Publications by authors named "Chiou-Chung Yuan"

61 Publications

Methylomics of nitroxidative stress on precancerous cells reveals DNA methylation alteration at the transition from to invasive cervical cancer.

Oncotarget 2017 Sep 6;8(39):65281-65291. Epub 2017 Jun 6.

Translational Epigenetics Center, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.

Epigenetic dysregulation is important in cervical cancer development, but the underlying mechanism is largely unknown. Increasing evidence indicates that DNA methylation is sensitive to changes in microenvironmental factors, such as nitric oxide (NO) in the chronic inflammatory cervix. However, the epigenomic effects of NO in cancer have not been investigated. In this study, we explored the methylomic effects of nitroxidative stress in HPV-immortalized precancerous cells. Chronic NO exposure promoted the acquisition of malignant phenotypes such as cell growth, migration, invasion, and anchorage-independent growth. Epigenetic analysis confirmed hypermethylation of . Whole-genome methylation analysis showed , , , , and were hypermethylated in cells. The hypermethylation , , , and was confirmed in cervical scrapings from invasive cancer, but not in CIN3/CIS, CIN2 and CIN1 (=0.019, 0.023, 0.023 and 0.027 respectively), suggesting the role in the transition from to invasive process. Our results reveal that nitroxidative stress causes epigenetic changes in HPV-infected cells. Investigation of these methylation changes in persistent HPV infection may help identify new biomarkers of DNA methylation for cervical cancer screening, especially for precancerous lesions.
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http://dx.doi.org/10.18632/oncotarget.18370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630330PMC
September 2017

An epigenetic signature of adhesion molecules predicts poor prognosis of ovarian cancer patients.

Oncotarget 2017 Aug 16;8(32):53432-53449. Epub 2017 Jun 16.

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Republic of China.

DNA methylation is a promising biomarker for cancer. The epigenetic effects of cell adhesion molecules may affect the therapeutic outcome and the present study examined their effects on survival in ovarian cancer. We integrated methylomics and genomics datasets in The Cancer Genome Atlas (n = 391) and identified 106 highly methylated adhesion-related genes in ovarian cancer tissues. Univariate analysis revealed the methylation status of eight genes related to progression-free survival. In multivariate Cox regression analysis, four highly methylated genes (, , , ) and three genes (, , ) with low methylation were significantly associated with poor progression-free survival. Low methylation of was an independent poor prognostic factor for overall survival after adjustment for age and stage. Patients who carried any two of , or were significantly associated with poor progression-free survival (hazard ratio: 1.59; 95% confidence interval: 1.23, 2.05). This prognostic methylation signature was validated in a methylomics dataset generated in our lab (n = 37, hazard ratio: 16.64; 95% confidence interval: 2.68, 103.14) and in another from the Australian Ovarian Cancer Study (n = 91, hazard ratio: 2.43; 95% confidence interval: 1.11, 5.36). Epigenetics of cell adhesion molecules is related to ovarian cancer prognosis. A more comprehensive methylomics of cell adhesion molecules is needed and may advance personalized treatment with adhesion molecule-related drugs.
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http://dx.doi.org/10.18632/oncotarget.18515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581121PMC
August 2017

4-Acetylantroquinonol B suppresses autophagic flux and improves cisplatin sensitivity in highly aggressive epithelial cancer through the PI3K/Akt/mTOR/p70S6K signaling pathway.

Toxicol Appl Pharmacol 2017 06 10;325:48-60. Epub 2017 Apr 10.

Department of Hematology and Oncology, Cancer Center, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Department of Medical Research & Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan. Electronic address:

Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg). Atg-5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P=0.027) and depleting Atg-5 in ES-2 cell lines significantly induced apoptosis. 4-AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin-resistance were more responsive to 4-AAQB. For the first time, we demonstrate that 4-AAQB significantly suppress Atg-5 and Atg-7 expression with decreased autophagic flux in ovarian cancer cells via inhibition of the PI3K/Akt/mTOR/p70S6K signaling pathway. Similar to Atg-5 silencing, 4-AAQB-induced autophagy inhibition significantly enhanced cell death in vitro. These results are comparable to those of hydroxychloroquine (HCQ). In addition, 4-AAQB/cisplatin synergistically induced apoptosis in ovarian cancer cells. In vivo, 4-AAQB/cisplatin also significantly induced apoptosis and autophagy in an ES-2 mouse xenografts model. This is the first report demonstrating the efficacy of 4-AAQB alone or in combination with cisplatin on the suppression of ovarian cancer via Atg-5-dependent autophagy. We believe these findings will be beneficial in the development of a novel anti-ovarian cancer therapeutic strategy.
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http://dx.doi.org/10.1016/j.taap.2017.04.003DOI Listing
June 2017

Bruton's tyrosine kinase (Btk) inhibitor ibrutinib suppresses stem-like traits in ovarian cancer.

