<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0120-0011</journal-id>
<journal-title><![CDATA[Revista de la Facultad de Medicina]]></journal-title>
<abbrev-journal-title><![CDATA[rev.fac.med.]]></abbrev-journal-title>
<issn>0120-0011</issn>
<publisher>
<publisher-name><![CDATA[Universidad Nacional de Colombia]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0120-00112018000400543</article-id>
<article-id pub-id-type="doi">10.15446/revfacmed.v66n4.55149</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Hypoxia-inducible factor HIF-1&#945; modulates drugs resistance in colon cancer cells]]></article-title>
<article-title xml:lang="es"><![CDATA[Factor inducible por hipoxia HIF-1&#945; modula la resistencia a drogas en células de cáncer de colon]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Pinzon-Daza]]></surname>
<given-names><![CDATA[Martha Leonor]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Cuellar]]></surname>
<given-names><![CDATA[Yenith]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ondo]]></surname>
<given-names><![CDATA[Alejandro]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Matheus]]></surname>
<given-names><![CDATA[Luisa]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Riesgo]]></surname>
<given-names><![CDATA[Lilia Del]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Castillo]]></surname>
<given-names><![CDATA[Fabio]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Garzón]]></surname>
<given-names><![CDATA[Ruth]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidad del Rosario  ]]></institution>
<addr-line><![CDATA[Bogotá ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Universidad Nacional de Colombia  ]]></institution>
<addr-line><![CDATA[Bogotá D.C ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Universidad del Rosario  ]]></institution>
<addr-line><![CDATA[Bogotá D.C ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Universidad del Rosario  ]]></institution>
<addr-line><![CDATA[Bogotá D.C ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af5">
<institution><![CDATA[,Universidad del Rosario  ]]></institution>
<addr-line><![CDATA[Bogotá D.C ]]></addr-line>
<country>Colombia</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>12</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>12</month>
<year>2018</year>
</pub-date>
<volume>66</volume>
<numero>4</numero>
<fpage>543</fpage>
<lpage>550</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_arttext&amp;pid=S0120-00112018000400543&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_abstract&amp;pid=S0120-00112018000400543&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_pdf&amp;pid=S0120-00112018000400543&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract  Introduction: Drug resistance mechanisms may be associated with decreased cell death and its induction may depend on the response to oxidative stress caused by hypoxia. The correlation between hypoxia-inducible factor HIF-1&#945;, the number of reactive oxygen species and their effect on cell survival has not yet been evaluated.  Objective: The purpose of this study was to evaluate the effect of HIF-1&#945; activity and reactive oxygen species (ROS) accumulation in apoptosis of colon cancer cells.  Materials and methods: HT29 colon cancer cells were treated with Cobalt(II) chloride (CoCl2) or doxorubicin and the activity of HIF-1&#945; was determined by ELISA assay. ROS were determined using fluorescence probe carboxy-H2DFFDA. Apoptosis was assessed by caspase-3 activation analysis, and PUMA and BAX mRNA levels by qRT-PCR. The reduction of the antiapoptotic effect due to hypoxia was attenuated by use of the endonuclease APE-1 (E3330) inhibitor. The endonuclease E3330 APE-1 inhibitor allowed evaluating the effect of ROS generated by doxorubicin and CoCl2 on apoptosis.  Results: Chemical hypoxia in combination with doxorubicin is an oxidative stressor in HT29 cells and induces a reduction in the apoptotic process in a time-dependent manner.  Conclusion: Resistance to hypoxia and doxorubicin-mediated cell death could be controlled by a mechanism related to the activity of HIF-1&#945; and the amount of reactive oxygen species generated.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen  Introducción. Los mecanismos de resistencia a drogas podrían asociarse con disminución en la muerte celular y su inducción podría depender de la respuesta al estrés oxidativo que origina la hipoxia. La correlación entre factor inducible por hipoxia HIF-1&#945;, cantidad de especies reactivas de oxígeno y su efecto sobre la supervivencia celular aún no ha sido evaluada.  