The in Vivo Effect of Bryostatin-1 on Paclitaxel-induced Tumor Growth, Mitotic Entry, and Blood Flow
Pretreatment of tumor cells with the protein kinase C (PKC) inhibitor bryostatin-1 enhances the cytotoxicity of most chemotherapeutic agents. However, in the case of paclitaxel, this effect has been shown in vitro to be best achieved when bryostatin-1 follows (rather than precedes) paclitaxel treatm...
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| creator | Koutcher, J A Motwani, M Zakian, K L Li, X K Matei, C Dyke, J P Ballon, D Yoo, H H Schwartz, G K |
| description | Pretreatment
of tumor cells with the protein kinase C (PKC) inhibitor bryostatin-1
enhances the cytotoxicity of most chemotherapeutic agents. However, in
the case of paclitaxel, this effect has been shown in
vitro to be best achieved when bryostatin-1 follows (rather
than precedes) paclitaxel treatment. With combination trials of
bryostatin-1 and paclitaxel planned for clinical trials and with only
in vitro data available regarding drug sequence, we
elected to undertake an in vivo study evaluating the
effect of sequential bryostatin-1 and paclitaxel in a tumor-bearing
mouse model and to correlate this effect to cell cycle events, tumor
metabolism, and tumor blood flow. At the maximum tolerated i.p. dose,
bryostatin-1 at 80 μg/kg resulted in a small but significant increase
in tumor doubling time (4.2 ± 0.3 days) compared with control
tumors (3.0 ± 0.3 days; P < 0.01). Mice
treated with i.v. paclitaxel, administered at a dose of 12 mg/kg every
12 h for three doses, weekly for 3 weeks, had a tumor doubling
time of 23.4 ± 1.7 days. Mice pretreated with i.p. bryostatin-1
(80 μg/kg) followed 12 h later by i.v. paclitaxel (12 mg/kg
every 12h for three doses) weekly for 3 weeks had a tumor doubling time
of 9.7 ± 1.1 days. This was significantly less
( P < .001) than paclitaxel alone, which indicated
an inhibitory effect by bryostatin-1 on paclitaxel therapy. In
comparison, tumor-bearing mice that were treated with the same dose but
with the sequence of paclitaxel followed by bryostatin-1 had a tumor
doubling time of 29.6 ± 0.6 days. This was significantly greater
than the tumor doubling times for any condition tested
( P < 0.01), demonstrating the sequence dependence
of this combination. The efficacy of paclitaxel is dependent on mitotic
entry, a step that requires activation of p34 cdc2 kinase
activity. Treatment with paclitaxel in vivo increased
p34 cdc2 kinase activity in the mouse mammary tumors,
whereas administration of bryostatin-1 before paclitaxel prevented the
p34 cdc2 kinase activation by paclitaxel. This was further
evaluated in vitro by flow cytometry in MKN-74 human
gastric cancer cells. As determined by MPM-2 labeling, which identifies
cells in mitosis, pretreatment with bryostatin-1 prevented
paclitaxel-treated cells from entering mitosis. Bryostatin-1 has been
reported to induce changes in muscle metabolism and to decrease muscle
blood flow. These events could impact on the interaction of
bryostatin-1 with paclitaxel. Using proton-decoupled phosp |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_71054796</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71054796</sourcerecordid><originalsourceid>FETCH-LOGICAL-h239t-b271c703ae2bcf73ad88651a00e31b67a095645081ff969c3b70a825a0d3a4d63</originalsourceid><addsrcrecordid>eNo10EFPwyAYBuDGaNyc_gXDSS9rAgUKPbplmyYzepheCQVqMS1MoM79e2c2T9-bvE_ew3eWjRGlLMdFSc8PGTKeQ4KLUXYV4yeEiCBILrPRoWC84sU405vWAOvAu_32YNE0RiXgGzALex-TTNblCHgHXqXqbJI_psut04MyGmyG3gewCn6X2il4tsknq8DCpbCfAuk0mHXea7Ds_O46u2hkF83N6U6yt-ViM3_M1y-rp_nDOm8LXKW8LhhSDGJpilo1DEvNeUmRhNBgVJdMwoqWhEKOmqYqK4VrBiUvqIQaS6JLPMnujrvb4L8GE5PobVSm66QzfoiCIUgJq_7g7QkOdW-02Abby7AX_385gPsjaO1Hu7PBCCWdMiGYaGRQrSgFEYhUHP8CVkVsVg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71054796</pqid></control><display><type>article</type><title>The in Vivo Effect of Bryostatin-1 on Paclitaxel-induced Tumor Growth, Mitotic Entry, and Blood Flow</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Koutcher, J A ; Motwani, M ; Zakian, K L ; Li, X K ; Matei, C ; Dyke, J P ; Ballon, D ; Yoo, H H ; Schwartz, G K</creator><creatorcontrib>Koutcher, J A ; Motwani, M ; Zakian, K L ; Li, X K ; Matei, C ; Dyke, J P ; Ballon, D ; Yoo, H H ; Schwartz, G K</creatorcontrib><description>Pretreatment
