• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.933-939
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• 2015

Malignant tumors are often accompanied by increased risk of hematological abnormalities. However, few studies have reported any prognostic impact of preoperative thrombocytosis, leukocytosis and anemia in epithelia ovarian cancer (EOC). This study aimed to investigate preoperative hematological parameters for anemia, leukocytosis and thombocytosis in relation to established prognostic factors and survival in EOC cases. A total of 816 Chinese women treated for EOC were retrospectively included in the study focusing on the relationship between preoperative hemoglobin, leukocyte and platelet counts, and a panel of clinicopathologic characteristics and outcome. Preoperative anemia was present in 13.4%, leukocytosis in 16.7% and thrombocytosis in 22.8%. Additionally, EOC patients with low differentiation grade, advanced stage, lymph node (LN) metastasis, residual disease ${\geq}1cm$, ascites volume >1,000ml, serum cancer antigen 125 (CA125) >675U/ml, and disease recurrence had the higher prevalence of preoperative anemia, leukocytosis and thrombocytosis (all p<0.05). Moreover, EOC patients with older age or postmenopausal EOC patients had the higher prevalence of thrombocytosis (28.7% vs 17.3% or 26.0% vs 17.7%). Furthermore, in a Cox proportional hazard model, thrombocytosis was an independent factor for progression-free survival (PFS) and overall survival (OS) (p<0.001). Conclusively, preoperative anemia, leukocytosis or thrombocytosis in EOC patients is closely associated with more malignant disease phenotype and poorer prognosis. Significantly, thrombocytosis may independently predict the disease-specific survival for EOC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3977-3982
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• 2012

Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In this study, we assessed the anticancer effects of valproic acid (VPA) on ovarian cancer in vitro and in vivo. Cultured SKOV3 cells were treated by VPA with different concentrations and time, then the effects on cell growth, cell cycle, apoptosis, and related events were investigated. A human ovarian cancer model transplanted subcutaneously in nude mice was established, and the efficacy of VPA used alone and in combination with diammine dichloroplatinum (DDP) to inhibit the growth of tumors was also assessed. Proliferation of SKOV3 cells was inhibited by VPA in a dose and time dependent fashion. The cell cycle distribution changed one treatment with VPA, with decrease in the number of S-phase cells and increase in G1-phase. VPA could significantly inhibit the growth of the epithelial ovarian cancer SKOV3 cells in vivo without toxic side effects. Treatment with VPA combined with DDP demonstrated enhanced anticancer effects. The result of flow cytometry (FCM) indicated that after VPA in vitro and in vivo, the expression of E-cadherin was increased whereas vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were decreased. This study suggests that VPA could be a novel attractive agent for treatment of ovarian cancer.

• BMB Reports
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• v.43 no.8
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• pp.554-560
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• 2010

Smad4 is involved in cancer progression and metastasis. Using a pair of human syngeneic epithelial ovarian cancer cells with low (HO-8910) and high (HO-8910PM) metastatic abilities, we aimed to reveal the role of Smad4 in ovarian cancer metastasis in vitro. Smad4 was down-regulated in HO-8910PM cell line relative to HO-8910 by implicating Smad4 was probably a potential tumor suppressor gene for ovarian cancer. Re-expression of Smad4 decreased the migration ability and inhibited the invasion capacity of HO-8910PM, while promoted the cell adhesion capacity for HO-8910PM. The stable expression of Smad4 increased the expression of E-cadherin, reduced the expression of plasminogen activator inhibitor-1 (PAI-1) and slightly down-regulated the expression of VEGF. Smad4 suppresses human ovarian cancer cell metastasis potential through its effect on the expressions of PAI-1, E-cadherin and VEGF. Results from current work implicate Smad4 might suppress the invasion and metastasis of human ovarian tumor cells through a TGF-$\beta$/Smad-mediated pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4787-4790
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• 2015

Objective: To review ovarian cancer cases in children and adolescents in Siriraj Hospital and assess the prognosis, recurrence of disease, and reproductive outcomes after treatment. Materials and Methods: A retrospective descriptive study was conducted in ovarian cancer patients 21 years and younger who had been treated at Siriraj Hospital between January 1990 and December 2009. Medical records were reviewed and relevant data were recorded. Results: A total of 48 cases met the criteria; their mean age was 16.4 years. Abdominal distension was the major symptom. 91.6% were germ cell tumors and the remaining cases were sex cord-stromal and epithelial tumors. More than half (25/48 cases) presented with stage I disease. The most common used chemotherapy regimen for germ cell tumors was BEP (bloemycin, etoposide, cisplatin). Most of patients had favorable outcomes; 46/48 cases had complete remission and retained their good health at the time of the review. We had only one recurrent case and one dead case. Ten of contacted patients had married and 3 of them had successful full-term pregnancies. Conclusions: Ovarian malignancy in children and adolescents is a rare disease. The authors reported 48 cases in 20 year-period of work. Most of them have favorable outcomes. Return of ovarian function and fertility are the topics of interest.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7561-7568
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• 2013

