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Although radiation therapy was known to be effective to cervical cancer, loco-regional recurrences are frequently found in patients. We aimed to identify a molecular marker predicting the response of cervical cancer to radiotherapy. We included the patients (n = 149) with cervical cancer who had undergone radiotherapy from 2004 to 2006. Tumor samples were collected to examine the association between the expression of S-phase kinase-associated protein 2 (SKP2) and prognosis in cervical cancer. We found higher expression of SKP2 associated with recurrence (HRs: 2.52, p < 0.001), death (HRs: 2.01, p < 0.001) and higher locoregional recurrence rate (HRs: 3.76, p < 0.001). Cervical cancer cell lines with higher expression of SKP2 showed higher colony formation, cell survival rate and fewer DNA damages after irradiation. SKP2-C25, an inhibitor for SKP2 activity, dose-dependently decreased cell viability after irradiation and knockdown of SKP2 impaired DNA-damage response and sensitized the cervical cancer cells to irradiation. Our data showed the SKP2 represents a promising tool to identify patients with cervical cancer who have a higher risk of locoregional recurrence after radiotherapy. Targeting SKP2 may serve as a potential radiosensitizer for developing effective therapeutic strategies against cervical cancer.

Objective Epithelial ovarian cancer is the most lethal gynecologic cancer worldwide and chemoresistance is one of the major causes of treatment failure. We investigated whether ERCC1 , TAU , TOPO2A , TOPO1 , P53 , and C-MYC expression could be used as predictors for treatment outcomes. Materials and methods Immunohistochemical staining was used to examine the expression of these biomarkers in resected tumor specimens from 38 patients treated in our institute. Clinicopathological data including demographics, staging, histological type, treatment response, expression of the biomarkers, and patient outcomes were analyzed. Results The median follow-up period was 47.5 months (range, 10–135 months) and the median overall survival was 56.0 months. Patients who did not have expression of ERCC1 , and those who had expression of TOPO1 had significantly better overall survival. Cox regression analysis also confirmed that these two biomarkers were significant independent factors predicting survival ( ERCC1 , hazard ratio 5.51, 95% confidence interval: 2.02–14.00, p = 0.001; TOPO1 , hazard ratio 0.22, 95% confidence interval: 0.06–0.77, p = 0.017). Conclusion We concluded that poor overall survival was significantly associated with positive ERCC1 and negative TOPO1 expression. The results might be the consequence of chemoresistance to platinum and camptothecins, both of which are commonly used regimens in the treatment of epithelial ovarian cancer.

Objective We attempted to investigate the safety and efficacy of alternative weekly topotecan dosing in a heavily pretreated Taiwanese population with recurrent epithelial ovarian cancer (EOC) and primary peritoneal carcinoma (PPC). Materials and methods We retrospectively reviewed the medical records of patients with recurrent EOC and PPC who had been treated with weekly topotecan between November 2008 and May 2012. Topotecan was given at a dose of 2.75–4 mg/m 2 via a 30-minute intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity occurred. Results Thirty-two patients were identified and 24 (75%) of them had received at least two previous regimens of chemotherapy; the median number of treatment courses was seven. The main toxicities (Grades 3 and 4) were anemia in seven (21.9%), neutropenia in six (18.8%), and thrombocytopenia in two patients (6.2%). No deaths were attributable to the therapy. Overall, seven patients (21.9%) showed a partial response (PR), while seven patients (21.9%) with stable disease (SD) were observed. Furthermore, we found a favorable response and toxicity profile in patients who received the lowest dose intensity (2.75 mg/m 2 ). The median progression-free survival (PFS) and overall survival (OS) were 3 months [95% confidence interval (CI) 2.7–3.2] and 20 months (95% CI 11.1–28.9), respectively. Conclusion Topotecan administered as a weekly dosage (2.75–4 mg/m 2 ) seems to be a tolerable regimen with modest activity in a Taiwanese population. Although the lower dose schedule showed a higher response with a better toxicity profile, further studies with more cases are needed to confirm this finding.

