Wen-Shiung Liou

VGHKS Kaohsiung Veterans General Hospital, Kao-hsiung-shih, Kaohsiung, Taiwan

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Publications (19)36.28 Total impact

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    ABSTRACT: Accumulating studies in tumorigenesis indicate that dysregulated gene expression caused by genetic and epigenetic changes lead to the formation of human cancers, and most dysregulated or dysfunctional genes are associated with cell proliferation, programmed cell death (PCD), metastasis, and, in part, tumor suppressor genes (TSGs) or oncogenes. Epigenetic modifications are important regulatory mechanisms that are induced by chemical treatment or environmental changes. Recently, studies have considered the effects of epigenetic modifications on tumorigenesis and disease. Over the past few decades, dietary polyphenols have become a focus of investigation because of their bioactive function in cancer prevention and treatment. In this review article, we summarize the current research on the anti-cancer effects of polyphenols and provide useful information to help promote polyphenol application in cancer research.
    No preview · Article · Jan 2016
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    ABSTRACT: Obesity is caused by excessive accumulation of body fat and is closely related to complex metabolic diseases. Adipogenesis is a key process that is required in adipocyte hypertrophy in the development of obesity. Curcumin (Cur) has been reported to inhibit adipocyte differentiation, but the inhibitory effects of other curcuminoids present in turmeric, such as demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), on adipogenesis have not been investigated. Here, we investigated the effects of curcuminoids on adipogenesis and the molecular mechanisms of adipocyte differentiation. Among three curcuminoids, BDMC was the most effective suppressor of lipid accumulation in adipocytes. BDMC suppressed adipogenesis in the early stage primarily through attenuation of mitotic clonal expansion (MCE). In BDMC-treated preadipocytes, cell cycle arrest at the G0/G1 phase was found after initiation of adipogenesis and was accompanied with downregulation of cyclin A, cyclin B, p21 and mitogen-activated protein kinase (MAPK) signaling. The protein levels of the adipogenic transcription factors PPARγ and C/EBPα were also reduced by BDMC treatment. Furthermore, 0.5% dietary BDMC (w/w) significantly lowered body weight gain and adipose tissue mass in high-fat diet (HFD)-fed mice. The results of H&E staining showed that dietary BDMC reduced hypertrophy in adipocytes. These results demonstrate for the first time that BDMC suppressed adipogenesis in 3T3-L1 adipocytes and prevented HFD-induced obesity. Our results suggest that BDMC has the potential to prevent obesity.
    No preview · Article · Jan 2016 · Journal of Agricultural and Food Chemistry
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    ABSTRACT: Objective: The goal of this study was to investigate the impact of ovarian preservation on the survival of women with early-stage endometrial cancer, particularly young women. Materials and methods: A study cohort of 64 patients with histologically confirmed early-stage endometrial cancer was retrospectively collected from 10 member hospitals of the Taiwanese Gynecologic Oncology Group between 1998 and 2009. Survivorship and overall survival were compared between these two groups using a log-rank test. Results: All patients who underwent surgery were adult women with a mean age of 40.4 ± 9.2 years (range 24-63 years). Ovary-preserving surgery was performed in 38 (59.4%) patients who desired to preserve their ovaries, incidentally in 19 (29.7%) patients with a preoperative diagnosis other than endometrial carcinoma, and in seven patients (10.9%) with unknown reasons. The 5-year recurrence-free survival rate was 98.3% with a median follow up of 44.6 months (range 1.0-126.9 months). Eight patients required adjuvant treatment (12.5%); one patient had documented local recurrence (1.6%); and no metachronous ovarian malignancy occurred during follow up. Conclusion: Preservation of bilateral ovaries does not increase cancer-related mortality. A more conservative approach to surgical staging may be considered in premenopausal women with early-stage endometrial cancer without risk factors.
    No preview · Article · Oct 2015 · Taiwanese Journal of Obstetrics and Gynecology