Galectin-3 (Gal-3) is a carbohydrate-binding protein which is thought to be involved in cancer progression but its contribution to epithelial ovarian cancer (EOC) remains unclear. The present study sought to determine the role of Gal-3 in chemoresistance of the human SKOV-3 ovarian cancer cell line to paclitaxel (PTX) using recombinant human Gal-3 (rhGal-3) and PectaSol-C modified citrus pectin (Pect-MCP) as a specific Gal-3 competitive inhibitor. Our results showed 41% increased cell proliferation, 36% decreased caspase-3 activity and 33.6% increased substrate-dependent adhesion in the presence of rhGal-3 compared to the control case (p<0.001). Treatment of cells with a non-effective dose of PTX (100nM) and 0.1% Pect-MCP in combination revealed synergistic cytotoxic effects with 75% reduced cell viability and subsequent 3.9-fold increase in caspase-3 activity. Moreover, there was 39% decrease in substrate-dependent adhesion compared to control (p<0.001). These results suggest that inhibition of Gal-3 could be a useful therapeutic tool for combination therapy of ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.323-333
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• 2016

Background: Ovarian cancer remains a major worldwide health care issue due to the lack of satisfactory diagnostic methods for early detection of the disease. Prior studies on the role of serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in detecting ovarian cancer presented conflicting results. New tools to improve the accuracy of identifying malignancy are urgently needed. We here aimed to evaluate the diagnostic utility of tissue CA125 and HE4 gene expression in comparison to serum CA125 and HE4 in discriminating benign from malignant pelvic masses. Materials and Methods: One-hundred Egyptian women were enrolled in this study, including 60 epithelial ovarian cancer (EOC) patients and 20 benign ovarian tumor patients, as well as 20 apparently healthy women. Preoperative serum levels of CA125 and HE4 were measured by immunoassays. Tissue expression levels of genes encoding CA125 and HE4 were determined by quantitative real time polymerase chain reaction (qRT-PCR). The diagnostic performance of CA125 and HE4, measured either as mRNA or protein levels, was evaluated by receiver operating characteristic (ROC) curves. Results: The serum CA125+HE4 combination and serum HE4, with area under the curve (AUC) values of 0.935 and 0.932, respectively, performed significantly better than serum CA125 (AUC=0.592; P<0.001). Tissue CA125 and HE4 (AUC=1) performed significantly better than serum CA125 (P<0.001), serum HE4 (P=0.016) and the serum CA125+HE4 combination (P=0.018). Conclusions: Measurement of tissue CA125 and HE4 gene expression not only improves discriminatory performance, but also broadens the range of differential diagnostic possibilities in distinguishing EOC from benign ovarian tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4829-4837
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• 2014

The present systematic review and meta-analysis was conducted to assess any association between breastfeeding and the risk of ovarian cancer. A systematic search of published studies was performed in PUBMED and EMBASE and by reviewing reference lists from retrieved articles through March 2013. Data extraction was conducted independently by two authors. Pooled relative risk ratios were calculated using random-effect models. Totals of 5 cohort studies and 35 case-control studies including 17,139 women with ovarian cancer showed a 30% reduced risk of ovarian cancer when comparing the women who had breastfed with those who had never breastfed (pooled RR = 0.70, 95% CI: 0.64-0.76; p = 0.00), with significant heterogeneity in the studies (p = 0.00; I2 = 76.29%). A significant decreasd in risk of epithelial ovarian cancer was also observed (pooled RR = 0.68, 95% CI: 0.61-0.76). When the participants were restricted to only parous women, there was a slightly attenuated but still significant risk reduction of ovarian cancer (pooled RR = 0.76, 95% CI: 0.69-0.83). For total breastfeeding duration, the pooled RRs in the < 6 months, 6-12 months and > 12 months of breastfeeding subgroups were 0.85 (95% CI: 0.77-0.93), 0.73 (95% CI: 0.65-0.82) and 0.64 (95%CI: 0.56-0.73), respectively. Meta-regression of total breastfeeding duration indicated an increasing linear trend of risk reduction of ovarian cancer with the increasing total breastfeeding duration (p = 0.00). Breastfeeding was inversely associated with the risk of ovarian cancer, especially long-term breastfeeding duration that demonstrated a stronger protective effect.