Objetivo. Evaluar el efecto de la inducción de la actividad de HIF-1&#945; y la cantidad de especies reactivas de oxígeno sobre la apoptosis en células de cáncer de colon.  Materiales y métodos. Células de cáncer de colon HT29 fueron tratadas con cloruro de cobalto (CoCl2) o doxorrubicina; la actividad de HIF-1&#945; se evaluó por ELISA. Las especies reactivas de oxígeno fueron determinadas con sonda fluorescente carboxi-H2DFFDA. La apoptosis fue evaluada por la actividad de caspasa-3 y los niveles de mRNA de los genes proapoptóticos PUMA y BAX por qRT-PCR. El inhibidor de la endonucleasa APE-1 E3330 permitió evaluar el efecto de las especies reactivas de oxígeno generadas por doxorubicina y CoCl2 sobre la apoptosis.  Resultados. La hipoxia química combinada + doxorubicina es estresor oxidativo en células HT29 e induce una reducción en el proceso apoptótico de manera tiempo dependiente.  Conclusión. La resistencia a la muerte celular mediada por hipoxia y doxorubicina podría estar controlada por un mecanismo relacionado con la actividad de HIF-1&#945; y la cantidad de especies reactivas de oxígeno generadas.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Apoptosis]]></kwd>
<kwd lng="en"><![CDATA[Cell Hypoxia]]></kwd>
<kwd lng="en"><![CDATA[Colon Cancer]]></kwd>
<kwd lng="en"><![CDATA[Doxorubicin (MeSH)]]></kwd>
<kwd lng="es"><![CDATA[Apoptosis]]></kwd>
<kwd lng="es"><![CDATA[Hipoxia celular]]></kwd>
<kwd lng="es"><![CDATA[Cáncer del colon]]></kwd>
<kwd lng="es"><![CDATA[Doxorrubicina (DeCS)]]></kwd>
</kwd-group>
</article-meta>
</front><back>
<ref-list>
<ref id="B1">
<label>1</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Conklin]]></surname>
<given-names><![CDATA[KA]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness]]></article-title>
<source><![CDATA[Integr Cancer Ther]]></source>
<year>2004</year>
<volume>3</volume>
<page-range>294-300</page-range></nlm-citation>
</ref>
<ref id="B2">
<label>2</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Chen]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Reactive Oxygen Species and Drug Resistance in Cancer Chemotherapy]]></article-title>
<source><![CDATA[Austin J Clin Pathol]]></source>
<year>2014</year>
<volume>1</volume>
<numero>4</numero>
<issue>4</issue>
<page-range>1-7</page-range></nlm-citation>
</ref>
<ref id="B3">
<label>3</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Pauwels]]></surname>
<given-names><![CDATA[EK]]></given-names>
</name>
<name>
<surname><![CDATA[Erba]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Mariani]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Gomes]]></surname>
<given-names><![CDATA[CM]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Multidrug resistance in cancer: its mechanism and its modulation]]></article-title>
<source><![CDATA[Drug News Perspect]]></source>
<year>2007</year>
<volume>20</volume>
<numero>6</numero>
<issue>6</issue>
<page-range>371-7</page-range></nlm-citation>
</ref>
<ref id="B4">
<label>4</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Chandel]]></surname>
<given-names><![CDATA[NS]]></given-names>
</name>
<name>
<surname><![CDATA[McClintock]]></surname>
<given-names><![CDATA[DS]]></given-names>
</name>
<name>
<surname><![CDATA[Feliciano]]></surname>
<given-names><![CDATA[CE]]></given-names>
</name>
<name>
<surname><![CDATA[Wood]]></surname>
<given-names><![CDATA[TM]]></given-names>
</name>
<name>
<surname><![CDATA[Melendez]]></surname>
<given-names><![CDATA[JA]]></given-names>
</name>
<name>
<surname><![CDATA[Rodriguez]]></surname>
<given-names><![CDATA[AM]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing]]></article-title>
<source><![CDATA[J Biol Chem]]></source>
<year>2000</year>
<volume>275</volume>
<numero>33</numero>
<issue>33</issue>
<page-range>25130-8</page-range></nlm-citation>
</ref>
<ref id="B5">
<label>5</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Brunelle]]></surname>
<given-names><![CDATA[JK]]></given-names>
</name>
<name>
<surname><![CDATA[Bell]]></surname>
<given-names><![CDATA[EL]]></given-names>
</name>
<name>
<surname><![CDATA[Quesada]]></surname>
<given-names><![CDATA[NM]]></given-names>
</name>
<name>
<surname><![CDATA[Vercauteren]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Tiranti]]></surname>
