The detection, treatment, and biology of epithelial ovarian cancer

Gubbels, Jennifer A. A.; Claussen, Nick; Kapur, Arvinder; Patankar, Manish S.

doi:10.1186/1757-2215-3-8

Cited by 66 publications

(62 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Ovarian cancer is the number one killer of all gynecologic malignancies (34). Current therapeutic approaches have a high failure rate, leading to a low 5-year survival rate of 25% to 35% (35).…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy Dosing Schedule Influences Drug Resistance Development in Ovarian Cancer

Souza

Zahedi

Badame

et al. 2011

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Drug resistance leads to chemotherapy failure and is responsible for the death of a great majority of patients with metastatic, late-stage ovarian cancer. The present study addressed whether changes in the chemotherapy dosing schedule affect the development, further worsening, or circumvention of drug resistance in chemosensitive and chemoresistant ovarian cancer. Severe combined immunodeficient mice bearing HeyA8 and HeyA8-MDR xenografts were treated with docetaxel intermittently (1Â/wk or 3Â/wk) or continuously for 21 days. Tumor mRNA expression of genes implicated in docetaxel resistance was measured by quantitative real-time-PCR. Analyzed genes included those encoding for the drug efflux transporters mdr1 and mrp7 and for molecules that interfere with or overcome the effects of docetaxel, including b-tubulinIII, actinin4, stathmin1, bcl2, rpn2, thoredoxin, and akt2. In both models, continuous docetaxel resulted in greater antitumor efficacy than 1Â/wk or 3Â/wk dosing and did not induce upregulation of any analyzed genes. Once weekly dosing caused upregulation of various drug resistance-related genes, especially in chemoresistant xenografts. More frequent, 3Â/wk dosing diminished this effect, although levels of various genes were higher than for continuous chemotherapy. Drug efflux transporter expression was further examined by Western blotting, confirming that intermittent, but not continuous, docetaxel induced significant upregulation. Overall, our results show that the presence and length of treatment-free intervals contribute to the development of drug resistance. Elimination of these intervals by continuous dosing resulted in superior antitumor efficacy and prevented drug resistance induction in chemosensitive and chemoresistant disease. These results encourage the clinical implementation of continuous chemotherapy to overcome and/or prevent drug resistance in newly diagnosed and recurrent, refractory ovarian cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Chemotherapy Dosing Schedule Influences Drug Resistance Development in Ovarian Cancer

Souza

Zahedi

Badame

et al. 2011

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…The latest cancer statistics in China reported the incidence rate of ovarian cancer to be 7.95 cases per 100,000 individuals, and the yearly increase in incidence was higher in urban regions compared with rural regions (4,5). As the ovaries are anatomically located deep within the pelvis, the majority of patients with early-stage ovarian cancer exhibit few specific clinical symptoms, and ovarian cancer continues to lack sensitive and specific biomarkers for early diagnosis in the clinic (6). As a result, the early detection of ovarian cancer is challenging.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of S100A14 in human serous ovarian carcinoma

et al. 2015

View full text Add to dashboard Cite

Abstract. S100 calcium binding protein A14 (S100A14) is a member of the S100 protein family that plays an important role in the progression of several types of cancer. In the present study, the expression and clinical effect of S100A14 was evaluated in serous ovarian carcinoma (SOC). SOC tissue specimens and a panel of normal ovarian and fallopian tubal tissue specimens were obtained between November 2008 and August 2012 from the Affiliated Hospital of Qingdao University. Immunohistochemistry (IHC) was used to detect the expression of S100A14 in the SOC and normal control tissues. In addition, ELISA was performed to assess S100A14 expression in a subset of serum samples. The association between the expression of S100A14 in SOC and the corresponding clinical and pathological data was analyzed. The IHC results revealed that S100A14 was mainly located in the cytoplasm of the majority of SOC cells, and the expression levels of S100A14 in the tumor tissues were significantly increased compared with the levels identified in normal ovarian specimens (P<0.001). Consistently, the serum levels of S100A14 in patients with SOC were also increased compared with the levels in healthy individuals (P<0.001). S100A14 expression was similar in the epithelium of SOC lesions and the fallopian tube, which supported the dualistic model for ovarian serous carcinogenesis. Additional analysis of the expression of S100A14 and corresponding clinical and pathological data revealed the correlation between the elevated expression of S100A14 and resistance to platinum-based chemotherapy. However, the protein level of S100A14 was not associated with the pathological stage, differentiation or metastasis of SOC. Overall, the present results demonstrate that S100A14 is likely to be involved in the resistance of SOC to platinum-based chemotherapy.

show abstract

“…Ovarian cancer is the most lethal gynecological cancer in women because early detection is extremely difficult (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and because it is resistant to most chemotherapic drugs (15)(16)(17). The average lifespan after detection is 40.8 months for serous cancer, 21.3 months for clear cell carcinomas, 17.6 months for mucinous carcinomas and 50.9 months for endometrioid ovarian carcinomas (11).…”

Section: Introductionmentioning

confidence: 99%

Epiregulin as a marker for the initial steps of ovarian cancer development

Amsterdam

Shezen²,

Raanan³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. Epiregulin (Ep) was found to be produced in noncancer ovarian cells in response to gonadotropin stimulation as well in ovarian cancer cells in an autonomous manner. However, there were no systematic follow-up studies of Ep expression in the development of different stages of ovarian cancer. Using specific antibodies to Ep and the indirect immunocytochemistry methods, we found that in normal ovary the staining for Ep was mainly confined to the epithelial cells, while the stromal cells were only occasionally and moderately stained. In contrast in benign serous and mucinous tumors most of the tumor cells showed a clear staining in the cytoplasm. In borderline serous and mucinous tumors the staining was much more intensive, and appear occasionally in aggregated form. In serous, mucinous and endometrioid carcinomas labeling remain high, with more frequent aggregated form. It is suggested that follow-up of the expression of Ep can serve as a reliable early indication of the development of ovarian cancer. Moreover, the cytoplasmic aggregation of Ep may suggest a specific mechanism of the release of this growth factor to the extracellular space in order to exert its autocrine and paracrine effect on the family of the EGF receptors.

show abstract

The detection, treatment, and biology of epithelial ovarian cancer

Cited by 66 publications

References 113 publications

Chemotherapy Dosing Schedule Influences Drug Resistance Development in Ovarian Cancer

Chemotherapy Dosing Schedule Influences Drug Resistance Development in Ovarian Cancer

Overexpression of S100A14 in human serous ovarian carcinoma

Epiregulin as a marker for the initial steps of ovarian cancer development

Contact Info

Product

Resources

About