of tumor cells with the protein kinase C (PKC) inhibitor bryostatin-1
enhances the cytotoxicity of most chemotherapeutic agents. However, in
the case of paclitaxel, this effect has been shown in
vitro to be best achieved when bryostatin-1 follows (rather
than precedes) paclitaxel treatment. With combination trials of
bryostatin-1 and paclitaxel planned for clinical trials and with only
in vitro data available regarding drug sequence, we
elected to undertake an in vivo study evaluating the
effect of sequential bryostatin-1 and paclitaxel in a tumor-bearing
mouse model and to correlate this effect to cell cycle events, tumor
metabolism, and tumor blood flow. At the maximum tolerated i.p. dose,
bryostatin-1 at 80 μg/kg resulted in a small but significant increase
in tumor doubling time (4.2 ± 0.3 days) compared with control
tumors (3.0 ± 0.3 days; P < 0.01). Mice
treated with i.v. paclitaxel, administered at a dose of 12 mg/kg every
12 h for three doses, weekly for 3 weeks, had a tumor doubling
time of 23.4 ± 1.7 days. Mice pretreated with i.p. bryostatin-1
(80 μg/kg) followed 12 h later by i.v. paclitaxel (12 mg/kg
every 12h for three doses) weekly for 3 weeks had a tumor doubling time
of 9.7 ± 1.1 days. This was significantly less
( P < .001) than paclitaxel alone, which indicated
an inhibitory effect by bryostatin-1 on paclitaxel therapy. In
comparison, tumor-bearing mice that were treated with the same dose but
with the sequence of paclitaxel followed by bryostatin-1 had a tumor
doubling time of 29.6 ± 0.6 days. This was significantly greater
than the tumor doubling times for any condition tested
( P < 0.01), demonstrating the sequence dependence
of this combination. The efficacy of paclitaxel is dependent on mitotic
entry, a step that requires activation of p34 cdc2 kinase
activity. Treatment with paclitaxel in vivo increased
p34 cdc2 kinase activity in the mouse mammary tumors,
whereas administration of bryostatin-1 before paclitaxel prevented the
p34 cdc2 kinase activation by paclitaxel. This was further
evaluated in vitro by flow cytometry in MKN-74 human
gastric cancer cells. As determined by MPM-2 labeling, which identifies
cells in mitosis, pretreatment with bryostatin-1 prevented
paclitaxel-treated cells from entering mitosis. Bryostatin-1 has been
reported to induce changes in muscle metabolism and to decrease muscle
blood flow. These events could impact on the interaction of
bryostatin-1 with paclitaxel. Using proton-decoupled phosphorus
nuclear magnetic resonance ( 31 P-NMR) spectroscopy
in vivo , bryostatin-1 at 80 μg/kg induced a decrease
in both intratumoral pH and high-energy phosphates. In
vivo perfusion studies, using dynamic enhanced NMR imaging with
gadolinium diethylenetriamine pentaacetic acid, also
demonstrated decreased tumor blood flow. These studies suggest that the
inhibition of tumor response to paclitaxel by bryostatin-1 is
multifactorial and includes such diverse factors as inhibition of cell
entry into mitosis, a decrease in pH and energy metabolism, and a
decrease in tumor blood flow. These results indicate that, as this
combination enters Phase I clinical trials, the sequence of paclitaxel
followed by bryostatin-1 will be critical in the clinical trial design.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 10778982</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bryostatins ; CDC2 Protein Kinase - drug effects ; CDC2 Protein Kinase - metabolism ; Cell Division - drug effects ; Energy Metabolism - drug effects ; Humans ; Hydrogen-Ion Concentration ; Lactones - administration & dosage ; Macrolides ; Magnetic Resonance Spectroscopy ; Male ; Mice ; Mice, Inbred C3H ; Mitosis - drug effects ; Neoplasms, Experimental - blood supply ; Neoplasms, Experimental - drug therapy ; Neoplasms, Experimental - pathology ; Paclitaxel - administration & dosage ; Phosphocreatine - drug effects ; Phosphocreatine - metabolism ; Regional Blood Flow - drug effects ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - pathology ; Tumor Cells, Cultured</subject><ispartof>Clinical cancer research, 2000-04, Vol.6 (4), p.1498-1507</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10778982$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koutcher, J A</creatorcontrib><creatorcontrib>Motwani, M</creatorcontrib><creatorcontrib>Zakian, K L</creatorcontrib><creatorcontrib>Li, X K</creatorcontrib><creatorcontrib>Matei, C</creatorcontrib><creatorcontrib>Dyke, J P</creatorcontrib><creatorcontrib>Ballon, D</creatorcontrib><creatorcontrib>Yoo, H H</creatorcontrib><creatorcontrib>Schwartz, G K</creatorcontrib><title>The in Vivo Effect of Bryostatin-1 on Paclitaxel-induced Tumor Growth, Mitotic Entry, and Blood Flow</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Pretreatment
of tumor cells with the protein kinase C (PKC) inhibitor bryostatin-1
enhances the cytotoxicity of most chemotherapeutic agents. However, in
the case of paclitaxel, this effect has been shown in
vitro to be best achieved when bryostatin-1 follows (rather
than precedes) paclitaxel treatment. With combination trials of
bryostatin-1 and paclitaxel planned for clinical trials and with only
in vitro data available regarding drug sequence, we
elected to undertake an in vivo study evaluating the
effect of sequential bryostatin-1 and paclitaxel in a tumor-bearing
mouse model and to correlate this effect to cell cycle events, tumor
metabolism, and tumor blood flow. At the maximum tolerated i.p. dose,
bryostatin-1 at 80 μg/kg resulted in a small but significant increase
in tumor doubling time (4.2 ± 0.3 days) compared with control
tumors (3.0 ± 0.3 days; P < 0.01). Mice
treated with i.v. paclitaxel, administered at a dose of 12 mg/kg every
12 h for three doses, weekly for 3 weeks, had a tumor doubling
time of 23.4 ± 1.7 days. Mice pretreated with i.p. bryostatin-1
(80 μg/kg) followed 12 h later by i.v. paclitaxel (12 mg/kg
every 12h for three doses) weekly for 3 weeks had a tumor doubling time
of 9.7 ± 1.1 days. This was significantly less
( P < .001) than paclitaxel alone, which indicated
an inhibitory effect by bryostatin-1 on paclitaxel therapy. In
comparison, tumor-bearing mice that were treated with the same dose but
with the sequence of paclitaxel followed by bryostatin-1 had a tumor
doubling time of 29.6 ± 0.6 days. This was significantly greater
than the tumor doubling times for any condition tested
( P < 0.01), demonstrating the sequence dependence
of this combination. The efficacy of paclitaxel is dependent on mitotic
entry, a step that requires activation of p34 cdc2 kinase
activity. Treatment with paclitaxel in vivo increased
p34 cdc2 kinase activity in the mouse mammary tumors,
whereas administration of bryostatin-1 before paclitaxel prevented the
p34 cdc2 kinase activation by paclitaxel. This was further
evaluated in vitro by flow cytometry in MKN-74 human
gastric cancer cells. As determined by MPM-2 labeling, which identifies
cells in mitosis, pretreatment with bryostatin-1 prevented
paclitaxel-treated cells from entering mitosis. Bryostatin-1 has been
reported to induce changes in muscle metabolism and to decrease muscle
blood flow. These events could impact on the interaction of
bryostatin-1 with paclitaxel. Using proton-decoupled phosphorus
nuclear magnetic resonance ( 31 P-NMR) spectroscopy
in vivo , bryostatin-1 at 80 μg/kg induced a decrease
in both intratumoral pH and high-energy phosphates. In
vivo perfusion studies, using dynamic enhanced NMR imaging with
gadolinium diethylenetriamine pentaacetic acid, also
demonstrated decreased tumor blood flow. These studies suggest that the
inhibition of tumor response to paclitaxel by bryostatin-1 is
multifactorial and includes such diverse factors as inhibition of cell
entry into mitosis, a decrease in pH and energy metabolism, and a
decrease in tumor blood flow. These results indicate that, as this
combination enters Phase I clinical trials, the sequence of paclitaxel