<given-names><![CDATA[V]]></given-names>
</name>
<name>
<surname><![CDATA[Zeviani]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation]]></article-title>
<source><![CDATA[Cell Metab]]></source>
<year>2005</year>
<volume>1</volume>
<numero>6</numero>
<issue>6</issue>
<page-range>409-14</page-range></nlm-citation>
</ref>
<ref id="B6">
<label>6</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Guzy]]></surname>
<given-names><![CDATA[RD]]></given-names>
</name>
<name>
<surname><![CDATA[Hoyos]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Robin]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
<name>
<surname><![CDATA[Chen]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Liu]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Mansfield]]></surname>
<given-names><![CDATA[KD]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing]]></article-title>
<source><![CDATA[Cell Metab]]></source>
<year>2005</year>
<volume>1</volume>
<numero>6</numero>
<issue>6</issue>
<page-range>401-8</page-range></nlm-citation>
</ref>
<ref id="B7">
<label>7</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Qutub]]></surname>
<given-names><![CDATA[AA]]></given-names>
</name>
<name>
<surname><![CDATA[Popel]]></surname>
<given-names><![CDATA[AS]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Reactive oxygen species regulate hypoxia-inducible factor 1alpha differentially in cancer and ischemia]]></article-title>
<source><![CDATA[Mol Cell Biol]]></source>
<year>2008</year>
<volume>28</volume>
<numero>16</numero>
<issue>16</issue>
<page-range>5106-19</page-range></nlm-citation>
</ref>
<ref id="B8">
<label>8</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Hagen]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Oxygen versus reactive oxygen in the regulation of HIF-1&#945;: the balance tips]]></article-title>
<source><![CDATA[Biochem Res Int]]></source>
<year>2012</year>
<volume>2012</volume>
</nlm-citation>
</ref>
<ref id="B9">
<label>9</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Haar]]></surname>
<given-names><![CDATA[CP]]></given-names>
</name>
<name>
<surname><![CDATA[Hebbar]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Wallace]]></surname>
<given-names><![CDATA[GC]]></given-names>
</name>
<name>
<surname><![CDATA[Das]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Vandergrift]]></surname>
<given-names><![CDATA[WA]]></given-names>
</name>
<name>
<surname><![CDATA[Smith]]></surname>
<given-names><![CDATA[JA]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Drug resistance in glioblastoma: a mini review]]></article-title>
<source><![CDATA[Neurochem Res]]></source>
<year>2012</year>
<volume>37</volume>
<numero>6</numero>
<issue>6</issue>
<page-range>1192-200</page-range></nlm-citation>
</ref>
<ref id="B10">
<label>10</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Erler]]></surname>
<given-names><![CDATA[JT]]></given-names>
</name>
<name>
<surname><![CDATA[Cawthorne]]></surname>
<given-names><![CDATA[CJ]]></given-names>
</name>
<name>
<surname><![CDATA[Williams]]></surname>
<given-names><![CDATA[KJ]]></given-names>
</name>
<name>
<surname><![CDATA[Koritzinsky]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Wouters]]></surname>
<given-names><![CDATA[BG]]></given-names>
</name>
<name>
<surname><![CDATA[Wilson]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Hypoxia-mediated down-regulation of Bid and BAX in tumors occurs via hypoxia-inducible factor 1-dependent and -independent mechanisms and contributes to drug resistance]]></article-title>
<source><![CDATA[Mol Cell Biol]]></source>
<year>2004</year>
<volume>24</volume>
<numero>7</numero>
<issue>7</issue>
<page-range>2875-89</page-range></nlm-citation>
</ref>
<ref id="B11">
<label>11</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Thorn]]></surname>
<given-names><![CDATA[CF]]></given-names>
</name>
<name>
<surname><![CDATA[Oshiro]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Sh]]></surname>
<given-names><![CDATA[Marsh]]></given-names>
</name>
<name>
<surname><![CDATA[Hernandez-Boussard]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[McLeod]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Klein]]></surname>
<given-names><![CDATA[TE]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Doxorubicin pathways: pharmacodynamics and adverse effects]]></article-title>
<source><![CDATA[Pharmacogenet Genomics]]></source>
<year>2012</year>
<volume>21</volume>
<numero>7</numero>
<issue>7</issue>
