Chemotherapy induces death receptor 5 in epithelial ovarian carcinoma

Arts, Hjg; Jong, de Steven; Hollema, Harmen; Hoor, KA Ten; Zee, van der Ate; Vries, de Elisabeth G. E.

doi:10.1016/j.ygyno.2003.11.054

Cited by 36 publications

(20 citation statements)

References 32 publications

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“…It was shown previously that in normal ovarian tissue, stromal TRAIL expression is completely missing but to some extent present in epithelial cells (22). This suggests, that the stromal expression detected by us is most likely a reaction of the microenvironment to the tumor cells.…”

Section: Discussionsupporting

confidence: 57%

Perturbation of the Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Cascade in Ovarian Cancer: Overexpression of FLIPL and Deregulation of the Functional Receptors DR4 and DR5

Horak¹,

Pils²,

Kaider³

et al. 2005

Clinical Cancer Research

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Purpose: Epithelial ovarian cancer is the most common cause of mortality from gynecologic malignancies. Due to advanced stage at diagnosis, most patients need systemic treatment in addition to surgery. Tumor necrosis factor (TNF)^related apoptosis-inducing ligand (TRAIL) is a member of the TNF family with a promising toxicity profile and synergistic activity with chemotherapeutic agents. Experimental Design: We used an arrayed panel of epithelial ovarian cancer tissue to assess the protein expression of TRAIL and the clinically most relevant members of its pathway death receptors 4 and 5 (DR4 and DR5) and the long form of FLICE inhibitory protein (FLIP L ). Results: We could show that a majority (66.2%) of the tumor tissues displayed either reduced DR4/DR5 expression (20.6%), increased FLIP L expression (39.7%), or both (5.9%) as determined by immunohistochemistry. Furthermore, higher TRAIL expression in the surrounding connective tissue but not in the tumor cells is significantly (P < 0.05) linked with favorable overall survival in advanced-stage patients. Conclusions: Mechanisms to escape the immune surveillance mediated byTRAIL are developed by ovarian cancer cells in a high percentage. TRAIL expression in the ovarian cancer microenvironment has an effect on overall survival. These findings enhance our understanding of ovarian cancer pathology and might be helpful in guidingTRAIL-based therapy in future.Despite great clinical and research efforts, the etiology of ovarian cancer remains poorly understood. A majority (90%) of these tumors stem from ovarian surface epithelium, which is similar to the mesothelial lining of other abdominal organs. Beyond family history, the most important risk factors for ovarian cancer include early menarche, late menopause, nulliparity, and in contrast, the use of anovulatory drugs that reduces the risk. The epidemiologic observation that all factors that limit the number of ovulations over lifetime are protective against ovarian cancer resulted in the so-called incessant ovulation theory decades ago (1).Over the past several years, the molecular mechanisms behind the genetic predisposition for ovarian cancer have been elucidated. Germ line mutations in BRCA1 and BRCA2, the genes responsible for hereditary breast and ovarian cancer and in hMLH1 and hMSH2, responsible for hereditary nonpolyposis colon cancer, are also the basis for a majority of cases of familial ovarian cancer. Originally identified by positional cloning, all these genes were later shown to be involved in the maintenance of genome integrity, implying that DNA repair mechanisms are under considerable challenge in ovarian tissue. Induction of apoptosis plays a pivotal role in cellular homeostasis, and in this scenario, the impairment of any of its components may result in accumulation of genetic defects, preceding cancer development (2).Apoptosis is induced either by binding of ligands to specific death receptors on cell surface or by unspecific cellular stress, which promotes cytochrome c release from mi...

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Section: Discussionsupporting

confidence: 57%

Perturbation of the Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Cascade in Ovarian Cancer: Overexpression of FLIPL and Deregulation of the Functional Receptors DR4 and DR5

Horak¹,

Pils²,

Kaider³

et al. 2005

Clinical Cancer Research

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“…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). This might imply that combinatory strategies with DR5 targeted agents are more effective than combinational regimes with DR4 targeted drugs in ovarian cancer.…”

Section: Discussionmentioning

confidence: 89%

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

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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.

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“…These results are consistent with those in the literature showing either Trail overexpression in early-stage EOC compared with advanced-stage EOC, or no association with disease stage. 21,22 However, at the RNA level, TRAIL was overexpressed in poorly differentiated (grade 2 and 3) tumors compared with welldifferentiated (grade 1) tumors. 23 This discordance between protein levels and RNA levels was reported previously in breast cancer 24 ; it also was reflected in our microarray analysis, in which grade 3 TOV tumors expressed higher levels of TRAIL than LMP tumors, and in another published microarray study in which TOV tumors were compared with normal ovarian surface epithelium cells.…”

Section: Discussionmentioning

confidence: 98%

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

Ouellet

Page

Madore

et al. 2007

Cancer

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Protein‐imprinted soft‐gel composite microspheres with magnetic susceptibility (MS‐PIGMs) were prepared by inverse suspension polymerization using Fe3O4 particles as magnetically susceptible component and bovine serum albumin and lysozyme (Lyz) as templates, respectively. The average content of magnetically susceptible component (Fe3O4) inside MS‐PIGMs was determined using thermogravimetric analyzer, and the magnetic characteristics of MS‐PIGMs were measured by vibrating sample magnetometer. The results showed that the resulting MS‐PIGMs had a certain magnetic response to external magnetic fields, and their average content of Fe3O4 was 2.08%. Their recognition specificity was investigated using BSA and Lyz as both templates and control molecules and characterized by high‐performance liquid chromatography, and the mechanism of imprinting and recognition was analyzed. It was shown that the resulting BSA imprinted soft‐gel composite microspheres with magnetic susceptibility (BSA‐PIGMs) and Lyz imprinted soft‐gel composite microspheres with magnetic susceptibility (Lyz‐PIGMs). All exhibited good recognition selectivity for their templates, and the relative separation factor (β) was 4.75 and 5.88, respectively. The recognition selectivity of MS‐PIGMs to their templates depended mainly on the synergic action of a large quantity of hydrogen binding being caused by complementation and very close contact of outer surface of proteins with inner surface of “imprinting cavities.” © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006

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Chemotherapy induces death receptor 5 in epithelial ovarian carcinoma

Cited by 36 publications

References 32 publications

Perturbation of the Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Cascade in Ovarian Cancer: Overexpression of FLIPL and Deregulation of the Functional Receptors DR4 and DR5

Perturbation of the Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Cascade in Ovarian Cancer: Overexpression of FLIPL and Deregulation of the Functional Receptors DR4 and DR5

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

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

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