation for the development of phorbol esters as therapy for patients with a variety of malignant and nonmalignant disorders. |
| format | Article |
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TPA was administered to patients with relapsed/refractory hematological malignancies.
Phenotypic effects were detected in malignant cells and TPA-associated biological activity was present in blood for up to several hours after the infusion.
These studies confirm the feasibility of TPA administration to humans and establish the foundation for the development of phorbol esters as therapy for patients with a variety of malignant and nonmalignant disorders.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 12171877</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Antineoplastic agents ; Biological and medical sciences ; Cells, Cultured ; Chemotherapy ; DNA, Complementary - metabolism ; Female ; Hematologic Neoplasms - drug therapy ; Hematologic Neoplasms - metabolism ; HL-60 Cells ; Humans ; Immunophenotyping ; Male ; Medical sciences ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Pharmacology. Drug treatments ; Phenotype ; Tetradecanoylphorbol Acetate - pharmacology ; Tetradecanoylphorbol Acetate - therapeutic use ; Time Factors</subject><ispartof>Clinical cancer research, 2002-08, Vol.8 (8), p.2512-2518</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13848165$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12171877$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>STRAIR, Roger K</creatorcontrib><creatorcontrib>SCHAAR, Dale</creatorcontrib><creatorcontrib>RABSON, Arnold B</creatorcontrib><creatorcontrib>CHANG, Richard</creatorcontrib><creatorcontrib>CONNEY, Allan</creatorcontrib><creatorcontrib>GOODELL, Lauri</creatorcontrib><creatorcontrib>AISNER, Joseph</creatorcontrib><creatorcontrib>CHIN, Khew-Voon</creatorcontrib><creatorcontrib>EID, Joseph</creatorcontrib><creatorcontrib>SENZON, Rachelle</creatorcontrib><creatorcontrib>XIAO XING CUI</creatorcontrib><creatorcontrib>ZHENG TAO HAN</creatorcontrib><creatorcontrib>KNOX, Beth</creatorcontrib><title>Administration of a Phorbol ester to patients with hematological malignancies: Preliminary results from a Phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Phorbol esters are capable of inducing a broad range of cellular effects,including the maturation/differentiation of hematopoietic cell lines (E. Huberman and M. F. Callaham, Proc. Natl. Acad. Sci. USA, 76: 1293-1297, 1979; J. Lotem and L. Sachs, Proc. Natl. Acad. Sci. USA, 76: 5158-5162, 1979; G. Rovera et al., Proc. Natl. Acad. Sci. USA, 76: 2779-2783, 1979; H. P. Koeffler, J. Clin. Investig., 66: 1101-1108, 1980). The ability to induce this differentiation at very low concentrations stimulated investigators to administer a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), to patients with myeloid leukemias in the People's Republic of China (Z. T. Han et al., Proc. Natl. Acad. Sci. USA, 95: 5357-5361, 1998). The tolerability of this therapy in China prompted Phase I studies of TPA in the United States. The purpose of this report is to demonstrate the tolerance of TPA at doses that result in detectable biological activity in blood and malignant cells.
TPA was administered to patients with relapsed/refractory hematological malignancies.
Phenotypic effects were detected in malignant cells and TPA-associated biological activity was present in blood for up to several hours after the infusion.
These studies confirm the feasibility of TPA administration to humans and establish the foundation for the development of phorbol esters as therapy for patients with a variety of malignant and nonmalignant disorders.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>Chemotherapy</subject><subject>DNA, Complementary - metabolism</subject><subject>Female</subject><subject>Hematologic Neoplasms - drug therapy</subject><subject>Hematologic Neoplasms - metabolism</subject><subject>HL-60 Cells</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenotype</subject><subject>Tetradecanoylphorbol Acetate - pharmacology</subject><subject>Tetradecanoylphorbol Acetate - therapeutic use</subject><subject>Time Factors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFUEtLAzEQXkSxvv6C5OIxkGQ3m6y3UnwUCu1BzzKbnbWR7GZJUqT_yJ9ptBUvMwPzzfeYk-KCS6loKWp5mmemNGVVKWbFZYwfjPGKs-q8mHHBFddKXRRf826wo40pQLJ-JL4nQDZbH1rvCMaEgSRPprzEMUXyadOWbHGA5J1_twYcGcDZ9xFGYzHek01AZzMjhD0JGHcuH_XBD7-sEJEsiXFZ8OcyBZtrVuSCrmnC7KFDA6Pfu-nggPKSgsEECa-Lsx5cxJtjvypeHx9eFs90tX5aLuYrOolSJWqgqbRiLTfSSIYoQLWoKialwMborlW85k1eKwm16VktZY-i16KpGq1bXV4VtwfeadcO2L1NwQ45zNvfyzLg7giAmFP04Sd6_MeVutK8luU38YB4-g</recordid><startdate>20020801</startdate><enddate>20020801</enddate><creator>STRAIR, Roger K</creator><creator>SCHAAR, Dale</creator><creator>RABSON, Arnold B</creator><creator>CHANG, Richard</creator><creator>CONNEY, Allan</creator><creator>GOODELL, Lauri</creator><creator>AISNER, Joseph</creator><creator>CHIN, Khew-Voon</creator><creator>EID, Joseph</creator><creator>SENZON, Rachelle</creator><creator>XIAO