<page-range>440-6</page-range></nlm-citation>
</ref>
<ref id="B12">
<label>12</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Wei]]></surname>
<given-names><![CDATA[MC]]></given-names>
</name>
<name>
<surname><![CDATA[Zong]]></surname>
<given-names><![CDATA[WX]]></given-names>
</name>
<name>
<surname><![CDATA[Cheng]]></surname>
<given-names><![CDATA[EH]]></given-names>
</name>
<name>
<surname><![CDATA[Lindsten]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
<name>
<surname><![CDATA[Panoutsakopoulou]]></surname>
<given-names><![CDATA[V]]></given-names>
</name>
<name>
<surname><![CDATA[Ross]]></surname>
<given-names><![CDATA[AJ]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Proapoptotic Bax and Bak: A requisite gateway to mitochondrial dysfunction and death]]></article-title>
<source><![CDATA[Science]]></source>
<year>2001</year>
<volume>292</volume>
<numero>5527</numero>
<issue>5527</issue>
<page-range>727-30</page-range></nlm-citation>
</ref>
<ref id="B13">
<label>13</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Yu]]></surname>
<given-names><![CDATA[JQ]]></given-names>
</name>
<name>
<surname><![CDATA[Liu]]></surname>
<given-names><![CDATA[HB]]></given-names>
</name>
<name>
<surname><![CDATA[Tian]]></surname>
<given-names><![CDATA[DZ]]></given-names>
</name>
<name>
<surname><![CDATA[Liu]]></surname>
<given-names><![CDATA[YW]]></given-names>
</name>
<name>
<surname><![CDATA[Lei]]></surname>
<given-names><![CDATA[JC]]></given-names>
</name>
<name>
<surname><![CDATA[Zou]]></surname>
<given-names><![CDATA[GL]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Changes in mitochondrial membrane potential and reactive oxygen species during wogonin-induced cell death in human hepatoma cells]]></article-title>
<source><![CDATA[Hepatol Res]]></source>
<year>2007</year>
<volume>37</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>68-76</page-range></nlm-citation>
</ref>
<ref id="B14">
<label>14</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Hao]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Dong]]></surname>
<given-names><![CDATA[Y]]></given-names>
</name>
<name>
<surname><![CDATA[Bowling]]></surname>
<given-names><![CDATA[MT]]></given-names>
</name>
<name>
<surname><![CDATA[Gomez-Gutierrez]]></surname>
<given-names><![CDATA[JG]]></given-names>
</name>
<name>
<surname><![CDATA[Zhou]]></surname>
<given-names><![CDATA[HS]]></given-names>
</name>
<name>
<surname><![CDATA[McMasters]]></surname>
<given-names><![CDATA[KM]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation]]></article-title>
<source><![CDATA[BMC Cancer]]></source>
<year>2007</year>
<volume>7</volume>
<page-range>24</page-range></nlm-citation>
</ref>
<ref id="B15">
<label>15</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Ling]]></surname>
<given-names><![CDATA[LU]]></given-names>
</name>
<name>
<surname><![CDATA[Tan]]></surname>
<given-names><![CDATA[KB]]></given-names>
</name>
<name>
<surname><![CDATA[Lin]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Chiu]]></surname>
<given-names><![CDATA[GN]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The role of reactive oxygen species and autophagy in safingol-induced cell death]]></article-title>
<source><![CDATA[Cell Death Dis]]></source>
<year>2011</year>
<volume>2</volume>
</nlm-citation>
</ref>
<ref id="B16">
<label>16</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Brauns]]></surname>
<given-names><![CDATA[SC]]></given-names>
</name>
<name>
<surname><![CDATA[Dealtry]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Milne]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Naudé]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Van De Venter]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Caspase-3 activation and induction of PARP cleavage by cyclic dipeptide cyclo(Phe-Pro) in HT-29 cells]]></article-title>
<source><![CDATA[Anticancer Res]]></source>
<year>2005</year>
<volume>25</volume>
<numero>6B</numero>
<issue>6B</issue>
<page-range>4197-202</page-range></nlm-citation>
</ref>
<ref id="B17">
<label>17</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Luo]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Delaplane]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Jiang]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Reed]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[He]]></surname>
<given-names><![CDATA[Y]]></given-names>
</name>
<name>
