title: [Impact of preoperative drug therapy on the expression of apoptosis markers in colorectal liver metastases].
abstract: OBJECTIVE
  to estimate the expression of p53 protein, effector caspases-3 and -7, and the antiapoptotic protein survivin in colorectal adenocarcinoma metastases to the liver in patients who have received preoperative cytotoxic and combined cytotoxic and target anti-VEGF therapies.
  
  
  METHODS
  Intraoperative samples from 122 patients with colorectal carcinoma metastases to the liver were immunohistologically examined. The investigation included patients who had received preoperative treatment with cytotoxic drugs, combined cytotoxic and targeted anti-VEGF therapy. A control group consisted of patients who had not received preoperative anti-tumor drug treatment.
  
  
  RESULTS
  Expression of Caspase 3, including that of survivin, was significantly more frequently detected in the patients who had received combined cytotoxic and anti-VEGF therapy as compared to both those treated with only cytotoxic agents (p=0.00004) and the control group (p=0.0008) As compared to the latter, the women who had received cytotoxic therapy were found to have no survivin expression (p=0.015). Investigation of the expression of caspase-7 and p53 revealed no statistically significant differences between the three groups.
  
  
  CONCLUSIONS
  Addition of bevacizumab to preoperative standard therapy regimens for colorectal adenocarcinoma metastases to the liver leads to activated apoptosis in tumor cells, by enhancing the expression of effector caspase 3. At the same time, standard cytotoxic chemotherapy regimens in women results in activated apoptosis, by decreasing the expression of the antiapoptotic protein survivin.
authors.affiliation: Academician B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia; Research Institute of Human Morphology, Moscow, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Varlamov
authors.affiliation: Academician B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia.
authors.forename: E M
authors.initials: EM
authors.lastname: Paltseva
authors.affiliation: Academician B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia.
authors.forename: M I
authors.initials: MI
authors.lastname: Sekacheva
authors.affiliation: Academician B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia.
authors.forename: D N
authors.initials: DN
authors.lastname: Fedorov
authors.affiliation: Academician B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia.
authors.forename: O G
authors.initials: OG
authors.lastname: Skipenko
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D000068258:Bevacizumab / Q000008:administration & dosage; D053148:Caspase 3 / Q000096:biosynthesis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis* / Q000235:genetics; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D057234:Preoperative Period; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D053148:Caspase 3