An apoptotic molecular network identified by microarray: On the TRAIL to new insights in epithelial ovarian cancer

Ouellet, Véronique; Page, Cécile Le; Madore, Jason; Guyot, Marie-Claude; Barrès, Véronique; Lussier, Christian; Tonin, Patricia N.; Provencher, Diane; Mes-Masson, Anne-Marie

doi:10.1002/cncr.22812

Cited by 18 publications

(26 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The contribution of c-FLIP L expression in identifying patients that do not yet display p53 nuclear accumulation supports a role for this molecule at the tumor onset, while p53 overexpression is apparently more related to later stages of the disease. Consistent with our finding, other authors (Horak et al 2005, Ouellet et al 2007, by studying deregulation of TRAIL cascade in EOC patients, identified c-FLIP L mainly expressed in early-stage ovarian cancer further suggesting that this survival factor is expressed by tumor cells when other mechanisms of apoptosis resistance, like loss of p53 function, are not yet present.…”

Section: Discussionsupporting

confidence: 92%

c-FLIPL expression defines two ovarian cancer patient subsets and is a prognostic factor of adverse outcome

Bagnoli¹,

Ambrogi²,

Pilotti³

et al. 2009

Endocrine-Related Cancer

View full text Add to dashboard Cite

The impairment of apoptotic pathways represents an efficient mechanism to promote chemoresistance in cancer cells. We previously showed that in epithelial ovarian cancer (EOC) cells, long isoform of cellular FLICE-inhibitory protein (c-FLIP L ) accounts for apoptosis resistance in a context of functional p53 and resistance could be overcome by c-FLIP L downmodulation. Here, we studied the association between c-FLIP L and p53 expressions and their prognostic impact in EOC patients. Tumor tissue from 207 patients diagnosed with primary EOC was analyzed by immunohistochemistry (IHC) for c-FLIP L and p53 expressions, and multiple correspondence analysis (MCA) was used to evaluate the multivariable pattern of association among patients' clinical-pathological characteristics and biological determinants. IHC revealed c-FLIP L expression and p53 nuclear accumulation inversely related (PZ0.0001; odds ratioZ0.29, confidence interval (CI)Z0.15-0.055). MCA indicated that p53 accumulation was associated to clinical-pathological variables, while c-FLIP L expression contributed to the overall association pattern independently from other's clinical characteristics and complementary to p53. Kaplan-Meier curves showed a reduced survival time according to c-FLIP L expression in concert with p53 accumulation (median overall survival (OS): 35 months) compared with lack of expression of both markers (median OS: 110 months; log-rank test, P valueZ0.024). The multivariable Cox regression model, adjusted for known prognostic factors, identified c-FLIP L expression, but not p53 nuclear accumulation, as an independent prognostic factor for adverse outcome (hazard ratioZ1.82, 95% CIZ1.17-2.82; PZ0.008). Altogether these data support the independent contribution of c-FLIP L in refining the prognostic information obtained from standard clinical-pathological indicators, confirming its pivotal role in promoting cell survival.

show abstract

Section: Discussionsupporting

confidence: 92%

c-FLIPL expression defines two ovarian cancer patient subsets and is a prognostic factor of adverse outcome

Bagnoli¹,

Ambrogi²,

Pilotti³

et al. 2009

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Drug-induced DR5 up-regulation is more frequently reported than DR4 up-regulation (22,27,31). Several other studies have reported the important role of DR5 in ovarian cancer (12,13). Moreover, in ovarian cancer specimens obtained before and after cisplatin treatment, DR5 expression increased from 37% to 74% after chemotherapy, whereas DR4 staining remained unaltered (32).…”

Section: Discussionmentioning

confidence: 80%

“…The role of DR5 has been implied in ovarian cancer, because hypermethylation of the DR4 promoter and reduced expression of DR4 frequently occur in ovarian cancers (12). Moreover, univariate analysis showed an association for high DR5 expression with decreased survival in ovarian cancers (13). In addition, use of rhTRAIL combined with cisplatin enhanced apoptosis and growth inhibition in several ovarian cancer cell lines, which was related to cisplatininduced DR4 and DR5 cell surface expression (14).…”

mentioning

confidence: 99%

Enhanced Antitumor Efficacy of a DR5-Specific TRAIL Variant over Recombinant Human TRAIL in a Bioluminescent Ovarian Cancer Xenograft Model