<surname><![CDATA[Fishel]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Role of the multifunctional DNA repair and redox signaling protein Ape1/Ref-1 in cancer and endothelial cells: small-molecule inhibition of the redox function of Ape1]]></article-title>
<source><![CDATA[Antioxid Redox Signal]]></source>
<year>2008</year>
<volume>10</volume>
<numero>11</numero>
<issue>11</issue>
<page-range>1853-67</page-range></nlm-citation>
</ref>
<ref id="B18">
<label>18</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Maiti]]></surname>
<given-names><![CDATA[AK]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Reactive Oxygen Species Reduction is a Key Underlying Mechanism of Drug Resistance in Cancer Chemotherapy]]></article-title>
<source><![CDATA[Chemotherapy]]></source>
<year>2012</year>
<volume>1</volume>
<numero>2</numero>
<issue>2</issue>
</nlm-citation>
</ref>
<ref id="B19">
<label>19</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Comerford]]></surname>
<given-names><![CDATA[KM]]></given-names>
</name>
<name>
<surname><![CDATA[Wallace]]></surname>
<given-names><![CDATA[TJ]]></given-names>
</name>
<name>
<surname><![CDATA[Karhausen]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Louis]]></surname>
<given-names><![CDATA[NA]]></given-names>
</name>
<name>
<surname><![CDATA[Montalto]]></surname>
<given-names><![CDATA[MC]]></given-names>
</name>
<name>
<surname><![CDATA[Colgan]]></surname>
<given-names><![CDATA[SP]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Hypoxia-inducible Factor-1-dependent Regulation of the Multidrug Resistance (MDR1) Gene]]></article-title>
<source><![CDATA[Cancer Res]]></source>
<year>2002</year>
<volume>62</volume>
<numero>12</numero>
<issue>12</issue>
<page-range>3387-94</page-range></nlm-citation>
</ref>
<ref id="B20">
<label>20</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Semenza]]></surname>
<given-names><![CDATA[GL]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Life with oxygen]]></article-title>
<source><![CDATA[Science]]></source>
<year>2007</year>
<volume>318</volume>
<numero>5847</numero>
<issue>5847</issue>
<page-range>62-4</page-range></nlm-citation>
</ref>
<ref id="B21">
<label>21</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Chuu]]></surname>
<given-names><![CDATA[JJ]]></given-names>
</name>
<name>
<surname><![CDATA[Liu]]></surname>
<given-names><![CDATA[JM]]></given-names>
</name>
<name>
<surname><![CDATA[Tsou]]></surname>
<given-names><![CDATA[MH]]></given-names>
</name>
<name>
<surname><![CDATA[Huang]]></surname>
<given-names><![CDATA[CL]]></given-names>
</name>
<name>
<surname><![CDATA[Chen]]></surname>
<given-names><![CDATA[CP]]></given-names>
</name>
<name>
<surname><![CDATA[Wang]]></surname>
<given-names><![CDATA[HS]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Effects of paclitaxel and doxorubicin in histocultures of hepatocelular carcinomas]]></article-title>
<source><![CDATA[J Biomed Sci]]></source>
<year>2007</year>
<volume>14</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>233-44</page-range></nlm-citation>
</ref>
<ref id="B22">
<label>22</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Sutter]]></surname>
<given-names><![CDATA[AP]]></given-names>
</name>
<name>
<surname><![CDATA[Maaser]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Grabowski]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Bradacs]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Vormbrock]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Hopfner]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Peripheral benzodiazepine receptor ligands induce apoptosis and cell cycle arrest in human hepatocellular carcinoma cells and enhance chemosensitivity to paclitaxel, docetaxel, doxorubicin and the Bcl-2 inhibitor HA14-1]]></article-title>
<source><![CDATA[J Hepatol]]></source>
<year>2004</year>
<volume>41</volume>
<numero>5</numero>
<issue>5</issue>
<page-range>799-807</page-range></nlm-citation>
</ref>
<ref id="B23">
<label>23</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Burkitt]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Chun]]></surname>
<given-names><![CDATA[SY]]></given-names>
</name>
<name>
<surname><![CDATA[Dang]]></surname>
<given-names><![CDATA[DT]]></given-names>
</name>
<name>
<surname><![CDATA[Dang]]></surname>
<given-names><![CDATA[LH]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Targeting both HIF-1 and HIF-2 in human colon cancer cells improves tumor response to sunitinib treatment]]></article-title>
