Anti-Tumor Effects of a Penetratin Peptide Targeting Transcription of E2F-1, 2 and 3a Is Enhanced When Used in Combination with Pemetrexed or Cisplatin
We tested the antitumor effects of a modified E2F peptide substituting D-Arg for L-Arg, conjugated to penetratin (PEP) against solid tumor cell lines and the CCRF-leukemia cell line, alone and in combination with pemetrexed or with cisplatin. For - studies, the peptide was encapsulated in PEGylated...
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| Veröffentlicht in: | Cancers 2021-02, Vol.13 (5), p.972 |
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| creator | Rather, Gulam Mohmad Anyanwu, Michael Minko, Tamara Garbuzenko, Olga Szekely, Zoltan Bertino, Joseph R |
| description | We tested the antitumor effects of a modified E2F peptide substituting D-Arg for L-Arg, conjugated to penetratin (PEP) against solid tumor cell lines and the CCRF-leukemia cell line, alone and in combination with pemetrexed or with cisplatin. For
-
studies, the peptide was encapsulated in PEGylated liposomes (PL-PEP) to increase half-life and stability.
Prostate cancer (DU145 and PC3), breast cancer (MCF7, MDA-MB-468, and 4T1), lymphoma (CCRF-CEM), and non-small cell lung cancer (NSCLC) cell lines (H2009, H441, H1975, and H2228) were treated with D-Arg PEP in combination with cisplatin or pemetrexed. Western blot analysis was performed on the NSCLC for E2F-1, pRb, thymidylate synthase, and thymidine kinase. The H2009 cell line was selected for an
-
study.
When the PEP was combined with cisplatin and tested against solid tumor cell lines and the CCRF-CEM leukemia cell line, there was a modest synergistic effect. A marked synergistic effect was seen when the combination of pemetrexed and the PEP was tested against the adenocarcinoma lung cancer cell lines. The addition of the PEP to pemetrexed enhanced the antitumor effects of pemetrexed in a xenograft of the H2009 in mice.
The D-Arg PEP in combination with cisplatin caused synergistic cell kill against prostate, breast, lung cancers, and the CCRF-CEM cell line. Marked synergy resulted when the D-Arg PEP was used in combination with pemetrexed against the lung adenocarcinoma cell lines. A xenograft study using the PL-PEP in combination with pemetrexed showed enhanced anti-tumor effects compared to each drug alone. |
| doi_str_mv | 10.3390/cancers13050972 |
| format | Article |
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-
studies, the peptide was encapsulated in PEGylated liposomes (PL-PEP) to increase half-life and stability.
Prostate cancer (DU145 and PC3), breast cancer (MCF7, MDA-MB-468, and 4T1), lymphoma (CCRF-CEM), and non-small cell lung cancer (NSCLC) cell lines (H2009, H441, H1975, and H2228) were treated with D-Arg PEP in combination with cisplatin or pemetrexed. Western blot analysis was performed on the NSCLC for E2F-1, pRb, thymidylate synthase, and thymidine kinase. The H2009 cell line was selected for an
-
study.
When the PEP was combined with cisplatin and tested against solid tumor cell lines and the CCRF-CEM leukemia cell line, there was a modest synergistic effect. A marked synergistic effect was seen when the combination of pemetrexed and the PEP was tested against the adenocarcinoma lung cancer cell lines. The addition of the PEP to pemetrexed enhanced the antitumor effects of pemetrexed in a xenograft of the H2009 in mice.
The D-Arg PEP in combination with cisplatin caused synergistic cell kill against prostate, breast, lung cancers, and the CCRF-CEM cell line. Marked synergy resulted when the D-Arg PEP was used in combination with pemetrexed against the lung adenocarcinoma cell lines. A xenograft study using the PL-PEP in combination with pemetrexed showed enhanced anti-tumor effects compared to each drug alone.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13050972</identifier><identifier>PMID: 33652640</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adenocarcinoma ; Antitumor activity ; Apoptosis ; Breast cancer ; Cell cycle ; Cell growth ; Cisplatin ; Deoxyribonucleic acid ; Dihydrofolate reductase ; DNA ; DNA damage ; DNA repair ; E2F protein ; E2F1 protein ; Enzymes ; Gene amplification ; Kinases ; Lung cancer ; Lymphoma ; Mutation ; Non-small cell lung carcinoma ; Peptides ; Phosphorylation ; Prostate ; Prostate cancer ; Proteins ; Small cell lung carcinoma ; Solid tumors ; Thymidine ; Thymidine kinase ; Thymidylate synthase ; Transcription ; Tumor cell lines ; Tumors ; Xenografts</subject><ispartof>Cancers, 2021-02, Vol.13 (5), p.972</ispartof><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-826bb391b9214a20da4a89b68ec24f12994f7db45129ddab8bd258772ee886253</citedby><cites>FETCH-LOGICAL-c421t-826bb391b9214a20da4a89b68ec24f12994f7db45129ddab8bd258772ee886253</cites><orcidid>0000-0003-2175-2263</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956530/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956530/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33652640$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rather, Gulam Mohmad</creatorcontrib><creatorcontrib>Anyanwu, Michael</creatorcontrib><creatorcontrib>Minko, Tamara</creatorcontrib><creatorcontrib>Garbuzenko, Olga</creatorcontrib><creatorcontrib>Szekely, Zoltan</creatorcontrib><creatorcontrib>Bertino, Joseph R</creatorcontrib><title>Anti-Tumor Effects of a Penetratin Peptide Targeting Transcription of E2F-1, 2 and 3a Is Enhanced When Used in Combination with Pemetrexed or Cisplatin</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>We tested the antitumor effects of a modified E2F peptide substituting D-Arg for L-Arg, conjugated to penetratin (PEP) against solid tumor cell lines and the CCRF-leukemia cell line, alone and in combination with pemetrexed or with cisplatin. For
-
studies, the peptide was encapsulated in PEGylated liposomes (PL-PEP) to increase half-life and stability.