Oncotarget 2015 May;6(15):13255-68

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

According to a Prognoscan database, upregulation of Bruton's tyrosine kinase (Btk) is associated with low overall survival in ovarian cancer patients. We found that spheroids-forming ovarian cancer cell, which highly expressed cancer stem-like cell (CSC) markers and Btk, were cisplatin resistant. We next treated CSCs and non-CSCs by a combination of ibrutinib and cisplatin. We found that chemoresistance was dependent on Btk and JAK2/STAT3, which maintained CSC by inducing Sox-2 and prosurvival genes. We suggest that addition of ibrutinib to cisplatin may improve treatment outcome in ovarian cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537012PMC
http://dx.doi.org/10.18632/oncotarget.3658DOI Listing
May 2015

DNA methylation as a biomarker for the detection of hidden carcinoma in endometrial atypical hyperplasia.

Gynecol Oncol 2014 Dec 23;135(3):552-9. Epub 2014 Oct 23.

Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan, ROC; Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC. Electronic address:

Objective: Women with atypical hyperplasia (AH) are often found to have endometrial carcinoma (EC) at hysterectomy. The purpose of this study was to evaluate whether the hypermethylation of specific genes found by methylomic approaches to the study of gynecologic cancers is a biomarker for EC in women with AH.

Methods: We evaluated the methylation of AJAP1, HS3ST2, SOX1, and PTGDR from 61 AH patients undergoing hysterectomy. Endometrial biopsy samples were analyzed by bisulfite conversion and quantitative methylation-specific polymerase chain reaction. A methylation index was used to predict the presence of cancer. To confirm the silencing effects of DNA methylation, immunohistochemical analysis of AJAP1, HS3ST2, and SOX1 was performed using tissue microarray.

Results: Fourteen (23%) patients had EC at hysterectomy. AJAP1, HS3ST2, and SOX1 were highly methylated in the EC patients' biopsy samples (p≤0.023). AJAP1, HS3ST2, and SOX1 protein expression was significantly higher in patients with AH only (p≤0.038). The predictive value of AJAP1, HS3ST2, and SOX1 methylation for EC was 0.81, 0.72, and 0.70, respectively. Combined testing of both AJAP1 and HS3ST2 methylation had a positive predictive value of 56%, methylation of any one of AJAP1, SOX1, or HS3ST2 had a 100% negative predictive value.

Conclusions: Hypermethylation of AJAP1, HS3ST2, and SOX1 is predictive of EC in AH patients. Testing for methylation of these genes in endometrial biopsy samples may be a hysterectomy-sparing diagnostic tool. Validation of these new genes as biomarkers for AH screening in a larger population-based study is warranted.
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http://dx.doi.org/10.1016/j.ygyno.2014.10.018DOI Listing
December 2014

Outcome of patients with bulky IB (≥ 6 cm) cervical squamous cell carcinoma with and without cisplatin-based neoadjuvant chemotherapy.

Taiwan J Obstet Gynecol 2014 Sep;53(3):330-6

Division of Gynecology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan. Electronic address:

Objective: To study the surgical morbidity and outcomes of patients with markedly bulky cervical squamous cell carcinoma (≥ 6 cm Cx-SCC) who underwent radical hysterectomy (RH) with and without neoadjuvant chemotherapy (NACT).

Materials And Methods: This retrospective study enrolled patients with International Federation of Gynecology and Obstetrics (FIGO) IB markedly bulky Cx-SCC who were treated with either three courses of weekly single agent cisplatin NACT (50 mg/m2) and subsequent radical hysterectomy (NACT-RH) or direct radical hysterectomy (RH) between 1996 and 2001. A total of 60 patients fulfilled the criteria, including 35 and 25 patients with NsACT-RH and RH, respectively.