Previous studies have suggested that cancer stem cells (CSCs) resisted radiotherapy and chemotherapy. P16INK4A is a biomarker for cervical carcinogenesis and reduces proliferation of stem cells. We aimed to investigate the expression and clinical significance of cyclin-dependent kinase inhibitor 2A (P16INK4A), sex determining region Y-box 2 (SOX2), and Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1) in cervical cancer treated with radiotherapy and cervical cell line models. The expressions of P16INK4A, SOX2, and ALDH1A1 were performed by immunohistochemical staining of tumor samples from 139 cervical cancer patients with International Federation of Gynecology and Obstetrics stages Ib to IV. The staining showed high expression in 100, 107, and 13 patients with P16INK4A (&gt, 80%), SOX2 (&ge, 10%), and ALDH1A1 (50%), respectively. The high-P16INK4A group had a higher five-year overall survival (OS) rate and disease-free survival (DFS) than the low-P16INK4A group (OS: 62.0% and 35.2%, p = 0.016, DFS: 60.0% and 31.2%, p = 0.002). The low-P16INK4A/high-SOX2 and low-P16INK4A/high-ALDH1A1 groups had a worse five-year OS and DFS rate than the high-P16INK4A/low-SOX2 and high-P16INK4A/low-ALDH1A1 groups, respectively. Depletion of P16INK4A promoted chemoresistance and radioresistance of cervical cancer cells increased the expression of SOX2 and ALDH1A1 and exhibited higher self-renewal ability. These results suggest that lower P16INK4A expression associated with higher CSC markers predicts poor prognostic outcomes and is a promising target in patients with cervical cancer.

Pogostemon cablin (PC) is a traditional herbal medicine used in the treatment of the common cold, nausea, diarrhea, and even for headaches and fever. However, the mechanisms underlying the anti-proliferative activity of PC in endometrial cancer (EC) cells have yet to be fully elucidated. This study investigated the anticancer effects of an aqueous extract of Pogostemon cablin (PCAE), specifically induced apoptosis in EC (Ishikawa) cells. Proliferation of EC cells following exposure to PCAE was assessed by an MTT assay. DNA content and the induction of cell cycle apoptosis were analyzed by flow cytometry (FACS Calibur). Protein caspase-3 and, -9 as well as AIF were investigated using Western blot. Our results demonstrate growth inhibition of Ishikawa cells by PCAE. Furthermore, caspase-3 activity caused PCAE-treated cell lines to accumulate in apoptosis. Gene expression profiling (GEP) results further suggest that, in addition to its known effects with regard to EC prevention, PCAE may also exert antitumor activity on established EC cells. Many previous studies have identified the chemo-preventive effects of natural plant materials and the potential role of these materials in chemotherapy. This current study used human EC Ishikawa cells to investigate the anti-tumor effects of PCAE in EC cells. Our results demonstrate that PCAE inhibits the growth of cancer cells and induces apoptosis, which suggests the potential applicability of PCAE as an antitumor agent.

Although radiation therapy was known to be effective to cervical cancer, loco-regional recurrences are frequently found in patients. We aimed to identify a molecular marker predicting the response of cervical cancer to radiotherapy. We included the patients (n = 149) with cervical cancer who had undergone radiotherapy from 2004 to 2006. Tumor samples were collected to examine the association between the expression of S-phase kinase-associated protein 2 (SKP2) and prognosis in cervical cancer. We found higher expression of SKP2 associated with recurrence (HRs: 2.52, p0.001), death (HRs: 2.01, p0.001) and higher locoregional recurrence rate (HRs: 3.76, p0.001). Cervical cancer cell lines with higher expression of SKP2 showed higher colony formation, cell survival rate and fewer DNA damages after irradiation. SKP2-C25, an inhibitor for SKP2 activity, dose-dependently decreased cell viability after irradiation and knockdown of SKP2 impaired DNA-damage response and sensitized the cervical cancer cells to irradiation. Our data showed the SKP2 represents a promising tool to identify patients with cervical cancer who have a higher risk of locoregional recurrence after radiotherapy. Targeting SKP2 may serve as a potential radiosensitizer for developing effective therapeutic strategies against cervical cancer.