• Journal of dental hygiene science
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• v.18 no.3
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• pp.188-193
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• 2018

The aim of the current study was to demonstrate the potential therapeutic efficacy of resveratrol in oral cancer patients. Lysophosphatidic acid (LPA) intensifies cancer cell invasion and metastasis, whereas resveratrol, a natural polyphenolic compound, possesses antitumor activity, suppressing cell proliferation and progression in various cancer cell lines (ovarian, gastric, oral, pancreatic, colon, and prostate cancer cells). In addition, resveratrol has been identified as an inhibitor of LPA-induced proteolytic enzyme expression and ovarian cancer invasion. Furthermore, resveratrol was shown to inhibit oral cancer cell invasion by downregulating hypoxia-inducible factor $1{\alpha}$ and vascular endothelial growth factor expression. Recently, we demonstrated that LPA is important for the expression of transcription factors TWIST and SLUG during epithelial-mesenchymal transition (EMT) in oral squamous carcinoma cells. In this study, we treated serum-starved cultures of oral squamous carcinoma cell line YD-10B with resveratrol for 24 hours prior to stimulation with LPA. To identify an optimal resveratrol concentration that does not induce apoptosis in oral squamous carcinoma cells, we determined the toxicity of resveratrol in YD-10B cells by assessing their viability using the MTT assay. Another assay was performed using Matrigel-coated cell culture inserts to detect oral cancer cell invasion activity. Immunoblotting was applied for analyzing protein expression of SLUG, TWIST1, E-cadherin, and GAPDH. We demonstrated that resveratrol efficiently inhibited LPA-induced oral cancer cell EMT and invasion by downregulating SLUG and TWIST1 expression. Therefore, resveratrol may potentially reduce oral squamous carcinoma cell invasion and metastasis in oral cancer patients, improving their survival outcomes. In summary, we identified new targets for the development of therapies against oral cancer progression and characterized the therapeutic potential of resveratrol for the treatment of oral cancer patients.

• Journal of Medicine and Life Science
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• v.20 no.1
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• pp.48-52
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• 2023

High-grade serous carcinoma (HGSC) is the most common type of pelvic cancer among women. Serous tubal intraepithelial carcinoma (STIC) is a precursor lesion of HGSC. Herein, we report a rare occurrence of STIC in patients undergoing surgery for benign indications without a family history of ovarian cancer. A 77-year-old woman underwent total laparoscopic hysterectomy and bilateral salpingo-oophorectomy for uterine prolapse. Pathological examination revealed bilateral STIC without ovarian abnormalities, and no other abnormal findings were noted. Another patient, a 49-year-old woman, underwent laparoscopic total hysterectomy and bilateral salpingectomy for uterine fibroids. STIC lesions were observed in both fallopian tubes. Subsequently, a staging was performed. No additional lesions were found, and the patient was followedup through imaging and blood tests. As reports of STIC lesions are rare, data on their clinical outcomes and management strategies are limited. In this report, we present cases of incidental STIC in benign surgery and discuss its proper interpretation and management. Through the early detection of STIC lesions, patients with risk factors can be identified in advance, which will allow prevention and early detection of ovarian cancer. Opportunistic salpingectomy was also actively discussed in this regard.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7267-7270
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• 2015

Introduction: Kelantan is one of the states in Malaysia which has a high prevalence of type 2 diabetes (DM2). Other than with endometrial carcinoma, the association of DM2 with particular female cancers is not known. Objective: To determine the proportion of breast, cervical, ovarian and endometrial cancers among females with DM2 diagnosed in Hospital Universiti Sains Malaysia (HUSM) over an 11 year period. Materials and Methods: All histologically confirmed cases of breast, endometrial, cervical and ovarian carcinomas admitted to the Hospital were included in the study. The patient diabetic status was traced from the hospital medical records. Results: There was a total of 860 cases of breast, cervical, ovarian and endometrial carcinomas over this period. Breast carcinoma was the commonest, accounting for 437/860 (50.8%) followed by cervix, 159/860 (18.5%), ovarian, 143/860 (16.6%) and endometrial carcinomas, 121/860 (14.1%). Out of these, 228/860 (26.5%) were confirmed diabetics. Endometrial carcinoma patients showed the highest proportion being diabetics, 42.1% (51/121), followed by ovarian cancer, 25.9% (37/143), breast carcinoma, 23.6% (103/437) and cervical cancer 23.3% (37/159). Conclusions: There is a significant proportion of DM2 among women with these four cancers, endometrial carcinoma being the highest followed by ovarian, breast and cervical carcinoma. The rising trend of these four cancers is in tandem with an increasing trend of DM2 in the community. In populations where diabetes is prevalent, screening for epithelial cancers should be rigourous. Diabetic clinics should include screening for these cancers among their female patients and gynecology clinics should screen the women they treat for their diabetes status.