Results: There was no statistically significant difference in basic characteristics between the two groups, except the smaller pathological tumor size, less blood loss, and lower immediate complication rate in the NACT-RH group. Median survival was 143.8 months in the NACT-RH group and 129.8 months in the RH group, respectively, without a statistically significant difference. Multivariate analysis showed that large pathological tumor size [hazard ratio (HR) 10.66, 95% confidence interval (CI) 2.93-38.80], the presence of para-aortic lymph node metastases and an immediate complication (HR 8.33 and 4.55, 95% CI 1.66-41.75 and 1.35-15.27, respectively) contributed to a worse outcome.

Conclusion: Weekly single agent cisplatin NACT indeed reduced the pathological tumor size and immediate complication rate during the RH, supporting the feasibility of subsequent RH in the management of patients with bulky Cx-SCC.
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http://dx.doi.org/10.1016/j.tjog.2014.05.001DOI Listing
September 2014

Correlation of ovarian fibroma with elevated serum CA-125.

Taiwan J Obstet Gynecol 2014 Mar;53(1):95-6

Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei, Taiwan; Taipei Medical University, Taipei, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.tjog.2012.12.005DOI Listing
March 2014

Serum cytokeratin-19 fragment (Cyfra 21-1) is a prognostic indicator for epithelial ovarian cancer.

Taiwan J Obstet Gynecol 2014 Mar;53(1):30-4

Department of Obstetrics and Gynecology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan. Electronic address:

Objectives: Cytokeratin 19 is significant for indicating cancer cells, and Cyfra 21-1 is a fragment of cytokeratin 19. This retrospective study was designed to define the prognostic value of serum Cyfra 21-1 in epithelial ovarian cancers (EOC).

Materials And Methods: Serum Cyfra 21-1 concentration was obtained from 42 patients with EOC prior to treatment. Various prognostic aspects were examined using univariable and multivariable analyses. The standard serum marker cancer antigen 125 was measured simultaneously and compared in this analysis.

Results: Serum levels of both Cyfra 21-1 and cancer antigen 125 were associated with positive retroperitoneal lymph nodes and platinum resistance; higher levels of Cyfra 21-1 (3.0 ng/mL as the cut-off) were associated with shorter disease-free survival (16 months vs. 28 months, p = 0.001) and overall survival (29 months vs. 41 months, p = 0.007) than lower levels. Further univariable analysis showed that Cyfra 21-1, poor differentiation, and retroperitoneal lymph node metastasis were related to platinum resistance and mortality. Multivariable analysis indicated retroperitoneal lymph node metastasis and serum Cyfra 21-1 were independent risk factors for both disease-free survival and overall survival.

Conclusion: The pretreatment level of serum Cyfra 21-1 had remarkable prognostic significance for EOC, indicating poor survival when it was elevated above 3.0 ng/mL.
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http://dx.doi.org/10.1016/j.tjog.2013.02.002DOI Listing
March 2014

Hormone therapy for patients with advanced or recurrent endometrial cancer.

J Chin Med Assoc 2014 May 30;77(5):221-6. Epub 2014 Mar 30.

Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Foundation of Gynecological Cancer, Taipei, Taiwan, ROC; Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC. Electronic address:

The "gold standard" treatment for endometrial cancer is completely staged surgery, followed by radiation or chemotherapy, based on the final pathological surgical stage and requirements. In the primary treatment of endometrial cancers, hormones are rarely taken into consideration after primary surgery. Primary treatment with hormones to preserve fertility in younger women with endometrial cancer is an attractive option, and many successful cases have been reported, although the majority of them finally received definite therapy, including total hysterectomy. The role of hormone therapy is often delayed in recurrent disease; response rates to progestins and tamoxifen or aromatase inhibitors in advanced/recurrent endometrial cancers are approximately 15-20% and nearly ≤ 10%, respectively. This review is focused on updated information and recent knowledge on the use of hormones in the management of women with advanced or recurrent endometrial cancers.
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http://dx.doi.org/10.1016/j.jcma.2014.02.007DOI Listing
May 2014

Suppression of migratory/invasive ability and induction of apoptosis in adenomyosis-derived mesenchymal stem cells by cyclooxygenase-2 inhibitors.

Fertil Steril 2010 Nov 12;94(6):1972-9, 1979.e1-4. Epub 2010 Mar 12.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Institute of Clinical Medicin, National Yang-Ming University, Taipei, Taiwan.

Objective: To investigate if stem or progenitor cells are found in adenomyosis and to characterize the role of cyclooxygenase-2 (COX-2) in adenomyosis-derived mesenchymal stem cell (AMSC)-related pathogenesis of adenomyosis.

