• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7669-7674
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• 2013

Background: The hypothesis that patients who primarily progress on two consecutive chemotherapy regimens without evidence of clinical benefit may opt for supportive care was investigated. The purpose was to determine the quality of life in recurrent ovarian cancer patients choosing to receive salvage chemotherapy in addition to supportive care or palliative care alone. A secondary objective was to evaluate factors that affect quality of life in ovarian cancer patients. Materials and Methods: A descriptive study was conducted in patients who had histological confirmed epithelial ovarian cancer and failed to respond to at least one regimen of chemotherapy, coming for treatment at the King Chulalongkorn Memorial Hospital in Bangkok, Thailand over a six-month period from August 2012-March 2013. Each patient was asked to complete the FACT-G and a general personal questionnaire. The median quality of life score was analyzed. The Mann Whitney U Test was used to compare the difference between salvage chemotherapy and palliative care groups, and the Kruskal Wallis was used to evaluate other variables. Results: Thirty-eight ovarian cancer patients were identified who failed to respond to chemotherapy. Of the 38, 30 chose salvage chemotherapy and eight palliative care for further treatment. By histology the carcimnomas were predominantly endometrioid subtype and poorly differentiated. The majority of patients in this study had FIGO stage III, and ECOG status 0-1. The median quality of life score was 76.3 (35.8-94.0), with no significant differences between the groups. Factors associated with the quality of life were the ECOG score and number of chemotherapeutic courses. Conclusions: In the setting of refractory or recurrent epithelial ovarian cancer, patients who receive salvage chemotherapy have comparable quality of life scores with patients treated with palliative care alone, providing a contrast with previous studies.

• BMB Reports
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• 제53권12호
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• pp.622-627
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• 2020

Cancer stem cells (CSCs) or tumor-initiating cells are thought to play critical roles in tumorigenesis, metastasis, drug resistance, and tumor recurrence. For the diagnosis and targeted therapy of CSCs, the molecular identity of biomarkers or therapeutic targets for CSCs needs to be clarified. In this study, we identified CD166 as a novel marker expressed in the sphere-forming CSC population of A2780 epithelial ovarian cancer cells and primary ovarian cancer cells. The CD166+ cells isolated from A2780 cells and primary ovarian cancer cells highly expressed CSC markers, including ALDH1a1, OCT4, and SOX2, and ABC transporters, which are implicated in the drug resistance of CSCs. The CD166+ cells exhibited enhanced CSC-like properties, such as increased sphere-forming ability, cell migration and adhesion abilities, resistance to conventional anticancer drugs, and high tumorigenic potential in a xenograft mouse model. Knockdown of CD166 expression in the sphere-forming ovarian CSCs abrogated their CSC-like properties. Moreover, silencing of CD166 expression in the sphere-forming CSCs suppressed the phosphorylation of focal adhesion kinase, paxillin, and SRC. These results suggest that CD166 plays a key role in the regulation of CSC-like properties and focal adhesion kinase signaling in ovarian cancer.

• BMB Reports
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• 제52권3호
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• pp.226-226
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• 2019

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7237-7242
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• 2015

Background: Epithelial ovarian cancer (EOC) is the commonest malignancy involving the ovaries. Maximum surgical cytoreduction (MCR) followed by adjuvant taxane-platinum chemotherapy are the standard of care treatments. Aims: To study treatment outcomes of EOC patients that were maximally cyto-reduced and received adjuvant paclitaxel-carboplatin (PC) chemotherapy. Materials and Methods: This retrospective cohort study included 174 patients with EOC treated at the Egyptian National Cancer Institute between 2006 and 2010. For inclusion, they should have had undergone MCR with no-gross residual followed by adjuvant PC chemotherapy. MCR was total abdominal hysterectomy/bilateral salpingo-oophorectomy [TAH/BSO] or unilateral salpingo-oophorectomy [USO] plus comprehensive staging. Results: The median age was 50 years. Most patients were married (97.1%), had offspring (92.5%), were postmenopausal (53.4%), presented with abdominal/pelvic pain and swelling (93.7%), had tumors involving both ovaries (45.4%) without extra-ovarian extension i.e. stage I (55.2%) of serous histology (79.9%) and grade II (87.4%). TAH/BSO was performed in 97.7% of cases. A total of 1,014 PC chemotherapy cycles were administered and were generally tolerable with 93.7% completing 6 cycles. Alopecia and numbness were the commonest adverse events. The median follow up period was 42 months. The 2-year rates for disease free survival (DFS) and overall survival (OS) were 70.7% and 94.8%, respectively. The respective 5-year rates were 52.6% and 81.3%. Advanced stage and high-grade were significantly associated with poor DFS and OS (p<0.001). Age >65 years was associated with poor OS (p =0.008). Using Cox-regression, stage was independent predictor of poor DFS and OS. Age was an independent predictor of poor OS.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10837-10840
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• 2015