<source><![CDATA[Mol Cancer Ther]]></source>
<year>2009</year>
<volume>8</volume>
<numero>5</numero>
<issue>5</issue>
<page-range>1148-56</page-range></nlm-citation>
</ref>
<ref id="B24">
<label>24</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Puppo]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Battaglia]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[Ottaviano]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Delfino]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Ribatti]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Varesio]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Topotecan inhibits vascular endothelial growth factor production and angiogenic activity induced by hypoxia in human neuroblastoma by targeting hypoxia-inducible factor-1alpha and -2alpha]]></article-title>
<source><![CDATA[Mol Cancer Ther]]></source>
<year>2008</year>
<volume>7</volume>
<numero>7</numero>
<issue>7</issue>
<page-range>1974-84</page-range></nlm-citation>
</ref>
<ref id="B25">
<label>25</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Liu]]></surname>
<given-names><![CDATA[Z]]></given-names>
</name>
<name>
<surname><![CDATA[Lu]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Shi]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Du]]></surname>
<given-names><![CDATA[Y]]></given-names>
</name>
<name>
<surname><![CDATA[Yu]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Gu]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[PUMA overexpression induces reactive oxygen species generation and proteasome-mediated stathmin degradation in colorectal cancer cells]]></article-title>
<source><![CDATA[Cancer Res]]></source>
<year>2005</year>
<volume>65</volume>
<numero>5</numero>
<issue>5</issue>
<page-range>1647-54</page-range></nlm-citation>
</ref>
<ref id="B26">
<label>26</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Liu]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Wang]]></surname>
<given-names><![CDATA[Z]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Increased Oxidative Stress as a Selective Anticancer Therapy]]></article-title>
<source><![CDATA[Oxid Med Cell Longev]]></source>
<year>2015</year>
<volume>2015</volume>
<page-range>294303</page-range></nlm-citation>
</ref>
<ref id="B27">
<label>27</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Zhou]]></surname>
<given-names><![CDATA[CH]]></given-names>
</name>
<name>
<surname><![CDATA[Zhang]]></surname>
<given-names><![CDATA[XP]]></given-names>
</name>
<name>
<surname><![CDATA[Liu]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[Wang]]></surname>
<given-names><![CDATA[W]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Modeling the interplay between the HIF-1 and p53 pathways in hypoxia]]></article-title>
<source><![CDATA[Sci Rep]]></source>
<year>2015</year>
<volume>5</volume>
<page-range>13834</page-range></nlm-citation>
</ref>
<ref id="B28">
<label>28</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Yu]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Zhang]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[PUMA, a potent killer with or without p53]]></article-title>
<source><![CDATA[Oncogene]]></source>
<year>2008</year>
<volume>27</volume>
<numero>^sSuppl 1</numero>
<issue>^sSuppl 1</issue>
<supplement>Suppl 1</supplement>
<page-range>S71-83</page-range></nlm-citation>
</ref>
<ref id="B29">
<label>29</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Yu]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Wang]]></surname>
<given-names><![CDATA[Z]]></given-names>
</name>
<name>
<surname><![CDATA[Kinzler]]></surname>
<given-names><![CDATA[KW]]></given-names>
</name>
<name>
<surname><![CDATA[Vogelstein]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Zhang]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[PUMA mediates the apoptotic response to p53 in colorectal cancer cells]]></article-title>
<source><![CDATA[Proc Natl Acad Sci USA]]></source>
<year>2003</year>
<volume>100</volume>
<numero>4</numero>
<issue>4</issue>
<page-range>1931-6</page-range></nlm-citation>
</ref>
<ref id="B30">
<label>30</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Jacobsen]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Honecker]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Cisplatin resistance in germ cell tumours: models and mechanisms]]></article-title>
<source><![CDATA[Andrology]]></source>
<year>2015</year>