Design: Experimental clinical study.

Setting: University hospital.

Patient(s): Ten patients with adenomyosis.

Intervention(s): Hysterectomy.

Main Outcome Measure(s): The gene expression of AMSCs and endometrial mesenchymal stem cells (EMSCs) were analyzed by microarray, quantitative polymerase chain reaction and Western blot. Methylthiazol tetrazolium, proliferation, apoptosis, and migration/invasion assays of AMSCs and EMSCs were evaluated after COX-2 inhibitor treatment.

Result(s): We isolated nine EMSCs from normal endometrium (n=10) and six AMSCs (n=10) from adenomyosis. The morphology, phenotype, and potential of multilineage differentiation between EMSCs and AMSCs were not significantly different. Using complementary DNA microarrays, the expression profiles of EMSCs are related to those of bone marrow-derived mesenchymal stem cells (BMSCs), but AMSCs are different from EMSCs and BMSCs in the gene profiles. We validated the microarray results and showed that there is increased COX-2 expression in AMSCs compared with EMSCs. Treatment with a COX-2 inhibitor suppressed migration and invasion and induced apoptotic capabilities of AMSCs, but not of EMSCs.

Conclusion(s): Overexpression of COX-2 in AMSCs may play an important role in the pathogenesis of adenomyosis. COX-2 could be a possible target for treatment and prevention of adenomyosis.
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http://dx.doi.org/10.1016/j.fertnstert.2010.01.070DOI Listing
November 2010

Physiology and potential application of NKT cells: a minireview.

Chin J Physiol 2009 Oct;52(5):275-9

Department of Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.

CD1d-restricted T (NKT) cells are potent regulators of autoimmunity, tumor immunity, and transplantation-related immunity. NKT cells are a subset of innate lymphocytes that recognize endogenous or exogenous glycolipids in the context of CD1d molecules. Recent progress in the research of NKT cells has proved that NKT cells function as a bridge between innate and adaptive immunity in anticancer immunity. Furthermore, NKT cells also function as a bridge to tolerance or rejection of grafts in organ transplantation. Harnessing the function of NKT cells, and trying to put it into clinical application in the treatment of autoimmune disease, anticancer cell immunotherapy, and organ transplantation are the dreams of immunologists. This minireview will focus on the physiology of NKT cells and potential clinical application.
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http://dx.doi.org/10.4077/cjp.2009.amh058DOI Listing
October 2009

Overexpression of Aurora B is associated with poor prognosis in epithelial ovarian cancer patients.

Virchows Arch 2009 Nov 17;455(5):431-40. Epub 2009 Oct 17.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.

Recent studies have indicated that Aurora B expression is related to cell proliferation and prognosis in many cancers, but its association with epithelial ovarian carcinoma is not fully understood. Therefore, we examined the Aurora B kinase expression in epithelial ovarian cancer patients. Using immunohistochemistry, the expression levels of Aurora B and phosphohistone H3 (Ser(10)) (mitosis-specific marker) were measured in 156 patients with epithelial ovarian cancer. The expression levels of Aurora B at the protein and messenger RNA levels were examined using Western blotting and reverse transcriptase polymerase chain reaction. In total, 53 tumorous ovarian samples (34.0%) showed Aurora B overexpression, which was significantly higher than that found in the 15 normal ovarian tissue samples (0%, p = 0.006). The overexpression of Aurora B was also significantly higher in cases showing phosphohistone H3 (Ser(10)) overexpression (44.3% vs. 27.4%, p = 0.03). In addition, the expression of Aurora B in poorly and moderately differentiated carcinomas of the ovary was significantly higher than in well-differentiated carcinomas (53.6% vs. 28.2% vs.10.0%, respectively, p = 0.02). The overexpression of Aurora B was significantly higher in cases with lymph node metastasis (p = 0.01) and a positive ascites cytology (p = 0.008). Overall, the Aurora B overexpression group demonstrated a significantly shorter progression-free survival (p = 0.001) and overall survival (p = 0.023) than the Aurora B low expression group using univariate analysis (log-rank statistic). Aurora B is an effective predictor of aggressive epithelial ovarian carcinoma in terms of differentiation, metastasis, and prognosis.
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http://dx.doi.org/10.1007/s00428-009-0838-3DOI Listing
November 2009

Expression of Aurora kinase A and B in normal and malignant cervical tissue: high Aurora A kinase expression in squamous cervical cancer.