To assess survival outcomes in a retrospective study, recurrent epithelial ovarian cancer patients were divided into three groups according to the platinum free interval as follows: platinum refractory that included the patients with tumor progression during treatment; platinum resistant and platinum sensitive that included the patients with tumor progression less than or more than six months, respectively. Clinical data for tumor progression in epithelial ovarian cancer patients treated at Chiang Mai University Hospital between January, 2006 and December, 2010 were reviewed. Thirty-nine patients were in the platinum refractory group while 27 were in the platinum resistant group and 75 in the platinum sensitive group. The mean age, the parity, the administration of neoadjuvant chemotherapy and the serous type did not significantly different across groups while the mean total number of chemotherapy regimens, the early stage patients, the patients with complete surgery and the surviving patients were significant more frequent in the platinum sensitive group. Regarding subsequent treatment after tumor recurrence, 87.2% underwent chemotherapy. With the median follow up time at 29 months, the median overall survival rates were 20 months, 14 months and 42 months in platinum refractory, platinum resistant and platinum sensitive groups, respectively (p<0.001). In addition, when the platinum sensitive patients developed the next episode of tumor progression, the median progression free interval time was only three to four months. In conclusion, the outcomes for platinum refractory the and platinum resistant groups was poorer than the platinum sensitive group. However, subsequent progression in the platinum sensitive group was also associated with a poor outcome.

• Reproductive and Developmental Biology
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• 제37권1호
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• pp.41-49
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• 2013

Ovarian cancer is the most lethal world-wide gynecological disease among women due to the lack of molecular biomarkers to diagnose the disease at an early stage. In addition, there are few well established relevant animal models for research on human ovarian cancer. For instance, rodent models have been established through highly specialized genetic manipulations, but they are not an excellent model for human ovarian cancer because histological features are not comparable to those of women, mice have a low incidence of tumorigenesis, and they experience a protracted period of tumor development. However, the laying hen is a unique and highly relevant animal model for research on human ovarian cancer because they spontaneously develop epithelial cell-derived ovarian cancer (EOC) as occurs in women. Our research group has identified common histological and physiological aspects of ovarian tumors from women and laying hens, and we have provided evidence for several potential biomarkers to detect, monitor and target for treatment of human ovarian cancers based on the use of both genetic and epigenetic factors. Therefore, this review focuses on ovarian cancer of laying hens and relevant regulatory mechanisms, based on genetic and epigenetic aspects of the disease in order to provide new information and to highlight the advantages of the laying hen model for research in ovarian carcinogenesis.

• 생명과학회지
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• 제27권7호
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• pp.834-839
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• 2017

Propolis는 꿀벌들이 나무로부터 수집한 천연물로서 항산화, 항염증, 항암 효과를 가지고 있어 전통의학에서 사용되고 있으며, 이러한 생리활성은 여러 가지 유용성분들이 혼합된 것과 관련이 있다. 난소암은 우리나라 여성에서 두 번째로 발병률이 높은 암이다. 대부분의 난소암 환자들은 초기에 수술적 기법과 항암요법에 우수하게 반응하지만, 항암제 내성에 의한 재발이 발생하게 되면 항암요법제에 의한 반응률이 매우 저조하여 높은 사망률을 보인다. 따라서, 난소암의 높은 치사율을 극복하기 위한 새로운 치료제 및 항암보조제의 개발이 필요하다. 본 연구에서는 인체 상피성 난소암 세포주인 A2780를 이용하여 Austalian propolis의 항암 효과와 활성기전을 조사하였다. Propolis 추출물은 농도 의존적으로 난소암 세포의 증식을 억제했으며. Flow cytometric 분석을 통해 G0/G1기에서 세포 주기 억제와 apoptosis 유도 효과를 확인하였다. 이러한 결과는 Austalian propolis의 인간 난소암에 대한 예방과 치료를 위한 보조제로서의 가능성을 제시한다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.2131-2135
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• 2013