  • No preview · Article · Sep 2015 · Taiwanese journal of obstetrics & gynecology
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    ABSTRACT: Invasive procedures including loop electrosurgical excision, cervical conization, and endometrial sampling are often recommended when atypical glandular cells (AGC) are detected on Pap smear with unsatisfactory colposcopy. These invasive procedures may result in patient anxiety, increased medical expense, and increasing the risk of preterm delivery in subsequent pregnancies. This study was performed to assess methylation biomarkers in the triage of AGC on Pap smear for invasive procedures. We conducted a multicenter study in 13 medical centers in Taiwan from May 2012 to May 2014. A total of 55 samples diagnosed "AGC not otherwise specified" (AGC-NOS) were included. All patients with AGC underwent colposcopy, cervical biopsy, endometrial sampling, and conization if indicated. Multiplex quantitative methylation-specific polymerase chain reaction (QMSPCR) was performed. Sensitivity, specificity, and accuracy were calculated for detecting CIN3+ and endometrial complex hyperplasia. In 55 patients with AGC, the sensitivity for methylated (m) SOX1m, PAX1 m, ZNF582m,PTPRRm, AJAP1m, HS3ST2m, and POU4F3m for detecting CIN3+ and endometrial complex hyperplasia lesions was 100, 86, 71, 86, 86, 57, and 100%; specificity was 67, 79, 85, 50, 52, 96, and 52%, respectively. Testing for high risk-HPV had a sensitivity of 57% and specificity of 75% for CIN3+ and endometrial complex hyperplasia lesions. Methylated (m) SOX1m and POU4F3m could be new methylation biomarkers for detection of CIN3+ and endometrial complex hyperplasia in AGC. Women with AGC and positive SOX1m / POU4F3m, colposcopy, cervical conization or endometrial sampling should be considered.
    Full-text · Article · Jun 2015 · PLoS ONE
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    ABSTRACT: The aim of this study is to evaluate the long-term outcome of ovarian recurrent granulosa cell tumors (GCTs) in a large series of patients treated in Taiwanese Gynecologic Oncology Group (TGOG) centers and to define the prognostic parameters for survival. A retrospective multi-institutional review of patients with recurrent ovarian GCTs treated in TGOG centers was conducted. The clinical and pathological characteristics, treatment, and outcomes of patients with ovarian recurrent GCTs were analyzed using Kaplan-Meier and Cox proportional hazards analyses to determine the predictors for survival. A total of 44 patients from 16 medical centers were identified between January 1994 and December 2010. The median disease-free survival (DFS), postrecurrence survival, and overall survival (OS) were 61.5 months (range, 3.7-219.3 months), 55.8 months (range, 4.6-193.7 months), and 115.3 months (range, 17.2-390.6 months), respectively. In multivariate analysis, DFS (> 61.5 months versus ≤ 61.5 months, hazard ratio (HR) 0.15, 95% confidence interval (CI) 0.03-0.78, p = 0.024) at the initial operation after diagnosis of relapse was the only predictor that correlated with OS. DFS after the initial operation was the only important predictor for overall survival in patients with recurrent GCTs, regardless of treatment, suggesting that the natural behavior of the tumor is a critical factor for patients with recurrent GCTs. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jun 2015 · Taiwanese journal of obstetrics & gynecology
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    ABSTRACT: Silibinin is known to display high efficacy against cancer cells and for hepatic protection. Metformin, a well-known antidiabetic agent, has recently been reported to inhibit cancer. In the present study, we investigated the effect of metformin on silibinin-induced programmed cell death in cervical cancer cells (C-33A). MTT assay and Western blot assays were performed to quantify cell viability and the expression of signaling proteins, respectively. Combined treatment with metformin and silibinin decreased cell survival in synergistic manner in C-33A cells at a dose that did not affect nonmalignant cells (HUVECs). Silibinin and metformin increased PTEN and AMPK expression in C-33A cells, respectively. Combined treatment caused a greater increase in the expression of activated caspase-3 or AIF, indicating apoptosis. Combined treatment with silibinin and metformin may induce programmed cell death of human cervical cancer cells at a dose that does not affect HUVECs. This finding reveals a potential therapeutic strategy of cervical cancer.
    No preview · Article · May 2015 · Journal of applied biomedicine
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    ABSTRACT: A recent randomized trial demonstrated that concurrent chemoradiotherapy (CCRT) with weekly cisplatin and gemcitabine, followed by two adjuvant cycles of cisplatin and gemcitabine improved survival for advanced cervical cancer patients. An Asian Gynecologic Oncology Group (AGOG) study was designed to determine whether only adding gemcitabine in the chemoradiation phase without adjuvant chemotherapy could improve survival. Between March 2009 and March 2013, 74 eligible patients with International Federation of Obstetrics and Gynecology stage III/IVA cervical cancer or stage I/II with positive pelvic/para-aortic nodal metastasis were enrolled. Thirty-seven patients were randomized to arm C (weekly cisplatin 40 mg/m(2)) and 37 patients were randomized to arm CG (weekly cisplatin 40 mg/m(2) and gemcitabine 125 mg/m(2)), for six cycles. Six eligible patients were excluded before the beginning of treatment. An interim analysis showed superimposable progression-free (PFS) and overall survival (OS), a decision of closing accrual was made. 3-year PFS was similar in both arms (arm C 65.1% vs arm CG 71.0%, p = 0.71), and 3-year OS was 74.1% in arm C vs 85.9% in arm CG (p = 0.89), but crossed over at 5 years. Grade 2-4 hematological toxicities, including neutropenia (p = 0.028) and thrombocytopenia (p = 0.001), were more frequent in arm CG than arm C. Despite limitation in power, it suggests that only adding gemcitabine at the CCRT phase does not provide substantially superior results, but treatment toxicities could increase. Further studies are required to determine the role of post-CCRT adjuvant chemotherapy in advanced cervical cancer. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Mar 2015 · Gynecologic Oncology
  • Fu-Nan Cho · Cheng-Bin Liu · James R. Carey · Wen-Shiung Liou