Eur J Obstet Gynecol Reprod Biol 2009 Jan 6;142(1):57-63. Epub 2008 Dec 6.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.

Objective: Aurora kinases such as Aurora A and B are key regulators of mitosis and tumorigenesis and have been reported to be overexpressed in various malignancies. However, the expression of Aurora kinases in normal and neoplastic cervical tissues remains undetermined.

Study Design: Immunohistochemical expression of Aurora A and B kinase was examined in 20 normal cervix, 35 cervical intraepithelial neoplasm 3 (CIN 3) and 95 cervical cancers, including squamous cell carcinoma (SCC) (n=76) and adenocarcinoma (AC) (n=19). Expression of Aurora A and B kinase was confirmed by Western blot. The correlation between Aurora A and B kinases expression and the clinico-pathological parameters was analyzed by statistical analysis.

Results: The Aurora A and B expression was significantly increased in carcinoma and CIN 3, compared with normal cervix. However, expression of Aurora A and B showed no significant correlation between CIN 3 and cervical cancer. The nuclear expression of Aurora A showed a significantly positive correlation with the expression of Aurora B (P=0.018). The percentage of Aurora A overexpression between SCCs and ACs showed a significant difference (50% vs. 21.1%, P=0.023). However, there was no correlation of Aurora A and B expression with patient survival.

Conclusion: According to our study, Aurora A and B overexpression is a relatively early phenomenon in the genesis of malignant epithelial neoplasm tumorigenesis. Based on the results of this study, it would be interesting to know whether Aurora kinases play a role in pathogenesis of cervical dysplasia and SCC patients.
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http://dx.doi.org/10.1016/j.ejogrb.2008.09.012DOI Listing
January 2009

Symptomatic myoma treated with laparoscopic uterine vessel occlusion and subsequent immediate myomectomy: which is the optimal surgical approach?

Fertil Steril 2009 Aug 18;92(2):762-9. Epub 2008 Oct 18.

Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine and Taipei Veterans General Hospital, Taipei, Taiwan.

Objective: To determine the optimal surgical approach when patients are treated with laparoscopic uterine vessel occlusion (LUVO) combined with myomectomy in the management of women with symptomatic uterine fibroids.

Design: An observational study.

Setting: Medical centers.

Patient(s): One hundred thirty-one patients with symptomatic myomas underwent LUVO plus laparoscopic myomectomy (LM; LUVO+LM) (n = 49) or LUVO plus ultra-mini laparotomy UMLT-M (LUVO+UMLT-M) (n = 82).

Intervention(s): Myomectomy through laparoscopy or UMLT access.

Main Outcome Measure(s): The outcome was measured by comparing surgical techniques, and 3-year follow-up, including symptom control and reintervention (hysterectomy or myomectomy), in both groups.

Result(s): General characteristics of the patients were similar in both groups, except the number of myomas. Surgical techniques seemed to be easier in the LUVO+UMLT-M group than in LUVO+LM group, because of less operation time (56.1 +/- 16.9 minutes vs. 73.4 +/- 26.9 minutes; P=.009) and a higher success rate (100% vs. 91.8%; P=.018). There were no differences in the 3-year follow-up of the therapeutic outcomes of the LUVO+UMLT-M and LUVO+LM groups, with low reintervention rates (1.2% vs. 0) and good symptom control rates in both groups.

Conclusion(s): The LUVO+LM, either through laparoscopy or UMLT, was acceptable in the management of symptomatic uterine fibroids. However, the LUVO+UMLT-M technique might be more feasible, as it required less operative time and had a higher success rate.
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http://dx.doi.org/10.1016/j.fertnstert.2008.06.038DOI Listing
August 2009

Comparison of ultraminilaparotomy for myomectomy through midline vertical incision or modified Pfannenstiel incision--a prospective short-term follow-up.

Fertil Steril 2009 May 14;91(5):1945-50. Epub 2008 Apr 14.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan.

Objective: To evaluate the short-term therapeutic outcome of myomectomy using ultraminilaparotomy (UMLT) through a midline vertical incision (MVI) or a modified Pfannenstiel incision (MPI) in the treatment of myomas.

Design: Controlled, nonrandomized clinical study.

Setting: University-affiliated medical center.

Patient(s): Ninety-eight patients with symptomatic, uncomplicated myomas warranting myomectomy. Forty-three patients underwent UMLT myomectomy by MVI and 55 by MPI.

