Elevated cyclooxygenase-2 expression correlates with diminished survival in carcinoma of the cervix treated with radiotherapy

Gaffney, David K.; Holden, Joseph A.; Davis, M.; Zempolich, Karen; Murphy, Kelley J.; Dodson, Mark K.

doi:10.1016/s0360-3016(00)01583-2

Cited by 140 publications

(80 citation statements)

References 8 publications

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“…These data are in line with one published study on human rectal cancer pretreated with chemoradiotherapy [45] but are not in accordance with the results reported in studies on squamous cell carcinoma of head and neck and cervix treated with radiotherapy alone or radiochemotherapy [39,27,9,18].…”

Section: Discussionsupporting

confidence: 63%

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The role of COX-2 in rectal cancer treated with preoperative radiotherapy

et al. 2008

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Radiotherapy is one of the principal modalities of rectal cancer treatment, and the ability to predict radio resistance could potentially improve survival through a targeted treatment approach. Cyclooxygenase-2 (COX-2) may protect against damage by irradiation that would justify the use of COX-2 inhibitors. The purpose of this study was to investigate the potential role of COX-2 in tumor response and outcome of patients with rectal cancer treated preoperatively with radiotherapy. Using immunohistochemistry, we examined COX-2 expression in 88 surgical specimens of rectal cancer treated preoperatively and in 26 pretherapeutic biopsies. We tested whether COX-2 expression was correlated with clinico-pathologic parameters and with survival and local recurrence. COX-2 was expressed in 50% of the pretherapeutic tumor biopsies and in 88.6% of post-irradiated surgical samples. COX-2 expression was correlated only with enhanced tumor inflammation (p=0.03) and with tumor volume exceeding 30 cc (p=0.05). COX-2 was not significantly correlated with patient survival, but none of the patients with COX-2 negative tumors did recur locally, whereas 80% of patients with local recurrences have COX-2 positive tumors. We conclude that COX-2 expression is overexpressed in the majority of rectal cancers treated with radiotherapy and likely plays a role in local relapse.

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Section: Discussionsupporting

confidence: 63%

“…In oral squamous cell carcinoma [39] and in laryngeal cancer [27] elevated COX-2 expression has been associated with radio resistance and diminished survival. Expression of COX-2 was also correlated with poor prognosis in squamous cell carcinoma of the uterine cervix treated with radiation therapy [9,18].…”

Section: Discussionmentioning

confidence: 92%

The role of COX-2 in rectal cancer treated with preoperative radiotherapy

et al. 2008

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“…For this enzyme the link to carcinogenesis, tumor progression and metastatic tumor spread has been firmly established. Overexpression of COX-2 in human tumors is associated with a poor prognosis and a poor response to radiation therapy [15][16][17][18]. Pharmacological inhibitors of COX-2 have shown to enhance the radiation response of tumors of several histotypes in vitro and in vivo without serious side effects on normal tissues [19,20].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of invasion-associated thromboxane synthase sensitizes experimental gliomas to γ-radiation

et al. 2008

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The invasion-and apoptosis-associated thromboxane synthase gene encoding an enzyme of the arachidonic acid pathway has been implicated in glioma progression. Furegrelate, a specific inhibitor of thromboxane synthase, blocks cell motility, induces apoptosis and increases sensitivity to drug induced apoptosis in human glioma cells in vitro. The impact of furegrelate on the sensitivity of human glioma cells to c-irradiation was analyzed using colony formation assay in vitro and an orthotopic mouse model in vivo. Pre-treatment of glioma cells with furegrelate increases radiation sensitivity of cultured glioma cells. Treatment of experimental gliomas with suboptimal doses of radiation and furegrelate results in a significant decrease in tumor volumes compared to untreated controls. Thus, the specific thromboxane synthase inhibitor furegrelate increases death response induced by c-radiation in glioma cells in vitro and sensitizes experimental gliomas to radiation treatment in vivo.

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“…[19][20][21] Several reports have shown that COX-2 is associated with adverse outcome after treatment of cervical cancer. 11,12,18,22 Gaffney et al 11 reported that increased expression of COX-2 was associated with decreased overall survival (p=0.021) and disease free survival (p=0.015). Kim et al 12 also showed a decreased overall survival (p= 0.003) and disease free survival in their COX-2 positive group.…”

Section: Discussionmentioning

confidence: 99%

“…9,10 Recently, several studies have reported that specific biological markers, such as cyclooxygenase (COX)-2, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are significantly correlated with tumor control, survival after RT with or without chemotherapy. [11][12][13][14][15][16][17][18] The goals of this prospective study were 1) to determine the factors associated with the tumor volume response to RT with or without chemotherapy and 2) to determine the relationship between the tumor volume response and alteration of the expression of the biological markers during RT with or without chemotherapy. …”

Section: Introductionmentioning

confidence: 99%

Correlation between tumor volume response to radiotherapy and expression of biological markers in patients with cervical squamous cell carcinoma

et al. 2009

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Objective: To determine the factors associated with tumor volume response to radiotherapy (RT) in cervical cancer patients, and the relationship between the tumor volume response and alteration of the expression of biological markers during RT. Methods: Twenty consecutive patients with cervical squamous cell carcinoma who received definitive RT were enrolled. Tumor volumes were calculated by MRI examinations performed at the start of RT (pre-RT), at the fourth week of RT (mid-RT), and 1 month after RT completion (post-RT). Two serial punch biopsies were performed at preand mid-RT, and immunohistochemical staining was performed for cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR). Results: For the pre-RT evaluation, fourteen (70%) and eleven (55%) patients showed positive immunoreactivity for COX-2 and EGFR, respectively. Among the seven patients whose median percentage residual tumor at mid-RT (V2R) was greater than 0.5, seven (100%, p=0.0515) and five (71.4%, p=0.3742) patients showed positive immunoreactivity for COX-2 and EGFR, respectively. The logistic regression analysis showed that positive immunoreactivity for both COX-2 and EGFR at pre-RT were associated with V2R (p=0.0782). For the mid-RT evaluation, eight cases showed an interval increase in the distribution of immunoreactivity for COX-2, and six out of the eight patients had a V2R greater than 0.5 (p=0.2222). Conclusion:The poor mid-RT tumor response was associated with the coexpression of COX-2 and EGFR.

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Elevated cyclooxygenase-2 expression correlates with diminished survival in carcinoma of the cervix treated with radiotherapy

Cited by 140 publications

References 8 publications

The role of COX-2 in rectal cancer treated with preoperative radiotherapy

The role of COX-2 in rectal cancer treated with preoperative radiotherapy

Inhibition of invasion-associated thromboxane synthase sensitizes experimental gliomas to γ-radiation

Correlation between tumor volume response to radiotherapy and expression of biological markers in patients with cervical squamous cell carcinoma

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