<volume>3</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>111-21</page-range></nlm-citation>
</ref>
<ref id="B31">
<label>31</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Tell]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Quadrifoglio]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[Tiribelli]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Kelley]]></surname>
<given-names><![CDATA[MR]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The Many Functions of APEl/Ref-l: Not Only a DNA Repair Enzyme]]></article-title>
<source><![CDATA[Antioxid Redox Signal]]></source>
<year>2009</year>
<volume>11</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>601-19</page-range></nlm-citation>
</ref>
<ref id="B32">
<label>32</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Kelley]]></surname>
<given-names><![CDATA[MR]]></given-names>
</name>
<name>
<surname><![CDATA[Georgiadis]]></surname>
<given-names><![CDATA[MM]]></given-names>
</name>
<name>
<surname><![CDATA[Fishel]]></surname>
<given-names><![CDATA[ML]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[APE1/Ref-1 role in redox signaling: translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1]]></article-title>
<source><![CDATA[Curr Mol Pharmacol]]></source>
<year>2012</year>
<volume>5</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>36-53</page-range></nlm-citation>
</ref>
<ref id="B33">
<label>33</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Luo]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[He]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Kelley]]></surname>
<given-names><![CDATA[MR]]></given-names>
</name>
<name>
<surname><![CDATA[Georgiadis]]></surname>
<given-names><![CDATA[MM]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Redox regulation of DNA repair: implications for human health and cancer therapeutic development]]></article-title>
<source><![CDATA[Antioxid Redox Signal]]></source>
<year>2010</year>
<volume>12</volume>
<numero>11</numero>
<issue>11</issue>
<page-range>1247-69</page-range></nlm-citation>
</ref>
<ref id="B34">
<label>34</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Wang]]></surname>
<given-names><![CDATA[X]]></given-names>
</name>
<name>
<surname><![CDATA[Wang]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Lin]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Geng]]></surname>
<given-names><![CDATA[Y]]></given-names>
</name>
<name>
<surname><![CDATA[Wang]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Jiang]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Sp1 is involved in H2O2-induced PUMA gene expression and apoptosis in colorectal cancer cells]]></article-title>
<source><![CDATA[J Exp Clin Cancer Res]]></source>
<year>2008</year>
<volume>27</volume>
<numero>44</numero>
<issue>44</issue>
</nlm-citation>
</ref>
<ref id="B35">
<label>35</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[You]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Pellegrini]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Tsuchihara]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Yamamoto]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Hacker]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Erlacher]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[FOXO3a-dependent regulation of PUMA in response to cytokine/growth factor withdrawal]]></article-title>
<source><![CDATA[J Exp Med]]></source>
<year>2006</year>
<volume>203</volume>
<numero>7</numero>
<issue>7</issue>
<page-range>1657-63</page-range></nlm-citation>
</ref>
<ref id="B36">
<label>36</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Ambacher]]></surname>
<given-names><![CDATA[KK]]></given-names>
</name>
<name>
<surname><![CDATA[Pitzul]]></surname>
<given-names><![CDATA[KB]]></given-names>
</name>
<name>
<surname><![CDATA[Karajgikar]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Hamilton]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Ferguson]]></surname>
<given-names><![CDATA[SS]]></given-names>
</name>
<name>
<surname><![CDATA[Cregan]]></surname>
<given-names><![CDATA[SP]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The JNK- and AKT/GSK3p- signaling pathways converge to regulate PUMA induction and neuronal apoptosis induced by trophic factor deprivation]]></article-title>
<source><![CDATA[PLoS One]]></source>
<year>2012</year>
<volume>7</volume>
<numero>10</numero>
<issue>10</issue>
</nlm-citation>
</ref>
</ref-list>
</back>
</article>