Intervention(s): UMLT myomectomy through MI or MPI access.

Main Outcome Measure(s): The outcome was measured by comparing incision length, blood loss, operative time, postoperative pain, complications, success rate, postoperative recovery, and the return to work capability in both groups.

Result(s): General characteristics of the patients were similar in both groups. There were no statistical differences in postoperative recovery, complications, and success rate between the two groups. However, the operative technique seemed to be easier and more acceptable in the MVI group compared with that in the MPI group, because of the smaller incision wound, less operation time, and less blood loss. By contrast, less postoperative pain and an earlier return to work capability were noted in the MPI group.

Conclusion(s): This study has demonstrated that UMLT myomectomy using either a MVI or MPI can be applied in the successful management of uncomplicated myomas. The MPI technique was more complicated, but yielded less wound pain and earlier postoperative recovery for the women during this 1-year short-term follow-up.
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http://dx.doi.org/10.1016/j.fertnstert.2008.02.134DOI Listing
May 2009

Postpartum sterilization: the choice of laparoscopy or minilaparotomy?

Eur J Obstet Gynecol Reprod Biol 2008 Jul 6;139(1):116-7; author reply 117-8. Epub 2008 Mar 6.

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http://dx.doi.org/10.1016/j.ejogrb.2008.01.012DOI Listing
July 2008

Laparoscopic surgery for early-stage endometrial cancers.

Gynecol Oncol 2008 Feb 26;108(2):456-7; author reply 457-8. Epub 2007 Nov 26.

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http://dx.doi.org/10.1016/j.ygyno.2007.10.020DOI Listing
February 2008

Regulatory T cells: potential target in anticancer immunotherapy.

Taiwan J Obstet Gynecol 2007 Sep;46(3):215-21

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Veterans General Hospital, Taipei, Taiwan.

The concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor alpha-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cell-mediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed.
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http://dx.doi.org/10.1016/S1028-4559(08)60023-6DOI Listing
September 2007

Positron emission tomography and uterine leiomyomas.

Gynecol Oncol 2007 Dec 10;107(3):593-4; author reply 594-5. Epub 2007 Sep 10.

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http://dx.doi.org/10.1016/j.ygyno.2007.08.005DOI Listing
December 2007

The power Doppler velocity index, pulsatility index, and resistive index can assist in making a differential diagnosis of primary ovarian carcinoma and Krukenberg tumors: a preliminary study.

J Ultrasound Med 2007 Jul;26(7):921-6; quiz 927-9

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.

Objective: The aim of this study was to compare the effectiveness of transvaginal power Doppler sonography with spectral Doppler analysis as an aid in preoperatively distinguishing primary ovarian carcinoma and metastatic carcinoma to the ovary (Krukenberg tumors).

Methods: Fifty women with ovarian disease were preoperatively examined with transvaginal power Doppler sonography. Six basic parameters were measured, including intratumoral peak systolic velocity, end-diastolic velocity, time-averaged maximum velocity, pulsatility index (PI), resistive index (RI), and velocity index (VeI). Blood flow analyses were detectable in all patients. Twelve patients with metastatic carcinoma to the ovary were classified as group 1; 38 patients with primary ovarian carcinoma were classified as group 2. Comparison of intratumoral blood flow analyses between the two groups was performed.

Results: The PI, RI, and VeI were significantly lower in patients with metastatic carcinoma to the ovary than those with primary ovarian carcinoma (P < .05). There were no significant differences in the peak systolic velocity (P = .871), end-diastolic velocity (P = .508), and time-averaged maximum velocity (P = .850) between the two groups.

Conclusions: Transvaginal power Doppler sonography with spectral Doppler analysis is an effective method in evaluating intratumoral blood flow of Krukenberg tumors. Low impedance (PI, RI, and VeI) might assist us in making differential diagnoses between primary ovarian carcinoma and Krukenberg tumors according to our preliminary results.
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http://dx.doi.org/10.7863/jum.2007.26.7.921DOI Listing
July 2007

Effect of a selective nonsteroidal anti-inflammatory drug, celecoxib, on the reproductive function of female mice.

J Chin Med Assoc 2007 Jun;70(6):245-8

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan, R.O.C.

Background: The aim of the present study was to determine if long-term use of a cyclooxygenase-2 (COX-2) inhibitor affects fertility or ovulation in female mice.

