Publications by authors named "Soon-Cen Huang"

34 Publications

COL11A1 activates cancer-associated fibroblasts by modulating TGF-β3 through the NF-κB/IGFBP2 axis in ovarian cancer cells.

Oncogene 2021 Jul 11;40(26):4503-4519. Epub 2021 Jun 11.

Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Ovarian cancer has a unique tumor microenvironment (TME) that enables cancer-associated fibroblasts (CAFs) to interact with cellular and matrix constituents and influence tumor development and migration into the peritoneal cavity. Collagen type XI alpha 1 (COL11A1) is overexpressed in CAFs; therefore this study examines its role during CAF activation in epithelial ovarian cancer (EOC). Coculturing human ovarian fibroblasts (HOFs) with high COL11A1-expressing EOC cells or exposure to the conditioned medium of these cells prompted the expression of COL11A1 and CAF phenotypes. Conversely, coculturing HOFs with low COL11A1-expressing EOC cells or COL11A1-knockdown abrogated COL11A1 overexpression and secretion, in addition to CAF activation. Increased p-SP1 expression attributed to COL11A1-mediated extracellular signal-regulated kinase activation (ERK) induced p65 translocation into the nucleus and augmented its binding to the insulin-like growth factor binding protein 2 (IGFBP2) promoter, ultimately inducing TGF-β3 activation. The CAF-cancer cell crosstalk triggered interleukin-6 release, which in turn promoted EOC cell proliferation and invasiveness. These in vitro results were confirmed by in vivo findings in a mouse model, showing that COL11A1 overexpression in EOC cells promoted tumor formation and CAF activation, which was inhibited by TGF-β3 antibody. Human tumors with high TGF-β3 levels showed elevated expression of COL11A1 and IGFBP2, which was associated with poor survival. Our findings suggest the possibility that anti-TGF-β3 treatment strategy may be effective in targeting CAFs in COL11A1-positive ovarian tumors.
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http://dx.doi.org/10.1038/s41388-021-01865-8DOI Listing
July 2021

Chemoresistant ovarian cancer enhances its migration abilities by increasing store-operated Ca entry-mediated turnover of focal adhesions.

J Biomed Sci 2020 Feb 21;27(1):36. Epub 2020 Feb 21.

Department of Biomedical Engineering, National Cheng Kung University, Tainan, 701, Taiwan.

Background: Among gynecological cancers, ovarian carcinoma has the highest mortality rate, and chemoresistance is highly prevalent in this cancer. Therefore, novel strategies are required to improve its poor prognosis. Formation and disassembly of focal adhesions are regulated dynamically during cell migration, which plays an essential role in cancer metastasis. Metastasis is intricately linked with resistance to chemotherapy, but the molecular basis for this link is unknown.

Methods: Transwell migration and wound healing migration assays were used to analyze the migration ability of ovarian cancer cells. Real-time recordings by total internal reflection fluorescence microscope (TIRFM) were performed to assess the turnover of focal adhesions with fluorescence protein-tagged focal adhesion molecules. SOCE inhibitors were used to verify the effects of SOCE on focal adhesion dynamics, cell migration, and chemoresistance in chemoresistant cells.

Results: We found that mesenchymal-like chemoresistant IGROV1 ovarian cancer cells have higher migration properties because of their rapid regulation of focal adhesion dynamics through FAK, paxillin, vinculin, and talin. Focal adhesions in chemoresistant cells, they were smaller and exhibited strong adhesive force, which caused the cells to migrate rapidly. Store-operated Ca entry (SOCE) regulates focal adhesion turnover, and cell polarization and migration. Herein, we compared SOCE upregulation in chemoresistant ovarian cancer cells to its parental cells. SOCE inhibitors attenuated the assembly and disassembly of focal adhesions significantly. Results of wound healing and transwell assays revealed that SOCE inhibitors decreased chemoresistant cell migration. Additionally, SOCE inhibitors combined with chemotherapeutic drugs could reverse ovarian cancer drug resistance.

Conclusion: Our findings describe the role of SOCE in chemoresistance-mediated focal adhesion turnover, cell migration, and viability. Consequently, SOCE might be a promising therapeutic target in epithelial ovarian cancer.
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http://dx.doi.org/10.1186/s12929-020-00630-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033940PMC
February 2020

Bcl2 regulates store-operated Ca entry to modulate ER stress-induced apoptosis.