Prostate cancer (DU145 and PC3), breast cancer (MCF7, MDA-MB-468, and 4T1), lymphoma (CCRF-CEM), and non-small cell lung cancer (NSCLC) cell lines (H2009, H441, H1975, and H2228) were treated with D-Arg PEP in combination with cisplatin or pemetrexed. Western blot analysis was performed on the NSCLC for E2F-1, pRb, thymidylate synthase, and thymidine kinase. The H2009 cell line was selected for an
-
study.
When the PEP was combined with cisplatin and tested against solid tumor cell lines and the CCRF-CEM leukemia cell line, there was a modest synergistic effect. A marked synergistic effect was seen when the combination of pemetrexed and the PEP was tested against the adenocarcinoma lung cancer cell lines. The addition of the PEP to pemetrexed enhanced the antitumor effects of pemetrexed in a xenograft of the H2009 in mice.
The D-Arg PEP in combination with cisplatin caused synergistic cell kill against prostate, breast, lung cancers, and the CCRF-CEM cell line. Marked synergy resulted when the D-Arg PEP was used in combination with pemetrexed against the lung adenocarcinoma cell lines. A xenograft study using the PL-PEP in combination with pemetrexed showed enhanced anti-tumor effects compared to each drug alone.</description><subject>Adenocarcinoma</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Breast cancer</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cisplatin</subject><subject>Deoxyribonucleic acid</subject><subject>Dihydrofolate reductase</subject><subject>DNA</subject><subject>DNA damage</subject><subject>DNA repair</subject><subject>E2F protein</subject><subject>E2F1 protein</subject><subject>Enzymes</subject><subject>Gene amplification</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Lymphoma</subject><subject>Mutation</subject><subject>Non-small cell lung carcinoma</subject><subject>Peptides</subject><subject>Phosphorylation</subject><subject>Prostate</subject><subject>Prostate cancer</subject><subject>Proteins</subject><subject>Small cell lung carcinoma</subject><subject>Solid tumors</subject><subject>Thymidine</subject><subject>Thymidine kinase</subject><subject>Thymidylate synthase</subject><subject>Transcription</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><subject>Xenografts</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkcluFDEQhlsIRKKQc27IEhcONPHWXi5I0WgCkSLBYaIcLW8946jbHuzuAE_C6-Imi5L44l9VX_1VpWqaEwQ_EyLhqdXR-lwQgR2UHL9qDjHkuGVM0tdP9EFzXMoNrI8QxBl_2xwQwjrMKDxs_p7FKbSbeUwZrPve26mA1AMNfvjop6ynEKvcT8F5sNF562tgCzZZx2JzqPEUF36Nz1v0CWCgowNEg4sC1nG3zOfA9c5HcFWqql6rNJoQ9f-6X2HaVfOx9vG_a7qOsAplPyxN3zVvej0Uf3z_HzVX5-vN6lt7-f3rxerssrUUo6kVmBlDJDISI6oxdJpqIQ0T3mLaIywl7bkztKvSOW2EcbgTnGPvhWC4I0fNlzvf_WxG76yPdelB7XMYdf6jkg7qeSaGndqmW8VlxzoCq8HHe4Ocfs6-TGoMxfph0NGnuShMJcOUYygq-uEFepPmHOt6C8UhFVKiSp3eUTanUrLvH4dBUC13Vy_uXiveP93hkX-4MvkHUuiqPQ</recordid><startdate>20210226</startdate><enddate>20210226</enddate><creator>Rather, Gulam Mohmad</creator><creator>Anyanwu, Michael</creator><creator>Minko, Tamara</creator><creator>Garbuzenko, Olga</creator><creator>Szekely, Zoltan</creator><creator>Bertino, Joseph R</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2175-2263</orcidid></search><sort><creationdate>20210226</creationdate><title>Anti-Tumor Effects of a Penetratin Peptide Targeting Transcription of E2F-1, 2 and 3a Is Enhanced When Used in Combination with Pemetrexed or Cisplatin</title><author>Rather, Gulam Mohmad ; Anyanwu, Michael ; Minko, Tamara ; Garbuzenko, Olga ; Szekely, Zoltan ; Bertino, Joseph R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-826bb391b9214a20da4a89b68ec24f12994f7db45129ddab8bd258772ee886253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenocarcinoma</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Breast cancer</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cisplatin</topic><topic>Deoxyribonucleic acid</topic><topic>Dihydrofolate reductase</topic><topic>DNA</topic><topic>DNA damage</topic><topic>DNA repair</topic><topic>E2F protein</topic><topic>E2F1 