    No preview · Article · Sep 2014 · Taiwanese Journal of Obstetrics and Gynecology
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    ABSTRACT: This study aimed to determine the clinical prognostic factors involved in carcinosarcoma of the ovary, fallopian tube, and peritoneum. This retrospective study was undertaken by the Taiwanese Gynecologic Oncology Group. The retrieved clinical data included demographic characteristics, medical disease, tumor status, extent of surgery, and adjuvant chemotherapy. In total, 63 patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum were identified. Sixty-one patients with complete data were enrolled for further data analysis. The mean follow-up period was 1.0 year, and the mean overall survival was 15.4 months. By log-rank tests, age, menopausal status, parity, hypertension, diabetes, primary tumor size, para-aortic lymph node metastasis, pretreatment CA-125, preceding diagnostic surgery, hysterectomy, lymphadenectomy, other surgeries, and paclitaxel use were not predictive of overall survival.Omentectomy, no gross residual implants after surgery, platinum treatment, and no pelvic lymph node metastasis had a trend toward better survival. Early diagnosis at stage I and cisplatin/ifosfamide regimen were significant associated with a better overall survival in log-rank and simple Cox regression tests. Bilateral ovarian tumors and metastatic tumors larger than 2 cm were significantly associated with a poorer overall survival. Early diagnosis at stage I, unilateral ovarian tumor, metastatic tumors less than 2 cm, and cisplatin/ifosfamide regimen were predictive of a better survival.Omentectomy and complete debulking surgery also showed a trend toward better survival. Thus, these treatment strategies should be applied in patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum.
    No preview · Article · Mar 2014 · International Journal of Gynecological Cancer
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    ABSTRACT: MicroRNAs (miRNAs, miRs) are a cluster of naturally occurring small non-coding RNA molecules of 19-24 nucleotides in length. miRs control gene expression post-transcriptionally by binding to a specific site at the 3'-UTR of target mRNA, which results in mRNA cleavage and translation repression. Nearly 1000 miRs in the human genome have been identified, and it is believed that these miRs contribute to at least 60% of the human transcriptome. Recent research has shown that miRs are emerging as important regulators of cellular differentiation and dedifferentiation. In addition, dysregulation of miR expression may play a fundamental role in the onset, progression and dissemination of cancers. In this review, we focus on some paradigms of miR involvement in tumorigenesis, such as ovarian cancer, and also discuss the relationship between miRs and cancer stem cells.
    Full-text · Article · Dec 2013 · Taiwanese journal of obstetrics & gynecology
  • Fu-Nan Cho · Cheng-Bin Liu · Ju-Yueh Li · James R Carey · Wen-Shiung Liou