Cell Death Discov 2018 Dec 26;4:37. Epub 2018 Feb 26.

2Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, 701 Taiwan.

Ca plays a significant role in linking the induction of apoptosis. The key anti-apoptotic protein, Bcl-2, has been reported to regulate the movement of Ca across the ER membrane, but the exact effect of Bcl-2 on Ca levels remains controversial. Store-operated Ca entry (SOCE), a major mode of Ca uptake in non-excitable cells, is activated by depletion of Ca in the ER. Depletion of Ca in the ER causes translocation of the SOC channel activator, STIM1, to the plasma membrane. Thereafter, STIM1 binds to Orai1 or/and TRPC1 channels, forcing them to open and thereby allow Ca entry. In addition, several anti-cancer drugs have been reported to induce apoptosis of cancer cells via the SOCE pathway. However, the detailed mechanism underlying the regulation of SOCE by Bcl-2 is not well understood. In this study, a three-amino acid mutation within the Bcl-2 BH1 domain was generated to verify the role of Bcl-2 in Ca handling during ER stress. The subcellular localization of the Bcl-2 mutant (mt) is similar to that in the wild-type Bcl-2 (WT) in the ER and mitochondria. We found that mt enhanced thapsigargin and tunicamycin-induced apoptosis through ER stress-mediated apoptosis but not through the death receptor- and mitochondria-dependent apoptosis, while WT prevented thapsigargin- and tunicamycin-induced apoptosis. In addition, mt depleted Ca in the ER lumen and also increased the expression of SOCE-related molecules. Therefore, a massive Ca influx via SOCE contributed to caspase activation and apoptosis. Furthermore, inhibiting SOCE or chelating either extracellular or intracellular Ca inhibited mt-mediated apoptosis. In brief, our results explored the critical role of Bcl-2 in Ca homeostasis and the modulation of ER stress.
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http://dx.doi.org/10.1038/s41420-018-0039-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841437PMC
December 2018

Revealing the three dimensional architecture of focal adhesion components to explain Ca-mediated turnover of focal adhesions.

Biochim Biophys Acta Gen Subj 2017 Mar 5;1861(3):624-635. Epub 2017 Jan 5.

Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan; Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan 701, Taiwan. Electronic address:

Background: Focal adhesions (FAs) are large, dynamic protein complexes located close to the plasma membrane, which serve as the mechanical linkages and a biochemical signaling hub of cells. The coordinated and dynamic regulation of focal adhesion is required for cell migration. Degradation, or turnover, of FAs is a major event at the trailing edge of a migratory cell, and is mediated by Ca/calpain-dependent proteolysis and disassembly. Here, we investigated how Ca influx induces cascades of FA turnover in living cells.

Methods: Images obtained with a total internal reflection fluorescence microscope (TIRFM) showed that Ca ions induce different processes in the FA molecules focal adhesion kinase (FAK), paxillin, vinculin, and talin. Three mutated calpain-resistant FA molecules, FAK-V744G, paxillin-S95G, and talin-L432G, were used to clarify the role of each FA molecule in FA turnover.

Results: Vinculin was resistant to degradation and was not significantly affected by the presence of mutated calpain-resistant FA molecules. In contrast, talin was more sensitive to calpain-mediated turnover than the other molecules. Three-dimensional (3D) fluorescence imaging and immunoblotting demonstrated that outer FA molecules were more sensitive to calpain-mediated proteolysis than internal FA molecules. Furthermore, cell contraction is not involved in degradation of FA.

Conclusions: These results suggest that Ca-mediated degradation of FAs was mediated by both proteolysis and disassembly. The 3D architecture of FAs is related to the different dynamics of FA molecule degradation during Ca-mediated FA turnover.

General Significance: This study will help us to clearly understand the underlying mechanism of focal adhesion turnover by Ca.
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http://dx.doi.org/10.1016/j.bbagen.2017.01.002DOI Listing
March 2017

FOXM1 confers to epithelial-mesenchymal transition, stemness and chemoresistance in epithelial ovarian carcinoma cells.