Methods: Twenty-four female mice, 25 days of age, were given a selective COX-2 inhibitor: 3 mg/kg celecoxib (n = 8), 5 mg/kg celecoxib (n = 8),or placebo (n = 8) in a random fashion. Eight female mice, 10-11 weeks old, given 3 mg/kg celecoxib (n = 4) or placebo (n = 4) were subjected to continuous mating studies.

Results: Results from the 24 mice (n = 8 for each group) showed that oocyte number was not significantly different between female mice treated with either 3 mg/kg or 5 mg/kg celecoxib and placebo (21.4 +/- 2.5, 21.5 +/- 3.3, 23.3 +/- 3.8, respectively). From the continuous mating study, the litter size of female mice treated with celecoxib was not significantly different (8.2 +/- 1.3 pups/litter) compared to those treated with placebo (8.3 +/- 1.2 pups/litter). In addition, female mice treated with celecoxib had an average of 2.8 +/- 0.5 litters in a 12-week period, which was similar to female mice treated with placebo (3.0 +/- 0.8 litters/female).

Conclusion: This study suggests that use of low-dose (
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http://dx.doi.org/10.1016/S1726-4901(09)70367-3DOI Listing
June 2007

Successful rescue of an early interstitial pregnancy after failed systemic methotrexate treatment: a case report.

J Reprod Med 2007 Apr;52(4):332-4

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan.

Background: Interstitial (cornual) pregnancy is a rare and life-threatening disease. Although systemic treatment with methotrexate (MTX) in an unruptured interstitial pregnancy has been used to preserve the entirety of the uterus, surgery is often used as a rescue method in failed cases. Use of an ultrasound-guided local injection can be a good alternative to surgery.

Case: A 30-year-old woman, gravida 1, para 0, with an interstitial pregnancy at 10 weeks of gestation, was successfully treated with an ultrasound-guided 100-mg MTX injection after a failed response to 3-dose intramuscular 100-mg MTX treatment (300 mg in total). Regular menstruation occurred 1 month after the local MTX injection. The serum beta-human chorionic gonadotropin level was undetectable 49 days later, and the residual mass had disappeared 6 months later,

Conclusion: Local injection of MTX may be a good means of managing an unruptured interstitial pregnancy to preserve the entirety of the uterus after failed systemic MTX treatment. Use of a local MTX injection may be a better choice than that of systemic MTX treatment.
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April 2007

Alpha 2,6-sialyltransferase I expression in the placenta of patients with preeclampsia.

J Chin Med Assoc 2007 Apr;70(4):152-8

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.

Background: The expression of sialyl-glycoconjugates changes during development, differentiation and oncogenic transformation, tumor invasion and metastasis. Similarly, in the early stage of pregnancy, trophoblast cells have to undergo adhesion, invasion, and proliferation to develop a healthy placenta; the cytobiologic behavior is similar to tumor growth and invasion. Inadequate trophoblast invasion to the spiral artery in the 2nd trimester of pregnancy was believed to be correlated with pregnancy complications, including preeclampsia.

Methods: Alterations in alpha2,6-sialyltransferase I (ST6Gal I) mRNA in the placental tissues of women with preeclampsia (n=20) and without preeclampsia (n=20 used as a control) were examined by semiquantitative reverse transcription-polymerase chain reaction and real-time quantitative reverse transcription-polymerase chain reaction. The transcription regulators of ST6Gal I including a "constitutive" promoter (Y + Z form), "hepatic" promoter (H form), and lymphoblastic promoter (X form) were investigated. The enzyme activity of ST6Gal I was also examined.

Results: Both mRNA expression and enzyme activity of ST6Gal I did not show a significant difference in the placental tissues of the women of both groups. The transcription regulators of ST6Gal I, including the Y+Z form and the H form, also failed to show any difference. The X form, seldom detected in the study, was excluded from analysis.

Conclusion: Our results suggested that ST6Gal I was not involved in the pathogenesis of the preeclampsia.
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http://dx.doi.org/10.1016/S1726-4901(09)70349-1DOI Listing
April 2007

Postconization cervical perforation during laparoscopic surgery.

Taiwan J Obstet Gynecol 2007 Mar;46(1):71-2

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, Taipei, Taiwan.

Objective: Complications during laparoscopic surgery involving the bladder, bowel, and major vessels have been reported extensively. However, uterine manipulator-associated injuries are seldom reported.

