• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2177-2183
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• 2016

Background: To evaluate the predictive role of a risk of malignancy index in discriminating between benign and malignant adnexal masses preoperatively. Materials and Methods: A total of 408 patients with adnexal masses managed surgically between January 2010 and February 2014 were included. The risk of malignancy indices (RMI) 1, 2, 3 and 4 were calculated using findings for ultrasonography, menopausal status, and CA125 levels. Histopathologic results were the end point. ROC analysis was used for the sensitivity and the specificity of the models. Results: Some 37.6 % of the cases were malignant in the postmenopausal group while 7.9 % were malignant in the premenopausal group. Pelvic pain was the most common complaint, and the majority of the cases were diagnosed at stage 3. The RMI 1, 2, 3 and 4 yielded percentage sensitivities of 76.1, 79.1, 76.1 and 76.1 and specificities of 91.5, 89.1, 90.6, 88.6, respectively. RMI 1 was the most reliable test in the general population according to AUC levels and Kappa statistics. From ROC analysis results of post/premenopausal women, the RMI 1 (cut off: 200) yielded sensitivities of 84.0/60.9 and specificities of 87.7/92.5. With RMI 2 they were 88.6/60.9 and 80.0/91.0, with RMI 3 84.0/60.9 and 87.7/91.8, and with RMI 4 (cut off:400) 81.8/47.8 and 83.6 /44.0. Although test performance of RMI methods were good in a general population and postmenopausal women, the RMI inter-agreement validity was only moderate or fair in premenopausal women. Conclusions: Our study confirms the effectiveness of RMI algorithms in postmenopausal women. However, more sensitive tests are needed for premenopausal women.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5811-5814
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• 2014

Background: To investigate abnormal cervical histopathology (ACH) from hysterectomy specimens with normal preoperative Papanicolaou (Pap) smears. Materials and Methods: Medical records from May 2009 to April 2012 were retrospectively reviewed of subjects from whom hysterectomy specimens were taken in Thammasat University Hospital. All had normal preoperative Pap smears. ACH was the primary outcome. A p-value less than 0.05 was considered significant. A total of 483 subjects with an average age of 50.5 years were recruited. Benign cases of enlarged uterus and pelvic mass were present in 94% (430/483). Endometrial and ovarian cancer were found at 6.2 and 4.7%, respectively. In hysterectomy specimens there were 19 (4%) cases of ACH. Silent ACH with benign disease, endometrial and ovarian cancers were 1.2% (5/430), 33.3% (10/30) and 17.4% (4/23), respectively. The negative predictive value (NPV) and false negative rate of Pap smears were 96 and 4%, respectively. ACH in malignant cases were 27.9% (12/43) and 20% (2/10) in adequate (APS) and inadequate (IPS) Pap collection groups, respectively. ACH in benign condition were 0.68% (2/292) and 2.2% (3/138) in APS and IPS, respectively. ACH was more often found in hysterectomy specimens with indication of malignancy than benign conditions with statistical significance. One third of preoperative stage I endometrial cancer cases had cervical involvement. Conclusions: Silent ACH in normal preoperative Pap smear was 4 %. Inadequate Pap smear collection is still the major problem in this study. Reducing inadequate Pap smear collection could reduce the false negative rate.

• Molecules and Cells
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• v.44 no.7
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• pp.481-492
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• 2021

Tribbles homolog 2 (TRIB2) is implicated in tumorigenesis and drug resistance in various types of cancers. However, the role of TRIB2 in the regulation of tumorigenesis and drug resistance of cancer stem cells (CSCs) is still elusive. In the present study, we showed increased expression of TRIB2 in spheroid-forming and aldehyde dehydrogenase-positive CSC populations of A2780 epithelial ovarian cancer cells. Short hairpin RNA-mediated silencing of TRIB2 expression attenuates the spheroid-forming, migratory, tumorigenic, and drug-resistant properties of A2780 cells, whereas overexpression of TRIB2 increases the CSC-like characteristics. TRIB2 overexpression induced GSK3β inactivation by augmenting AKT-dependent phosphorylation of GSK3β at Ser9, followed by increasing β-catenin level via reducing the GSK3β-mediated phosphorylation of β-catenin. Treatment of TRIB2-ovexpressed A2780 cells with the phosphoinositide3-kinase inhibitor LY294002 abrogated TRIB2-stimulated proliferation, migration, drug resistance of A2780 cells. These results suggest a critical role for TRIB2 in the regulation of CSC-like properties by increasing the stability of β-catenin protein via the AKT-GSK3β-dependent pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1709-1710
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• 2012

