Progress in Gynecologic Cancer Research: The Gynecologic Oncology Group Experience

Omura, George

doi:10.1053/j.seminoncol.2008.07.007

Cited by 20 publications

(8 citation statements)

References 123 publications

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“…It is a component of first-line treatment for testicular, ovarian, cervical, endometrial, bladder, head and neck, lung, and gastroesophageal cancers (Hussain et al, 2008; Omura et al, 2008; Gallagher et al, 2008; Yang et al, 2008; Lustberg and Edelman, 2007; Fischer and Arcaro, 2008; Cen and Ajani, 2007). It is also used as a second or third-line treatment for prostate and pancreatic cancers, metastatic cancer of the breast, and for melanoma and gliomas (Carrick et al, 2004; Oh et al, 2007; Saif and Kim, 2007; Atallah and Flaherty, 2005; Glioma Meta-Analysis Trialists Group, 2002).…”

Section: Introductionmentioning

confidence: 99%

Enhancing Tumor-Specific Uptake of the Anticancer Drug Cisplatin with a Copper Chelator

et al. 2010

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SUMMARY Uptake of the anticancer drug cisplatin is mediated by the copper transporter Ctr1 in cultured cells. Here we show in human ovarian tumors that low levels of Ctr1 mRNA are associated with poor clinical response to platinum-based therapy. Using a mouse model of human cervical cancer, we demonstrate that combined treatment with a copper chelator and cisplatin increases cisplatin-DNA adduct levels in cancerous but not in normal tissues, impairs angiogenesis, and improves therapeutic efficacy. The copper chelator also enhances the killing of cultured human cervical and ovarian cancer cells with cisplatin. Our results identify the copper transporter as a therapeutic target, which can be manipulated with copper chelating drugs to selectively enhance the benefits of platinum-containing chemotherapeutic agents.

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Section: Introductionmentioning

confidence: 99%

Enhancing Tumor-Specific Uptake of the Anticancer Drug Cisplatin with a Copper Chelator

et al. 2010

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“…Since that report many clinicians have also incorporated the use of chemoradiation for the treatment of vaginal cancers. The use of chemoradiation reached wide-spread applicability in the late 1990s(10). …”

Section: Introductionmentioning

confidence: 99%

Factors Affecting Risk of Mortality in Women With Vaginal Cancer

Shah

Goff

Lowe

et al. 2009

Obstetrics &Amp; Gynecology

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Objective-To estimate the current effect of demographics, pathology, and treatment on mortality among women with vaginal cancer.Methods-Using data from 17 population-based cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) program, 2,149 women diagnosed with primary vaginal cancer between 1990 to 2004 were identified. The association between various demographic factors, tumor characteristics, and treatments and risk of vaginal cancer mortality were evaluated using Cox proportional hazards modeling.Results-The mean age at diagnosis was 65.7 ± 14.3 years. Approximately 66% of all cases were non-Hispanic whites. Incidence was highest among African-American women (1.24/100,000 personyears). The 5-year disease specific-survival was 84% (Stage I), 75% (Stage II), and 57% (Stage III/ IV). In a multivariate adjusted model, women with tumors greater than 4 cm and advanced disease had elevated risks of mortality (HR 1.71, 4.67, respectively). Compared to women with squamous cell carcinomas, patients with vaginal melanoma had a 1.51-fold (95% CI: 1.07-2.41) increased risk of mortality. Surgery alone as a treatment modality had the lowest risk of mortality. The risk of mortality has decreased over time, as women diagnosed after 2000 had an adjusted 17% decrease in their risk of death compared to women from 1990-1994.Conclusion-Stage, tumor size, histology, and treatment modality significantly affect a woman's risk of mortality from vaginal cancer. There appears to be a survival advantage that is temporally related with the advent of chemoradiation.

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“…Carboplatin is equally efficient but less toxic and easier to administer than cisplatin, thus, it replaced cisplatin as the standard treatment for ovarian cancer (Ozols et al 2003, Omura 2008. Paclitaxel is an antimitotic drug, which alters the dynamics of the cellular microtubules, which maintain cellular structure and are essential for diverse cellular functions such as cell cycle, cell signaling, and intracellular trafficking (Seve & Dumontet 2008).…”

Section: Introductionmentioning

confidence: 99%

“…First-line treatment for advanced ovarian cancer consists of a combination of paclitaxel and carboplatin (Ozols et al 2003, Omura 2008. Carboplatin is equally efficient but less toxic and easier to administer than cisplatin, thus, it replaced cisplatin as the standard treatment for ovarian cancer (Ozols et al 2003, Omura 2008.…”

Section: Introductionmentioning

confidence: 99%

The miR-200 family controls -tubulin III expression and is associated with paclitaxel-based treatment response and progression-free survival in ovarian cancer patients

Leskelä¹,

Leandro‐García²,

Mendiola³

et al. 2010

Endocrine Related Cancer

186

145

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Ovarian cancer remains one of the leading causes of cancer deaths. Thus, new biomarkers predictive of response to the standard paclitaxel-carboplatin treatment are needed to improve chemotherapy strategies. MicroRNAs have the potential to modify drug outcomes. Based on this, we have demonstrated in this study that patients with a high expression of the miR-200 family show low levels of b-tubulin class III in ovarian carcinoma. In addition, we have established the clinical relevance of these microRNAs for ovarian cancer patients' treatment response and survival. In a well-characterized series of 72 ovarian carcinomas, the expressions of miR-141, miR-200a, miR-200b, miR-200c, and miR-429 were quantified by quantitative reverse transcription-PCR, and the protein content of b-tubulin isotypes I, II, and III was determined by immunohistochemistry. The relationship between these microRNAs, b-tubulin expression, response to paclitaxel-based treatment, progression-free survival (PFS) and overall survival was determined. While isotype I had constant high levels, protein expression of b-tubulins II and III was mutually exclusive. Low tumoral miR-200 expression was significantly associated with high b-tubulin III protein content (P values range, 0.047-!0.0001), and patients without complete response (CR) had lower miR-200c levels than patients with CR (hazard ratio (HR)Z1.43, 95% confidence interval (CI)Z1.02-1.99, PZ0.037, multivariate analysis). Additionally, low miR-200 family expression had a trend toward poor PFS (HRO2.0, P values 0.051, 0.054, and 0.079 for miR-200c, miR-141, and miR-429 respectively, multivariate analysis). In conclusion, miR-200 family members affect the final b-tubulin III protein content of ovarian carcinomas. Furthermore, these microRNAs might constitute the biomarkers of response to paclitaxel-based treatments and relapse/progression of advanced stage ovarian carcinoma patients.

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Progress in Gynecologic Cancer Research: The Gynecologic Oncology Group Experience

Cited by 20 publications

References 123 publications

Enhancing Tumor-Specific Uptake of the Anticancer Drug Cisplatin with a Copper Chelator

Enhancing Tumor-Specific Uptake of the Anticancer Drug Cisplatin with a Copper Chelator

Factors Affecting Risk of Mortality in Women With Vaginal Cancer

The miR-200 family controls -tubulin III expression and is associated with paclitaxel-based treatment response and progression-free survival in ovarian cancer patients

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