The purpose of the study was to analyze negative versus positive immunoexpression of epithelial cadherin (E-cadherin) and p53 in patients with primary advanced ovarian clear cell adenocarcinoma (OCCA) and its significance in relation to clinical features, progression-free survival and overall survival (OS).Protein expression of E-cadherin and p53 was immunohistochemically evaluated in 61 OCCA patients with stages IIC to IV. The clinical factors studied included stage, age, CA-125, residual tumors, and chemotherapy regimens.Positive p53 immunoexpression was 44.8% (26/58) of OCCAs; in contrast, E-cadherin immunoexpression was observed in 75.9% (44/58) of OCCAs. The expected 5-year OS rate of OCCA treated with paclitaxel-based chemotherapy was significantly better than non-paclitaxel-based chemotherapy (40% vs 0%, P = 0.001). The expected 5-year OS rate of OCCA patients with positive E-cadherin immunoexpression (10%) was also significantly better than patients with negative E-cadherin immunoexpression (≤10%) (35% vs 0%, P = 0.02). The expected 5-year OS rate of those receiving paclitaxel-platinum chemotherapy was not significantly different from platinum-based chemotherapy for those with negative E-cadherin immunoexpression (P = 0.11). The expected 5-year OS rate of those receiving paclitaxel-based chemotherapy was better than non-paclitaxel-based chemotherapy for those with positive E-cadherin immunoexpression (43% vs 0%, P = 0.01). Paclitaxel-based chemotherapy and positive E-cadherin immunoexpression were 2 independent prognostic factors in OS of patients with OCCA (P = 0.01 and 0.04, respectively).E-cadherin is a useful prognostic marker for OCCA patients, and paclitaxel-based chemotherapy can improve survival among patients with positive E-cadherin immunoreactivity.

Objective . The aim was to compare survival in pure and mixed-type advanced clear cell ovarian carcinoma and to determine the benefits among patients with pure advanced clear cell ovarian carcinoma treated in paclitaxel-platinum-based chemotherapy in comparison with those treated in conventional platinum-based chemotherapy after primary surgery. Methods . Between 1994 and 2001, 31 women with stage III and IV pure clear cell ovarian carcinoma and nine patients with stage III and IV mixed-type clear cell carcinoma were identified from the tumor registry of six institutions. All patients underwent cytoreductive surgery followed by conventional platinum-based chemotherapy or paclitaxel and platinum-based chemotherapy. Results . The median survival of women with pure clear cell carcinoma was 11 months, compared to 48+ months for those with mixed-type clear cell carcinoma ( P = 0.003). Overall, for women with pure clear cell carcinoma, 35% had clinically complete responses to chemotherapy. For women with pure clear cell carcinoma treated with paclitaxel-platinum-based chemotherapy, the median survival was significantly longer than for those treated with conventional platinum-based chemotherapy (16.26 vs. 10.75 months, P = 0.045; with optimal cytoreduction, 40.95 vs. 9.02 months, P = 0.028). Univariate analysis showed paclitaxel-platinum-based treatment was the only favorable prognostic factor for women with advanced pure clear cell ovarian carcinoma ( P = 0.05). Conclusions . Patients with advanced pure clear cell ovarian carcinoma have poorer prognoses than those with the mixed type. Paclitaxel-platinum-based chemotherapy improved survival among our patients with advanced pure clear cell carcinoma, especially for those with optimal cytoreduction.

Objective. The purpose of the study was to identify the relationship between preoperative serum levels of carcinoembryonic antigen (CEA) and clinicopathological variables in early-stage adenocarcinoma of the uterine cervix. Methods. From February 1990 to August 2002, 117 patients with surgically treated early-stage cervical adenocarcinoma that had had preoperative serum CEA evaluations were retrospectively reviewed. The cut-off value for CEA, based on the manufacturer's recommendations, was 5 ng/ml. For an evaluation of the relationship between the clinicopathological factors and increased levels of serum tumor markers, the Chi-Square/Fisher's exact test and logistic regression were used for univariate and multivariate analysis, respectively. Results. The mean age of the patients was 46 years (range, 21–78). Of the 117 patients, 28 had preoperative serum CEA levels greater than 5 ng/ml. In a univariate analysis, the increased marker was associated with a larger tumor size, presence of lymphovascular invasion, and deeper cervical wall invasion. However, in a multivariate analysis, the preoperative CEA level had a significant impact on the determination of the depth of stromal invasion (OR 4.12, 95% CI 1.97–8.68, P Conclusion. In early-stage cervical adenocarcinoma, preoperative serum CEA levels seem to be useful in estimating the depth of cervical stromal invasion. Assessment of tumor antigen CEA levels should be integrated with the routine examination in the work-up of patients with adenocarcinoma of the uterine cervix.