Cancer is a major public health problem in Indonesia, becoming the 7th largest cause of death based on a national survey in 2007, accounting for 5.7 of all mortality. A cancer registry was started in 1970, but it was partial and was stopped mainly because no government body was responsible. Realizing the above situation, the Indonesian government established the Sub Directorate of Cancer Control within the Ministry of Health, with responsibility for developing a national cancer control program, including a cancer registry. A sustainable cancer registry was then started in 2007 within Jakarta Province, first hospital-based but then expanded to be population-based. Steps of cancer registration in Jakarta are data collection, data verification, data validation, data management and analysis, and data publication. Data collection is conducted by health facilities (hospitals, laboratories, primary health centers) at the district/municipal level, with reports to the provincial level. Data are collected passively by holding meetings every three months in the district/municipality. Verification of data is the responsibility of the medical doctor or pathologist in each data source. Data validation is conducted by a team in the cancer registry, consisting of district/municipal/province health officers, pathologists, and registrars. Data management and analyses are conducted by a cancer registry team at the provincial level, assisted by the national team. We use software named Indonesian Cancer Registry System (SRIKANDI) which is adopted from CanReg4 IARC. Data from the population-based cancer registry in Jakarta Province showed the leading cancers among females in 2005-2007 to be breast cancer, cervical cancer, ovarian cancer, colorectal cancer and among males are bronchus and lung cancer, colorectal cancer, liver cancer, pharyngeal cancer, and prostate cancer. The leading childhood cancers are leukaemia and retinoblastoma.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2271-2275
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• 2016

Background: The value of 5-aminolevulinic acid (ALA) in fluorescence detection of peritoneal metastases and the underlying mechanisms were evaluated in patients with peritoneal surface malignancies. Materials and Methods: Oral 5-ALA was administered at a concentration of 20 mg/kg body weight with 50 ml of water 2 hours prior to surgery (n=115). The diagnostic value of 5-ALA based fluorescence production was evaluated following white light inspection during prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Then, peptide transporter PEPT1 (ALA influx transporter) and ATP-binding cassette transporter ABCG2 (porphyrin efflux transporter) gene expression was determined with quantitative real time (qRT)-PCR and pathological diagnoses confirmed for all tissue samples. Results: The 5-ALA based photodynamic detection rate was 17% for appendiceal mucinous neoplasms, 54% for colorectal cancers, 33% for gastric cancers, 67% for diffuse malign peritoneal mesotheliomas, and 89% for epithelial ovarian cancer of peritoneal metastases. 5-ALA was detected in all cases of peritoneal metastases originating from cholangiocarcinomas whereas it was not able to detect any in granulosa cell and gastrointestinal stromal tumor cases. Furthermore, PEPT1 was overexpressed whereas ABCG2 expression was downregulated in tumors detected with fluorescence. Conclusions: 5-ALA provided 100% specificity and high sensitivity to detect peritoneal metastases in subgroups of patients with peritoneal surface mailgnancies. ALA influx transporter PEPT1 and porphyrin efflux transporter ABCG2 genes are important in tumor specific 5-ALA induced fluorescence in vivo. Further studies should clarify diagnostic utility of 5-ALA in peritoneal surface malignancies.