followed by bryostatin-1 will be critical in the clinical trial design.</description><subject>Animals</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bryostatins</subject><subject>CDC2 Protein Kinase - drug effects</subject><subject>CDC2 Protein Kinase - metabolism</subject><subject>Cell Division - drug effects</subject><subject>Energy Metabolism - drug effects</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Lactones - administration & dosage</subject><subject>Macrolides</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C3H</subject><subject>Mitosis - drug effects</subject><subject>Neoplasms, Experimental - blood supply</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Neoplasms, Experimental - pathology</subject><subject>Paclitaxel - administration & dosage</subject><subject>Phosphocreatine - drug effects</subject><subject>Phosphocreatine - metabolism</subject><subject>Regional Blood Flow - drug effects</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach Neoplasms - pathology</subject><subject>Tumor Cells, Cultured</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo10EFPwyAYBuDGaNyc_gXDSS9rAgUKPbplmyYzepheCQVqMS1MoM79e2c2T9-bvE_ew3eWjRGlLMdFSc8PGTKeQ4KLUXYV4yeEiCBILrPRoWC84sU405vWAOvAu_32YNE0RiXgGzALex-TTNblCHgHXqXqbJI_psut04MyGmyG3gewCn6X2il4tsknq8DCpbCfAuk0mHXea7Ds_O46u2hkF83N6U6yt-ViM3_M1y-rp_nDOm8LXKW8LhhSDGJpilo1DEvNeUmRhNBgVJdMwoqWhEKOmqYqK4VrBiUvqIQaS6JLPMnujrvb4L8GE5PobVSm66QzfoiCIUgJq_7g7QkOdW-02Abby7AX_385gPsjaO1Hu7PBCCWdMiGYaGRQrSgFEYhUHP8CVkVsVg</recordid><startdate>20000401</startdate><enddate>20000401</enddate><creator>Koutcher, J A</creator><creator>Motwani, M</creator><creator>Zakian, K L</creator><creator>Li, X K</creator><creator>Matei, C</creator><creator>Dyke, J P</creator><creator>Ballon, D</creator><creator>Yoo, H H</creator><creator>Schwartz, G K</creator><general>American Association for Cancer Research</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20000401</creationdate><title>The in Vivo Effect of Bryostatin-1 on Paclitaxel-induced Tumor Growth, Mitotic Entry, and Blood Flow</title><author>Koutcher, J A ; Motwani, M ; Zakian, K L ; Li, X K ; Matei, C ; Dyke, J P ; Ballon, D ; Yoo, H H ; Schwartz, G K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h239t-b271c703ae2bcf73ad88651a00e31b67a095645081ff969c3b70a825a0d3a4d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Bryostatins</topic><topic>CDC2 Protein Kinase - drug effects</topic><topic>CDC2 Protein Kinase - metabolism</topic><topic>Cell Division - drug effects</topic><topic>Energy Metabolism - drug effects</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>Lactones - administration & dosage</topic><topic>Macrolides</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C3H</topic><topic>Mitosis - drug effects</topic><topic>Neoplasms, Experimental - blood supply</topic><topic>Neoplasms, Experimental - drug therapy</topic><topic>Neoplasms, Experimental - pathology</topic><topic>Paclitaxel - administration & dosage</topic><topic>Phosphocreatine - drug effects</topic><topic>Phosphocreatine - metabolism</topic><topic>Regional Blood Flow - drug effects</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Stomach Neoplasms - pathology</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koutcher, J A</creatorcontrib><creatorcontrib>Motwani, M</creatorcontrib><creatorcontrib>Zakian, K L</creatorcontrib><creatorcontrib>Li, X K</creatorcontrib><creatorcontrib>Matei, C</creatorcontrib><creatorcontrib>Dyke, J P</creatorcontrib><creatorcontrib>Ballon, D</creatorcontrib><creatorcontrib>Yoo, H H</creatorcontrib><creatorcontrib>Schwartz, G K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koutcher, J A</au><au>Motwani, M</au><au>Zakian, K L</au><au>Li, X K</au><au>Matei, C</au><au>Dyke, J P</au><au>Ballon, D</au><au>Yoo, H H</au><au>Schwartz, G K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The in Vivo Effect of Bryostatin-1 on Paclitaxel-induced Tumor Growth, Mitotic Entry, and Blood Flow</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2000-04-01</date><risdate>2000</risdate><volume>6</volume><issue>4</issue><spage>1498</spage><epage>1507</epage><pages>1498-1507</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Pretreatment
of tumor cells with the protein kinase C (PKC) inhibitor bryostatin-1
enhances the cytotoxicity of most chemotherapeutic agents. However, in