protein</topic><topic>Enzymes</topic><topic>Gene amplification</topic><topic>Kinases</topic><topic>Lung cancer</topic><topic>Lymphoma</topic><topic>Mutation</topic><topic>Non-small cell lung carcinoma</topic><topic>Peptides</topic><topic>Phosphorylation</topic><topic>Prostate</topic><topic>Prostate cancer</topic><topic>Proteins</topic><topic>Small cell lung carcinoma</topic><topic>Solid tumors</topic><topic>Thymidine</topic><topic>Thymidine kinase</topic><topic>Thymidylate synthase</topic><topic>Transcription</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rather, Gulam Mohmad</creatorcontrib><creatorcontrib>Anyanwu, Michael</creatorcontrib><creatorcontrib>Minko, Tamara</creatorcontrib><creatorcontrib>Garbuzenko, Olga</creatorcontrib><creatorcontrib>Szekely, Zoltan</creatorcontrib><creatorcontrib>Bertino, Joseph R</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Access via ProQuest (Open Access)</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rather, Gulam Mohmad</au><au>Anyanwu, Michael</au><au>Minko, Tamara</au><au>Garbuzenko, Olga</au><au>Szekely, Zoltan</au><au>Bertino, Joseph R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-Tumor Effects of a Penetratin Peptide Targeting Transcription of E2F-1, 2 and 3a Is Enhanced When Used in Combination with Pemetrexed or Cisplatin</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2021-02-26</date><risdate>2021</risdate><volume>13</volume><issue>5</issue><spage>972</spage><pages>972-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>We tested the antitumor effects of a modified E2F peptide substituting D-Arg for L-Arg, conjugated to penetratin (PEP) against solid tumor cell lines and the CCRF-leukemia cell line, alone and in combination with pemetrexed or with cisplatin. For
-
studies, the peptide was encapsulated in PEGylated liposomes (PL-PEP) to increase half-life and stability.
Prostate cancer (DU145 and PC3), breast cancer (MCF7, MDA-MB-468, and 4T1), lymphoma (CCRF-CEM), and non-small cell lung cancer (NSCLC) cell lines (H2009, H441, H1975, and H2228) were treated with D-Arg PEP in combination with cisplatin or pemetrexed. Western blot analysis was performed on the NSCLC for E2F-1, pRb, thymidylate synthase, and thymidine kinase. The H2009 cell line was selected for an
-
study.
When the PEP was combined with cisplatin and tested against solid tumor cell lines and the CCRF-CEM leukemia cell line, there was a modest synergistic effect. A marked synergistic effect was seen when the combination of pemetrexed and the PEP was tested against the adenocarcinoma lung cancer cell lines. The addition of the PEP to pemetrexed enhanced the antitumor effects of pemetrexed in a xenograft of the H2009 in mice.
The D-Arg PEP in combination with cisplatin caused synergistic cell kill against prostate, breast, lung cancers, and the CCRF-CEM cell line. Marked synergy resulted when the D-Arg PEP was used in combination with pemetrexed against the lung adenocarcinoma cell lines. A xenograft study using the PL-PEP in combination with pemetrexed showed enhanced anti-tumor effects compared to each drug alone.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33652640</pmid><doi>10.3390/cancers13050972</doi><orcidid>https://orcid.org/0000-0003-2175-2263</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Adenocarcinoma Antitumor activity Apoptosis Breast cancer Cell cycle Cell growth Cisplatin Deoxyribonucleic acid Dihydrofolate reductase DNA DNA damage DNA repair E2F protein E2F1 protein Enzymes Gene amplification Kinases Lung cancer Lymphoma Mutation Non-small cell lung carcinoma Peptides Phosphorylation Prostate Prostate cancer Proteins Small cell lung carcinoma Solid tumors Thymidine Thymidine kinase Thymidylate synthase Transcription Tumor cell lines Tumors Xenografts |
| title | Anti-Tumor Effects of a Penetratin Peptide Targeting Transcription of E2F-1, 2 and 3a Is Enhanced When Used in Combination with Pemetrexed or Cisplatin |
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