• Journal of Korean Neurosurgical Society
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• v.59 no.4
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• pp.392-399
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• 2016

Objective : Brain metastases in gynecologic cancer (ovarian, endometrial, and cervical cancer) patients are rare, and the efficacy of Gamma Knife Radiosurgery (GKRS) to treat these had not been evaluated. We assessed the efficacy of GKRS and prognostic factors for tumor control and survival in brain metastasis from gynecologic cancers. Methods : This retrospective study was approved by the institutional review board. From May 1995 to October 2012, 26 women (mean age 51.3 years, range 27-70 years) with metastatic brain tumors from gynecologic cancer were treated with GKRS. We reviewed their outcomes, radiological responses, and clinical status. Results : In total 24 patients (59 lesions) were available for follow-up imaging. The median follow-up time was 9 months. The mean treated tumor volume at the time of GKRS was $8185mm^3$ (range $10-19500mm^3$), and the median dose delivered to the tumor margin was 25 Gy (range, 10-30 Gy). A local tumor control rate was 89.8% (53 of 59 tumors). The median overall survival was 9.5 months after GKRS (range, 1-102 months). Age-associated multivariate analysis indicated that the Karnofsky performance status (KPS), the recursive partitioning analysis (RPA) classification, and the number of treated lesions were significant prognostic factors for overall survival (HR=0.162, p=0.008, HR=0.107, p=0.038, and HR=2.897, p=0.045, respectively). Conclusion : GKRS is safe and effective for the management of brain metastasis from gynecologic cancers. The clinical status of the patient is important in determining the overall survival time.

• YAKHAK HOEJI
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• v.60 no.3
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• pp.128-134
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• 2016

L1 cell adhesion molecule (L1CAM) is a cell surface molecule to initiate a variety of cellular responses through interacting with other cell adhesion molecules in a homophilic or heterophilic manner. Although its expression was found to be upregulated in some tumor cells, including cholangiocarcinomas, and ovarian cancers, and many studies have investigated the role of L1CAM in these cancers, its role in inflammatory responses has been poorly understood. In this study, we explored the role of L1CAM in macrophage-mediated inflammatory responses. L1CAM significantly suppressed the production of nitric oxide (NO), but induced cell proliferation in RAW264.7 cells. L1CAM expression was detectable, but its expression was markedly decreased by lipopolysaccharide (LPS) in RAW264.7 cells. In addition, the expression of pro-inflammatory genes, such as tumor necrosis factor (TNF)-${\alpha}$, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) induced by LPS was dramatically suppressed by L1CAM in RAW264.7 cells. L1CAM inhibited the transcriptional activities of NF-${\kappa}B$ and AP-1 while its cytoplasmic domain deletion form, $L1{\Delta}CD$ did not suppressed their activities in RAW264.7 cells. Moreover, L1CAM suppressed nuclear translocation of p65 and p50 as well as c-Jun, c-Fos and p-ATF2 which are transcription factors of NF-${\kappa}B$ and AP-1, respectively. In conclusion, L1CAM suppressed inflammatory responses in macrophages through inhibiting NF-${\kappa}B$ and AP-1 pathways.

• Bulletin of the Korean Chemical Society
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• v.23 no.8
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• pp.1139-1143
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• 2002

Analysis of lysophosphatidic acids (LPAs) is of clinical importance as they can serve a potential marker for ovarian and other gynecological cancers and obesity. It is critically important to develop a highly sensitive and specific method for the early detection of gynecological cancers to improve the overall outcome of this disease. We have established a novel quantification method of LPAs in human plasma by negative ionization tandem mass spectrometry (MS-MS) using multiple reaction monitoring (MRM) mode without the conventional TLC step. Protein-bound lipids, LPAs in plasma were extracted with methanol : chloroform (2:1) containing LPA C14:0 as an internal standard under acidic condition. Following back extraction with chloroform and water, the centrifuged lower phase was evaporated and reconstituted in methanol. The reconstituted solution was directly injected into electrospray source of MS/MS. For MRM mode, Q1 ions selected were m/z 409, 433, 435, 437 and 457 which corresponds to molecular mass [M-H]- of C16:0, C18:2, C18:1, C18:0 and C20:4 LPA, respectively. Q2 ions selected for MRM were m/z 79, phosphoryl product. Using MS/MS with MRM mode, all the species of LPAs were completely separated from plasma matrix without severe interferences. This method allowed simultaneous detection and quantification of different species of LPAs in a plasma over a linear dynamic range of 0.01-25 ㎛olL-1 . The detection limit of the method was 0.3 pmol/mL, with a correlation coefficient of 0.9983 in most LPAs analyzed. When applied to the plasmas of normal and gynecological cancer patients, this new method differentiated two different groups by way of total LPA level.