Case Report: We describe herein the case of a 28-year-old female patient who underwent a laparoscopic cystectomy 5 days after cervical conization, during which the uterine manipulator perforated the anterior cul-de-sac through the cervix. Fortunately, the wound healed with conservative treatment and no adverse consequences were found.

Conclusion: This case serves to highlight the potential for complications following seemingly benign maneuvers.
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http://dx.doi.org/10.1016/S1028-4559(08)60112-6DOI Listing
March 2007

A simple method to accurately position Port-A-Cath without the aid of intraoperative fluoroscopy or other localizing devices.

J Surg Oncol 2007 Jun;95(7):582-6

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan.

Background: To evaluate the efficacy and acceptability of the Port-A-Cath (PAC) insertion method with (conventional group as II) and without (modified group as I) the aid of intraoperative fluoroscopy or other localizing devices.

Methods: A total of 158 women with various kinds of gynecological cancers warranting PAC insertion (n = 86 in group I and n = 72 in group II, respectively) were evaluated. Data for analyses included patient age, main disease, dislocation site, surgical time, complications, and catheter outcome.

Results: There was no statistical difference between the two groups in terms of age, main disease, complications, and the experiencing of patent catheters. However, appropriate positioning (100% in group I, and 82% in group II) in the superior vena cava (SVC) showed statistical differences between the two groups (P = 0.001). In addition, the surgical time in group I was statistically shorter than that in group II (P < 0.001).

Conclusions: The modified method for inserting the PAC offered the following benefits: including avoiding X-ray exposure for both the operator and the patient, defining the appropriate position in the SVC, and less surgical time.
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http://dx.doi.org/10.1002/jso.20754DOI Listing
June 2007

Natural progression of menstrual pain in nulliparous women at reproductive age: an observational study.

J Chin Med Assoc 2006 Oct;69(10):484-8

Division of General Gynecology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.

Background: Menstrual pain can be alleviated after childbirth. The purpose of this observational study was to evaluate the natural progression of menstrual pain among nulliparous women at their reproductive age.

Methods: A questionnaire-based study of perimenopausal women with a history of primary dysmenorrhea was performed. The study subjects were recruited between July 1, 2001 and June 30, 2005. Severity of menstrual pain was graded using a multidimensional scoring system.

Results: A total of 247 nulliparous women with primary dysmenorrhea were enrolled, and of these, 218 patients were eligible for analysis. Patients who had more frequent intercourse (p = 0.016), fewer associated systemic symptoms (p = 0.028), and use of oral contraceptive pills (p = 0.039) tended to have a higher chance of an improvement in dysmenorrhea after age 40. Multidimensional scoring distribution over chronologic age revealed that patients had significantly improved menstrual pain after 40 years of age.

Conclusion: For nulliparous women with primary dysmenorrhea, the severity of menstrual pain decreased significantly after age 40. More studies are needed to explore this phenomenon from a biochemical or molecular basis.
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http://dx.doi.org/10.1016/S1726-4901(09)70313-2DOI Listing
October 2006

Single-dose sertaconazole vaginal tablet treatment of vulvovaginal candidiasis.

J Chin Med Assoc 2006 Jun;69(6):259-63

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan, ROC.

Background: Vulvovaginal candidiasis (WC) is a bothersome disease in women. Poor compliance with the continuous use of antifungal vaginal drugs often results in treatment failure. The aim of the present study was to evaluate the efficacy, acceptability, and safety of single-dose sertaconazole vaginal tablet (500 mg) treatment compared with conventional 3-dose econazole vaginal tablet (150 mg) treatment for VVC.

Methods: In this open, randomized, and comparative study, 40 symptomatic patients with VVC confirmed by the smear method were enrolled. Patients in group A were treated with single-dose sertaconazole vaginal tablet and those in group B were treated continuously with econazole vaginal tablet for 3 days.

Results: The characteristics of the patients in both groups were comparable and without statistical difference. Group A showed a significantly better clearance rate for candidiasis than group B (100% vs. 72.2% on day 7, p = 0.013; 100% vs. 77.8% on day 14, p = 0.030), based on smear method results. Group A showed a more rapid response for symptom relief than group B on day 7, but there was no difference in overall symptom relief between group A and group B on day 14.

Conclusion: Single-dose sertaconazole proved to be a more convenient and symptom-relieving treatment for VVC. The advantages of such management are worthy of further study in women with relapse VVC.
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http://dx.doi.org/10.1016/S1726-4901(09)70253-9DOI Listing
June 2006
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