XING CUI</creator><creator>ZHENG TAO HAN</creator><creator>KNOX, Beth</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></search><sort><creationdate>20020801</creationdate><title>Administration of a Phorbol ester to patients with hematological malignancies: Preliminary results from a Phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate</title><author>STRAIR, Roger K ; SCHAAR, Dale ; RABSON, Arnold B ; CHANG, Richard ; CONNEY, Allan ; GOODELL, Lauri ; AISNER, Joseph ; CHIN, Khew-Voon ; EID, Joseph ; SENZON, Rachelle ; XIAO XING CUI ; ZHENG TAO HAN ; KNOX, Beth</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p237t-ca94870b1c5c50ee2a7be740552e9c8db71619b1c75a6cf0655fe2f8294988b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Cells, Cultured</topic><topic>Chemotherapy</topic><topic>DNA, Complementary - metabolism</topic><topic>Female</topic><topic>Hematologic Neoplasms - drug therapy</topic><topic>Hematologic Neoplasms - metabolism</topic><topic>HL-60 Cells</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenotype</topic><topic>Tetradecanoylphorbol Acetate - pharmacology</topic><topic>Tetradecanoylphorbol Acetate - therapeutic use</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>STRAIR, Roger K</creatorcontrib><creatorcontrib>SCHAAR, Dale</creatorcontrib><creatorcontrib>RABSON, Arnold B</creatorcontrib><creatorcontrib>CHANG, Richard</creatorcontrib><creatorcontrib>CONNEY, Allan</creatorcontrib><creatorcontrib>GOODELL, Lauri</creatorcontrib><creatorcontrib>AISNER, Joseph</creatorcontrib><creatorcontrib>CHIN, Khew-Voon</creatorcontrib><creatorcontrib>EID, Joseph</creatorcontrib><creatorcontrib>SENZON, Rachelle</creatorcontrib><creatorcontrib>XIAO XING CUI</creatorcontrib><creatorcontrib>ZHENG TAO HAN</creatorcontrib><creatorcontrib>KNOX, Beth</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>STRAIR, Roger K</au><au>SCHAAR, Dale</au><au>RABSON, Arnold B</au><au>CHANG, Richard</au><au>CONNEY, Allan</au><au>GOODELL, Lauri</au><au>AISNER, Joseph</au><au>CHIN, Khew-Voon</au><au>EID, Joseph</au><au>SENZON, Rachelle</au><au>XIAO XING CUI</au><au>ZHENG TAO HAN</au><au>KNOX, Beth</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Administration of a Phorbol ester to patients with hematological malignancies: Preliminary results from a Phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2002-08-01</date><risdate>2002</risdate><volume>8</volume><issue>8</issue><spage>2512</spage><epage>2518</epage><pages>2512-2518</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Phorbol esters are capable of inducing a broad range of cellular effects,including the maturation/differentiation of hematopoietic cell lines (E. Huberman and M. F. Callaham, Proc. Natl. Acad. Sci. USA, 76: 1293-1297, 1979; J. Lotem and L. Sachs, Proc. Natl. Acad. Sci. USA, 76: 5158-5162, 1979; G. Rovera et al., Proc. Natl. Acad. Sci. USA, 76: 2779-2783, 1979; H. P. Koeffler, J. Clin. Investig., 66: 1101-1108, 1980). The ability to induce this differentiation at very low concentrations stimulated investigators to administer a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), to patients with myeloid leukemias in the People's Republic of China (Z. T. Han et al., Proc. Natl. Acad. Sci. USA, 95: 5357-5361, 1998). The tolerability of this therapy in China prompted Phase I studies of TPA in the United States. The purpose of this report is to demonstrate the tolerance of TPA at doses that result in detectable biological activity in blood and malignant cells.
TPA was administered to patients with relapsed/refractory hematological malignancies.
Phenotypic effects were detected in malignant cells and TPA-associated biological activity was present in blood for up to several hours after the infusion.
These studies confirm the feasibility of TPA administration to humans and establish the foundation for the development of phorbol esters as therapy for patients with a variety of malignant and nonmalignant disorders.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>12171877</pmid><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2002-08, Vol.8 (8), p.2512-2518 |
| issn | 1078-0432 1557-3265 |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Aged Antineoplastic agents Biological and medical sciences Cells, Cultured Chemotherapy DNA, Complementary - metabolism Female Hematologic Neoplasms - drug therapy Hematologic Neoplasms - metabolism HL-60 Cells Humans Immunophenotyping Male Medical sciences Middle Aged Oligonucleotide Array Sequence Analysis Pharmacology. Drug treatments Phenotype Tetradecanoylphorbol Acetate - pharmacology Tetradecanoylphorbol Acetate - therapeutic use Time Factors |
| title | Administration of a Phorbol ester to patients with hematological malignancies: Preliminary results from a Phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate |
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