    No preview · Article · Sep 2013 · Taiwanese journal of obstetrics & gynecology
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    ABSTRACT: Pterostilbene, found in grapes and berries, exhibits pleiotropic effects, including anti-inflammatory, antioxidant, and anti-proliferative activities. This study was conducted to investigate the effect of pterostilbene on liver fibrosis and the potential underlying mechanism for such effect. Sprague-Dawley rats were intraperitoneally given dimethyl n-nitrosamine (DMN) (10mg/kg) 3days per week for 4weeks. Pterostilbene (10 or 20mg/kg) was administered by oral gavage daily. Liver function, morphology, histochemistry, and fibrotic parameters were examined. Pterostilbene supplementation alleviated the DMN-induced changes in the serum levels of alanine transaminase and aspartate transaminase (p<0.05). Fibrotic status and the activation of hepatic stellate cells were improved upon pterostilbene supplementation as evidenced by histopathological examination as well as the expression of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and matrix metalloproteinase 2 (MMP2). These data demonstrated that pterostilbene exhibited hepatoprotective effects on experimental fibrosis, potentially by inhibiting the TGF-β1/Smad signaling.
    No preview · Article · Jun 2013 · Food Chemistry
  • Fu-Nan Cho · Cheng-Bin Liu · Ju-Yueh Li · San-Nung Chen · Wen-Shiung Liou

