Survivin expression is an independent prognostic factor in rectal cancer patients with and without preoperative radiotherapy

Knutsen, Annica; Adell, Gunnar; Sun, Xiao‐Feng

doi:10.1016/j.ijrobp.2004.02.007

Cited by 51 publications

(36 citation statements)

References 17 publications

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“…In our previous study on the surgical material used in the present study no relationship was seen between p73 expression [19] and the expression of p53 [20] and survivin [21], however recently a possible relationship between p53, p73 and survivin has been seen [32][33][34]. Wild type p53, but not mutated p53 seems to repress survivin, either transcriptionally via E2F1 or via acetylation of the promoter region of survivin, containing two p53 binding elements [32,34].…”

Section: Discussioncontrasting

confidence: 47%

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Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival in rectal cancer patients with or without preoperative radiotherapy

Lööf

Pfeifer

Adell

et al. 2009

Radiotherapy and Oncology

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Section: Discussioncontrasting

confidence: 47%

“…The data regarding the expression of p73 [19], p53 [20] and survivin [21], on the same surgical material from both the non-radiotherapy and radiotherapy groups as used in the present study (not biopsies), were taken from previous studies performed at our laboratory.…”

Section: Immunohistochemistry Of P73 P53 and Survivinmentioning

confidence: 99%

Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival in rectal cancer patients with or without preoperative radiotherapy

Lööf

Pfeifer

Adell

et al. 2009

Radiotherapy and Oncology

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“…In vitro studies, using colorectal cancer cell lines with different intrinsic radiosensitivities further confirmed that spontaneous and radiation-induced apoptosis correlated closely with radiation response (7). Although it is clear from the literature that apoptosis propensity may be regulated by various factors, including p53 and the bcl-2 family, a prominent role of survivin, a structurally unique member of the inhibitor of apoptosis family (8)(9)(10), has recently been shown for colorectal cancer tumorigenesis and prognosis (11)(12)(13)(14)(15)(16). In a panel of colorectal cell lines, we have previously shown an inverse relationship between levels of survivin expression, rates of spontaneous and radiation-induced apoptosis, and radiosensitivity as determined by the clonogenic assay (7).…”

Section: Introductionmentioning

confidence: 74%

“…In colorectal cancer, the immunohistochemically determined expression of survivin protein correlated with decreased apoptosis, increased proliferation, increased angiogenesis, and, consequently, unfavorable prognosis (11,(13)(14)(15)(16)(17)(18). Microarray-based gene profiling studies recently identified survivin as a ''risk-associated'' gene signature for unfavorable outcome in this disease (19,20).…”

Section: Discussionmentioning

confidence: 99%

Survivin as a Radioresistance Factor, and Prognostic and Therapeutic Target for Radiotherapy in Rectal Cancer

et al. 2005

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Apoptosis levels have been shown to predict tumor response to preoperative radiochemotherapy in rectal cancer. Recently, the prominent role of survivin, a structurally unique member of the inhibitor of apoptosis protein family, has been shown in colorectal cancer tumorigenesis and prognosis. In this study, we investigated whether survivin plays a direct role in mediating radiation resistance. We used short interfering RNA molecules to decrease survivin in radioresistant SW480 and intermediately radioresistant HCT-15 colorectal cancer cells. This resulted in a significant decrease of survivin mRNA and protein expression with a maximum at 24 to 48 hours after transfection. If irradiated during this sensitive period, an increased percentage of apoptotic cells and an increased caspase 3/7 activity in parallel with a decreased cell viability and a reduced clonogenic survival was shown. These effects were more pronounced in the radioresistant SW480 cell line with a radiation-induced cytotoxicity enhancement factor at 10% and 50% survival of 1.8 to 2.2 for SW480 and 1.5 to 1.7 for HCT-15, respectively. Furthermore, transfection with survivin short interfering RNA increased levels of G 2 -M arrest and levels of DNA double-strand breaks in irradiated cells. These observations indicate that cell cycle and DNA repair mechanisms may be associated with apoptosis induction in tumor cells that are otherwise resistant to killing by radiation. In a translational study of 59 patients with rectal cancer treated with a combination of radiotherapy and chemotherapy, increased survivin expression was inversely related to the levels of apoptosis, and was also associated with a significantly higher risk of a local tumor recurrence. (Cancer Res 2005; 65(11): 4881-7)

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“…After being washed in PBS, the sections were incubated with protein block (Dako) for 10 minutes to reduce nonspecific background staining. The sections were incubated with the anti-LOX polyclonal rabbit antibody (synthesized by OpenBiosystems which targets a conserved peptide sequence from the active site of human and mouse proteins and has been shown not to bind other LOX family members [35]) in a 1:50 dilution with antibody diluent buffer overnight. After being washed in PBS, the sections were incubated with a secondary antibody, Envision System Labelled Polymer-HRP AntiRabbit (Dako) for 25 minutes.…”

Section: Ihcmentioning

confidence: 99%

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2017

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Emerging evidence has implicated a pivotal role for lysyl oxidase (LOX) in cancer progression and metastasis. Whilst the majority of work has focused on the extracellular matrix cross-linking role of LOX, the exact function of intracellular LOX localisation remains unclear. In this study, we analysed the LOX expression patterns in the nuclei of rectal cancer patient samples and determined the clinical significance of this expression. Nuclear LOX expression was significantly increased in patient lymph node metastases compared to their primary tumours. High nuclear LOX expression in tumours was correlated with a high rate of distant metastasis and increased recurrence. Multivariable analysis showed that high nuclear LOX expression was also correlated with poor overall survival and disease free survival. Furthermore, we are the first to identify LOX enzyme isoforms (50 kDa and 32 kDa) within the nucleus of colon cancer cell lines by confocal microscopy and Western blot. Our results show a powerful link between nuclear LOX expression in tumours and patient survival, and offer a promising prognostic biomarker for rectal cancer patients.

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Survivin expression is an independent prognostic factor in rectal cancer patients with and without preoperative radiotherapy

Cited by 51 publications

References 17 publications

Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival in rectal cancer patients with or without preoperative radiotherapy

Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival in rectal cancer patients with or without preoperative radiotherapy

Survivin as a Radioresistance Factor, and Prognostic and Therapeutic Target for Radiotherapy in Rectal Cancer

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