Background: To evaluate the efficacy and safety of distearoylphosphatidylcholine pegylated liposomal doxorubicin (DPLD) combined with carboplatin for the treatment of platinum resistant or refractory epithelial ovarian cancer (EOC) or fallopian tube cancer. Materials and Methods: A retrospective analysis of women who received DPLD with carboplatin for recurrent EOC or fallopian tube cancer in King Chulalongkorn Memorial Hospital Thailand from January 2006 to August 2011 was conducted. Patients were identified from the medical records and data on demographic factors, stage, histology, surgical findings, cytoreduction status, and prior chemotherapies were abstracted. The efficacy and toxicity of DPLD/carboplatin were evaluated. Progression-free (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: A total of 65 patients, 64 with platinum resistant or refractory epithelial ovarian cancer and 1 with fallopian tube cancer, were enrolled. DPLD and carboplatin were given for an average of 4.46 cycles per patient with a total of 273 cycles. Among the 65 evaluable patients, 0% achieved CR, 7.69% PR, 15.4% SD and 76.% PD. The overall response rate was 23.1%. With a median follow-up of 27.4 months, the median progression-free and median overall survival in the 36 patients was 4.46 months and 8.76 months respectively. In the aspect of side effects, palmar-plantar erythrodysesthesia (PPE) occurred in 33.3% (Grade I 22.2%, Grade II 11.1%) and mucositis in 41.7% (Grade I 27.8%, Grade II 13.9%) of all treatment cycles, all Grade 1 or 2. Anemia, leukopenia and thrombocytopenia occurred in 58.3% (Grade I 41.7%, Grade II 16.7%), 66.7% (Grade I 47.2%, Grade II 19.4%), and 22.2% (Grade I 16.6%, Grade II 5.56%) of cycle respectively, and were mostly Grade 1 or 2. Conclusions: DPLD, the second-generation PLD drug combined with carboplatin every 4 weeks, is effective and has low toxicity for treatment of patients with recurrent platinum-resistant or refractory epithelial ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.101-105
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• 2014

Background and Purpose: Human epididymis protein 4 (HE4) has been suggested to be a novel biomarker of epithelial ovarian cancer (EOC). The present study aimed to evaluate and compare HE4 with the commonly used marker, carbohydrate antigen 125 (CA125), in prediction and therapy-monitoring of EOC. Patients and Methods: Serum HE4 concentrations from 123 ovarian cancer patients and 174 controls were measured by Roche electrochemiluminescent immunoassay (ECLIA). Risk of ovarian malignancy algorithm (ROMA) values were calculated and assessed. In addition, the prospects of HE4 detection for therapy-monitoring were evaluated in EOC patients. Results: The ROMA score could classify patients into high- and low-risk groups with malignancy. Indeed, lower serum HE4 was significantly associated with successful surgical therapy. Specifically, 38 patients with EOC exhibited a greater decline of HE4 compared with CA125. In contrast, elevation of HE4 better predicted recurrence (of 46, 11 patients developed recurrence, and with it increased HE4 serum concentrations) and a poor prognosis than CA125. Conclusions: This study suggests that serum HE4 levels are closely associated with outcome of surgical therapy and disease prognosis in Chinese EOC patients.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5883-5890
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• 2013

Previously, we demonstrated overexpression of semaphorin4D (SEMA4D, CD100) to be closely related to tumor angiogenesis in epithelial ovarian cancers (EOCs). However, the function and expression of SEMA4D in the EOC microenvironment has yet to be clarified in detail. In this study, we confirmed that overexpression of SEMA4D in primary tumors and ascites was related to low differentiation, platinum resistance and a refractory status (P<0.05), while high M2 macrophage count and percentage were evident in EOC patients with advanced FIGO stage and platinum resistance (P<0.05), using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and fluorescence-activated cell sorting (FACS), respectively. The data showed correlations of SEMA4D expression and M2 macrophage counts in primary tumors and M2 macrophage percentage in ascites (r=0.281 and 0.355, each P<0.05). In the Cox proportional hazard mode, SEMA4D expression was an independent indicator of overall survival (OS) and progression-free survival (PFS) for EOC patients. Furthermore, higher expression of SEMA4D in ovarian cancer cell lines (SKOV3, A2780, and SW626) and their supernatants were found than that in a human primary cultured ovarian cell and its supernatant by reversed transcript PCR (RT-PCR), Western blotting and ELISA, respectively. Interestingly, peripheral blood monocytes (MOs) tended towards the M2-polarized macrophage phenotype ($CD163^{high}$) in vitro after human recombined soluble SEMA4D protein stimulation. These findings suggest that SEMA4D might possibly serve as a reliable tool for early and accurate prediction of EOC poor prognosis and could playan important role in promoting tumor dissemination and metastasis in the EOC microenvironment. Thus SEMA4D and its role in macrophage polarization in EOC warrants further study.