• Toxicological Research
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• v.27 no.4
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• pp.253-259
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• 2011

Transforming growth factor ${\beta}$ (TGF-${\beta}$) is involved in cellular processes including growth, differentiation, apoptosis, migration, and homeostasis. Generally, TGF-${\beta}$ is the inhibitor of cell cycle progression and plays a role in enhancing the antagonistic effects of many growth factors. Unlike the antiproliferative effect of TGF-${\beta}$, E2, an endogeneous estrogen, is stimulating cell proliferation in the estrogen-dependent organs, which are mediated via the estrogen receptors, $ER{\alpha}$ and $ER{\beta}$, and may be considered as a critical risk factor in tumorigenesis of hormone-responsive cancers. Previous researches reported the cross-talk between estrogen/$ER{\alpha}$ and TGF-${\beta}$ pathway. Especially, based on the E2-mediated inhibition of TGF-${\beta}$ signaling, we examined the inhibition effect of 4-tert-octylphenol (OP) and 4-nonylphenol (NP), which are well known xenoestrogens in endocrine disrupting chemicals (EDCs), on TGF-${\beta}$ signaling via semi-quantitative reverse-transcription PCR. The treatment of E2, OP, or NP resulted in the downregulation of TGF-${\beta}$ receptor2 (TGF-${\beta}$ R2) in TGF-${\beta}$ signaling pathway. However, the expression level of TGF-${\beta}1$ and TGF-${\beta}$ receptor1 (TGF-${\beta}$ R1) genes was not altered. On the other hand, E2, OP, or NP upregulated the expression of a cell-cycle regulating gene, c-myc, which is a oncogene and a downstream target gene of TGF-${\beta}$ signaling pathway. As a result of downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc, E2, OP, or NP increased cell proliferation of BG-1 ovarian cancer cells. Taken together, these results suggest that E2 and these two EDCs may mediate cancer cell proliferation by inhibiting TGF-${\beta}$ signaling via the downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc oncogene. In addition, it can be inferred that these EDCs have the possibility of tumorigenesis in estrogen-responsive organs by certainly representing estrogenic effect in inhibiting TGF-${\beta}$ signaling.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2529-2532
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• 2013

Background: Pelvic exenteration is a procedure which includes enbloc resection of pelvic organs followed by surgical reconstruction. Aims include both cure and palliation but data for pelvic exenteration in Thailand are very limited. Objective: This study was conducted to evaluate characteristics of patients, operative procedure outcomes and complications. Materials and Methods: This retrospective review covered all of the charts of exenteration patients during January 2002 to December 2011. Baseline characteristic of the patients were collected as well as details of clinical results. Results: A total of 13 cases of pelvic exenteration were included. Most underwent total pelvic exenteration (9 cases) and the remainder posterior and anterior exenteration. Their primary cancers were ovarian, cervical and vulva. Mean operative time was 532 minutes (SD 160.2, range 270-750) and estimated blood loss was 2830 ml (1850, 1000-8000). Mean tumor size was 7.33 cm (3.75, 4-15). Mean hospital stay was 35.2 days (29.8, 13-109). The most common post operative complication was urinary tract infection. Overall disease free survival with a negative surgical margin was significantly better than in positive surgical margin patients (p=0.014). Conclusions: Surgical margin was the most significant prognostic factor for disease free survival, in line with earlier studies.