the case of paclitaxel, this effect has been shown in
vitro to be best achieved when bryostatin-1 follows (rather
than precedes) paclitaxel treatment. With combination trials of
bryostatin-1 and paclitaxel planned for clinical trials and with only
in vitro data available regarding drug sequence, we
elected to undertake an in vivo study evaluating the
effect of sequential bryostatin-1 and paclitaxel in a tumor-bearing
mouse model and to correlate this effect to cell cycle events, tumor
metabolism, and tumor blood flow. At the maximum tolerated i.p. dose,
bryostatin-1 at 80 μg/kg resulted in a small but significant increase
in tumor doubling time (4.2 ± 0.3 days) compared with control
tumors (3.0 ± 0.3 days; P < 0.01). Mice
treated with i.v. paclitaxel, administered at a dose of 12 mg/kg every
12 h for three doses, weekly for 3 weeks, had a tumor doubling
time of 23.4 ± 1.7 days. Mice pretreated with i.p. bryostatin-1
(80 μg/kg) followed 12 h later by i.v. paclitaxel (12 mg/kg
every 12h for three doses) weekly for 3 weeks had a tumor doubling time
of 9.7 ± 1.1 days. This was significantly less
( P < .001) than paclitaxel alone, which indicated
an inhibitory effect by bryostatin-1 on paclitaxel therapy. In
comparison, tumor-bearing mice that were treated with the same dose but
with the sequence of paclitaxel followed by bryostatin-1 had a tumor
doubling time of 29.6 ± 0.6 days. This was significantly greater
than the tumor doubling times for any condition tested
( P < 0.01), demonstrating the sequence dependence
of this combination. The efficacy of paclitaxel is dependent on mitotic
entry, a step that requires activation of p34 cdc2 kinase
activity. Treatment with paclitaxel in vivo increased
p34 cdc2 kinase activity in the mouse mammary tumors,
whereas administration of bryostatin-1 before paclitaxel prevented the
p34 cdc2 kinase activation by paclitaxel. This was further
evaluated in vitro by flow cytometry in MKN-74 human
gastric cancer cells. As determined by MPM-2 labeling, which identifies
cells in mitosis, pretreatment with bryostatin-1 prevented
paclitaxel-treated cells from entering mitosis. Bryostatin-1 has been
reported to induce changes in muscle metabolism and to decrease muscle
blood flow. These events could impact on the interaction of
bryostatin-1 with paclitaxel. Using proton-decoupled phosphorus
nuclear magnetic resonance ( 31 P-NMR) spectroscopy
in vivo , bryostatin-1 at 80 μg/kg induced a decrease
in both intratumoral pH and high-energy phosphates. In
vivo perfusion studies, using dynamic enhanced NMR imaging with
gadolinium diethylenetriamine pentaacetic acid, also
demonstrated decreased tumor blood flow. These studies suggest that the
inhibition of tumor response to paclitaxel by bryostatin-1 is
multifactorial and includes such diverse factors as inhibition of cell
entry into mitosis, a decrease in pH and energy metabolism, and a
decrease in tumor blood flow. These results indicate that, as this
combination enters Phase I clinical trials, the sequence of paclitaxel
followed by bryostatin-1 will be critical in the clinical trial design.</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>10778982</pmid><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2000-04, Vol.6 (4), p.1498-1507 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71054796 |
| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bryostatins CDC2 Protein Kinase - drug effects CDC2 Protein Kinase - metabolism Cell Division - drug effects Energy Metabolism - drug effects Humans Hydrogen-Ion Concentration Lactones - administration & dosage Macrolides Magnetic Resonance Spectroscopy Male Mice Mice, Inbred C3H Mitosis - drug effects Neoplasms, Experimental - blood supply Neoplasms, Experimental - drug therapy Neoplasms, Experimental - pathology Paclitaxel - administration & dosage Phosphocreatine - drug effects Phosphocreatine - metabolism Regional Blood Flow - drug effects Stomach Neoplasms - drug therapy Stomach Neoplasms - pathology Tumor Cells, Cultured |
| title | The in Vivo Effect of Bryostatin-1 on Paclitaxel-induced Tumor Growth, Mitotic Entry, and Blood Flow |
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