Duiker¹,

Vries²,

Mahalingam

et al. 2009

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) is clinically evaluated as novel anticancer drug. rhTRAIL-DR5, a rhTRAIL variant that specifically binds to DR5 receptor, has recently been developed. We investigated whether rhTRAIL-DR5 is more efficient than rhTRAIL in combination with cisplatin in DR5-expressing human A2780 ovarian cancer cells. Design: Effect of cisplatin alone or in combination with rhTRAIL or rhTRAIL-DR5 on DR5 surface expression, apoptosis, and cell survival of A2780 was measured. Biodistribution analysis was done in mice with 125 I-rhTRAIL administered intravenously versus intraperitoneally. Antitumor efficacy of rhTRAIL-DR5 versus rhTRAIL was determined in an intraperitoneally growing bioluminescent A2780 xenograft model. Results: Cisplatin strongly enhanced DR5 surface expression. Both rhTRAIL and rhTRAIL-DR5 in combination with cisplatin induced high levels of caspase-3 activation, apoptosis, and cell kill, with rhTRAIL-DR5 being most potent. Intraperitoneal administration of 125 I-rhTRAIL resulted in a 1.7-fold higher area under the curve in serum, increased tumor exposure, and more caspase-3 activation in the tumor than intravenous administration. Intraperitoneal administration of rhTRAIL-DR5 delayed A2780 tumor progression, reflected in a mean light reduction of 68.3% (P = 0.015), whereas rhTRAIL or rhTRAIL-DR5 plus cisplatin resulted in 85% (P = 0.003) and 97% (P = 0.002) reduction compared with A2780 tumor progression in vehicle-treated animals. Combination of rhTRAIL-DR5 with cisplatin was more effective than cisplatin alone (P = 0.027). Conclusion: rhTRAIL-DR5 was superior over rhTRAIL in vitro and in vivo against DR5-expressing ovarian cancer also in combination with cisplatin. Intraperitoneal administration of rhTRAIL-DR5 warrants further exploration in ovarian cancer.

show abstract

“…Secretion of the pituitary hormone ACTH has been observed in a number of ovarian tumors and cell lines and has been implicated in the development of Cushing's syndrome among ovarian cancer patients in rare cases [26, 27]. The apoptotic mediators DR5, Fas, and FasL have each been previously investigated in ovarian cancer resulting in the observations that elevated DR5 expression correlates with decreased overall survival [28], and the macrophage infiltrate in ovarian cancer expresses high levels of Fas and FasL [29]. Although specific roles for IGFBP-1, TNFRI, and Kallikrein 10 remain to be characterized, these biomarkers have all been shown previously to be associated with the development and progression of ovarian cancer [30-32].…”

Section: Discussionmentioning

confidence: 99%

Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass

Nolen

Velikokhatnaya

Marrangoni

et al. 2010

Gynecologic Oncology

144

View full text Add to dashboard Cite

Objectives The diagnosis of an adnexal mass is a prevalent issue among women in the United States while current methods of identifying those at high risk of malignancy remain insufficient. Ineffective triage of women with malignant masses is associated with delayed or inappropriate treatment and a negative effect on disease outcome. Methods We performed an evaluation of 65 ovarian cancer-related biomarkers in the circulation of women diagnosed with an adnexal mass. Our subject group consisted of women diagnosed with benign masses and early and late stage ovarian cancer. Results Over half of the biomarkers tested were found to differ significantly between benign and malignant cases. As individual markers, HE4 and CA 125 provided the greatest level of discrimination between benign and malignant cases and the combination of these two biomarkers provided a higher level of discriminatory power than either marker considered alone. Multivariate statistical analysis identified several multi-marker panels that could discriminate early stage, late stage, and combined ovarian cancers from benign cases with similar or slightly improved SN/SP levels to the CA 125/HE4 combination, however these larger panels could not outperform the 2-biomarker panel in an independent validation set. We also identified a 3-biomarker panel with particular utility in premenopausal women. Conclusions Our findings serve to advance the development of blood-based screening methods for the discrimination of benign and malignant ovarian masses by confirming and expanding upon the superior utility of the CA 125/HE4 combination.

show abstract

An apoptotic molecular network identified by microarray: On the TRAIL to new insights in epithelial ovarian cancer

Cited by 18 publications

References 56 publications

c-FLIPL expression defines two ovarian cancer patient subsets and is a prognostic factor of adverse outcome

c-FLIPL expression defines two ovarian cancer patient subsets and is a prognostic factor of adverse outcome

Enhanced Antitumor Efficacy of a DR5-Specific TRAIL Variant over Recombinant Human TRAIL in a Bioluminescent Ovarian Cancer Xenograft Model

Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass

Contact Info

Product

Resources

About