    No preview · Article · Mar 2013 · Taiwanese journal of obstetrics & gynecology

  • No preview · Article · Mar 2013 · Taiwanese journal of obstetrics & gynecology
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    ABSTRACT: Because of rarity, indolent clinical course, and of most importance, small sample size studies of previous ovarian granulosa cell tumors (GCTs), this study was conducted to report the clinical characteristics and long-term outcomes of 176 pathologically confirmed GCTs. Between 1984 and 2010, we retrospectively evaluated 176 patients from multiple medical centers in Taiwan. The mean age at the diagnosis was 46 years and nearly half of the patients (45.7%) were in their fourth or fifth decades of life. The most common symptoms included abdominal pain (28.5%), followed by irregular menstruation (16.7%). The mean tumor size was 10.4 cm. The stage distribution at diagnosis was stage I in 77.8% of patients, stage II in 5.1%, stages III-V in 6.1%, and unknown in 11% of patients. The median follow-up period was 60.7 months. The recurrence rate was 21%. The overall 5- and 10-year survival rates were 96.5% and 94.1%, respectively. In univariate analysis, initial stage, presence of residual tumor after initial surgery, need for adjuvant chemotherapy, and tumor size were associated with disease recurrence. In the multivariate analysis, only the presence of residual tumor after initial surgery and tumor size were significantly associated with recurrence. The outcomes of patients with GCTs were good, with nearly to 95% of patients surviving 5 and 10 years. The prognosis was related to initial stage, presence of residual tumor after initial surgery, and tumor size (>13.5 cm). Different surgical methods and/or adjuvant therapy appear not to affect the outcome.
    No preview · Article · Feb 2012 · Gynecologic Oncology
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    ABSTRACT: Our aims were to investigate the treatment and clinicopathological variables in relation to prognosis in small cell neuroendocrine cervical carcinoma (SCNECC). Clinical data of SCNECC patients with International Federation of Gynaecology and Obstetrics (FIGO) stages I-IV treated between 1987 and 2009 at member hospitals of the Taiwanese Gynecologic Oncology Group (TGOG) were retrospectively reviewed. Of the 179 eligible patients, 104 were of FIGO stage I, 19 stage IIA, 23 stage IIB, 9 stage III, and 24 stage IV. The median failure-free survival (FFS) was 16.0 months, and the median cancer-specific survival (CSS) was 24.8 months. In multivariate analysis, FIGO stage and lymph node metastasis were selected as independent variables in stages I-IV. In stages IIB-IVB, primary treatment containing etoposide and platinum for at least 5 cycles (EP5+) (n=16) was associated with significantly better 5-year FFS (42.9% versus 11.8%, p=0.041) and CSS (45.6% versus 17.1%, p=0.035) compared to other treatments (n=40). Furthermore, concurrent chemoradiation with EP5+ (CCRT-EP5+) was associated with even better 5-year FFS (62.5% versus 13.1%, p=0.025) and CSS (75.0% versus 16.9%, p=0.016). FIGO stage and lymph node metastasis are significant prognostic factors in SCNECC. In stages IIB-IVB, CCRT-EP5+ might be the treatment of choice, which could be also true for earlier stages. Despite limitations of a retrospective study spanning a long time period and heterogeneous managements, the results provide an important basis for designing future prospective studies.
    No preview · Article · Jan 2012 · European journal of cancer (Oxford, England: 1990)
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    ABSTRACT: Malignant melanoma of the vagina, a very rare malignancy, has a notoriously aggressive behavior associated with a high risk of local recurrence and distant metastasis. At present, there are various treatment options for this disease but no standard guideline. We describe a case of a 54-year-old woman with a locally advanced melanoma of the vagina, who underwent radical surgery, biochemotherapy with interferon-α-2b, chemotherapy, radiotherapy, and repeat excision of local recurrent lesions and brain metastasis. In conclusion, malignant melanoma of the vagina has a high risk for local recurrence. Repeated local excision followed by biochemotherapy is a tolerable treatment.
    Full-text · Article · Aug 2011 · Journal of the Chinese Medical Association
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    ABSTRACT: Serum CA-125 has been shown to be a sensitive tumor marker of recurrent ovarian cancer. The goal of this study was to evaluate the use of 2-[F-18]fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the early detection of recurrent ovarian cancer in patients with low-level increases in serum CA-125 levels. Patients who demonstrated a normalization of serum CA-125 levels after complete remission of ovarian cancer were recruited for this study. FDG-PET/CT was performed to evaluate serum CA-125 levels ≥ 35 U/mL (Group 1) or progressive low-level increases in the levels of serum CA-125 (Group 2). The results were analyzed based on pathology, disease progression, and/or clinical follow-up. Twenty-seven (27) consecutive patients consented to the aforementioned criteria (n = 16 in Group 1 and n = 11 in Group 2). In Group 1, of the 16 patients, 15 had a proven tumor recurrence, and the remaining 1 had a second primary cancer with no evidence of recurrent ovarian lesions. In Group 2, all 11 patients had recurrent tumors. The use of FDG-PET/CT allowed the detection of recurrences in 25 patients and a second primary cancer in 1 patient, which included all of the patients in Group 1 and 10 of the 11 patients in Group 2. The detection rate of FDG-PET/CT for recurrent ovarian cancer was 100% in Group 1 and 90.9% in Group 2 (15/15 vs. 10/11, p = 0.423). FDG-PET/CT changed the intended management in 14 (53.8%) of the patients, which included 4 cases in Group 1 and 10 cases in Group 2. FDG-PET/CT has the ability to detect recurrent ovarian cancer and second primary tumors in patients with increased levels of serum CA-125. FDG-PET/CT affects the clinical management by localizing recurrent lesions and creating a specific treatment plan for each patient, especially patients who demonstrate a low-level increase in serum CA-125 levels.
    No preview · Article · Apr 2011 · Cancer Biotherapy & Radiopharmaceuticals

Publication Stats

87 Citations
36.28 Total Impact Points


  • 2011-2016
    • VGHKS Kaohsiung Veterans General Hospital
      • Department of Obstetrics and Gynaecology
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2013
    • National Yang Ming University
      • Department of Obstetrics and Gynecology
      T’ai-pei, Taipei, Taiwan