Oncotarget 2015 Feb;6(4):2349-65

Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Chemoresistance to anti-cancer drugs substantially reduces survival in epithelial ovarian cancer. In this study, we showed that chemoresistance to cisplatin and paclitaxel induced the epithelial-mesenchymal transition (EMT) and a stem cell phenotype in ovarian cancer cells. Chemoresistance was associated with the downregulation of epithelial markers and the upregulation of mesenchymal markers, EMT-related transcription factors, and cancer stem cell markers, which enhanced invasion and sphere formation ability. Overexpression of FOXM1 increased cisplatin-resistance and sphere formation in cisplatin-sensitive and low FOXM1-expressing ovarian cancer cells. Conversely, depletion of FOXM1 via RNA interference reduced cisplatin resistance and sphere formation in cisplatin-resistant and high FOXM1-expressing cells. Overexpression of FOXM1 also increased the expression, nuclear accumulation, and activity of β-CATENIN in chemoresistant cells, whereas downregulation of FOXM1 suppressed these events. The combination of cisplatin and the FOXM1 inhibitor thiostrepton inhibited the expression of stem cell markers in chemoresistant cells and subcutaneous ovarian tumor growth in mouse xenografts. In an analysis of 106 ovarian cancer patients, high FOXM1 levels in tumors were associated with cancer progression and short progression-free intervals. Collectively, our findings highlight the importance of FOXM1 in chemoresistance and suggest that FOXM1 inhibitors may be useful for treatment of ovarian cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385856PMC
http://dx.doi.org/10.18632/oncotarget.2957DOI Listing
February 2015

Overview of fetal growth retardation/restriction.

Taiwan J Obstet Gynecol 2014 Sep;53(3):435-40

Department of Obstetrics and Gynecology, Chi Mei Medical Center, Liouying, Tainan, Taiwan.

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http://dx.doi.org/10.1016/j.tjog.2014.01.003DOI Listing
September 2014

Enhanced myometrial autophagy in postpartum uterine involution.

Taiwan J Obstet Gynecol 2014 Sep;53(3):293-302

Department of Obstetrics and Gynecology, Chi Mei Medical Center, Liouying, Tainan, Taiwan; Department of Obstetrics and Gynecology, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Objective: To understand the mechanisms of postpartum uterine involution, we investigated the uterine myometrial changes during pregnancy and the postpartum period.

Materials And Methods: Nine groups of uterine myometrial samples from mice (n = 4) were collected on gestational Day 0 (nonpregnant), Day 1, Day 2, Day 7, Day 14, and Day 21 and on postpartum Day 1, Day 2, and Day 7. Human samples of uterine myometrium on term (n = 1) and postpartum Day 1 (n = 2) were also collected. Ki-67 immunostaining was used to determine myometrial proliferation. For cell hypertrophy analysis, organelle proteins, β-actin, prohibin, calnexin, and golgin-97 were analyzed by Western blotting. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and evaluation of activated caspase-3 expression by Western blot analysis assay were used to detect apoptosis. Autophagy was assayed via the evaluation of LC3 expression by Western blotting, immunohistochemistry, and autophagosomes by electron microscopy.

Results: Uterine myocytes proliferated during the early stage of gestation with a peak at Day 2, whereas myocyte hypertrophy with increased cellular organelle production occurred gradually in later stages of pregnancy. Postpartum autophagy developed abruptly in uterine myocytes without obvious apoptosis.

Conclusion: Autophagy of myocytes may play an important role in uterine involution. These results have implications for our understanding of myometrial functional adaptations during pregnancy and the physiological role of autophagy in the uterine remodeling events in the postpartum period.
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http://dx.doi.org/10.1016/j.tjog.2013.01.030DOI Listing
September 2014

Rapid progression of synchronous ovarian and endometrial cancers with massive omental carcinomatosis.

Taiwan J Obstet Gynecol 2012 Sep;51(3):452-4

Department of Obstetrics and Gynecology, Chi Mei Medical Center, Tainan, Taiwan.

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http://dx.doi.org/10.1016/j.tjog.2012.07.027DOI Listing
September 2012

Postpartum hemorrhage of genital tract origin.

Taiwan J Obstet Gynecol 2010 Dec;49(4):513-4

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http://dx.doi.org/10.1016/S1028-4559(10)60106-4DOI Listing
December 2010

Post-delivery complex partial seizure mimicking eclampsia.

Taiwan J Obstet Gynecol 2010 Sep;49(3):370-2

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http://dx.doi.org/10.1016/S1028-4559(10)60078-2DOI Listing
September 2010

Hypoxia and metabolic phenotypes during breast carcinogenesis: expression of HIF-1alpha, GLUT1, and CAIX.

Virchows Arch 2010 Jul 5;457(1):53-61. Epub 2010 Jun 5.

Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Hypoxia and acidosis are microenvironmental selection forces during somatic evolution in breast carcinogenesis. The effect of cobalt chloride (CoCl(2))-induced hypoxia on the expression of hypoxia-inducible factor (HIF)-1alpha, glucose transporter 1 (GLUT1), and carbonic anhydrase IX (CAIX) was assessed in breast cancer cells derived from primary sites (HCC1395 and HCC1937) and metastatic sites (MCF-7 and MDA-MB-231) by reverse transcriptase-polymerase chain reaction and immunoblotting. We analyzed these proteins' expression in tissue samples from normal breast tissue, usual ductal hyperplasia (DH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) using immunohistochemistry. CAIX mRNA was expressed constitutively in MDA-MB-231 cells but not in the other three cell lines. CAIX mRNA expression was increased after CoCl(2)-induced hypoxia in all four breast cancer cell lines. The expression of HIF-1alpha and GLUT1 proteins was increased after CoCl(2)-induced hypoxia in all breast cancer cell lines tested. Hypoxia significantly increased CAIX protein expression in primary cancer cells but not in metastatic ones. HIF-1alpha was not expressed in benign breast tissue, whereas it was significantly expressed in DH, ADH, DCIS, and IDC (p < 0.001). GLUT1 and CAIX were expressed only in DCIS (56.8% and 25.0%) and IDC (44.1% and 30.5%), with higher expression in high grade DCIS than low/intermediate grade DCIS (79.2% vs. 30.0%, p = 0.001 and 37.5% vs. 10.0%, p = 0.036, respectively). High CAIX expression was significantly associated with poor histological grade of IDC (p = 0.005). During breast carcinogenesis, the role of HIF-1alpha changes from response to proliferation to tumor progression. GLUT1 expression (glycolytic phenotype) and CAIX expression (acid-resistant phenotype) may result in a powerful adaptive advantage and represent an aggressive phenotype.
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http://dx.doi.org/10.1007/s00428-010-0938-0DOI Listing
July 2010

Cobalt chloride-induced hypoxia modulates the invasive potential and matrix metalloproteinases of primary and metastatic breast cancer cells.

Anticancer Res 2009 Aug;29(8):3131-8

Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, PRC.

Background: Tumor hypoxia promotes cancer progression. Matrix metalloproteinases (MMPs) are required for breast cancer cell invasion.

Materials And Methods: The effect of cobalt chloride (CoCl(2))-stimulated hypoxia on invasion potential and the expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs) were investigated in four breast cancer cell lines, derived from primary sites (HCC1395 and HCC1937) and metastatic sites (MCF-7 and MDA-MB-231).

Results: CoCl(2)-induced hypoxia induced HIF-1alpha protein expression in all four cell lines. Hypoxia significantly increased the invasiveness of HCC1395 cells, which did not correlate with a change of any one MMP. Constitutive MMP expression was different between primary and metastatic breast cancer cells. MMP-2 and MMP-9 measured by RT-PCR and zymography were notably expressed in primary cancer cells but not apparent in metastatic ones. MMP-7 was also highly expressed in primary cancer cells. Hypoxia increased the expression of MMP-1, -10 and -13 in metastatic breast cancer cells, whereas only MMP-13 was up-regulated in primary HCC1937 cells by hypoxic stimulation. TIMPs were not altered by hypoxia, except for TIMP-4 which was down-regulated in MDA-MB-231 cells.

Conclusion: This study demonstrated a cell line-specific effect of hypoxia on invasive potential and differential expression of constitutive MMPs in primary versus metastatic breast cancer cells, i.e. primary cancer cells expressed a wider range of MMPs, in particular MMP-2, -7 and -9, than the metastatic ones. The data suggest that MMPs play no crucial roles in hypoxia-induced tumor progression in primary breast cancer cells.
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August 2009

Shallot and licorice constituent isoliquiritigenin arrests cell cycle progression and induces apoptosis through the induction of ATM/p53 and initiation of the mitochondrial system in human cervical carcinoma HeLa cells.

Mol Nutr Food Res 2009 Jul;53(7):826-35

Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

This study is the first to investigate the anticancer effect of isoliquiritigenin (ISL) in human cervical carcinoma HeLa cells. The results reveal that ISL inhibits HeLa cells by blocking cell cycle progression in the G2/M phase and inducing apoptosis. Blockade of cell cycle is associated with increased activation of ataxia telangiectasia-mutated (ATM). Activation of ATM by ISL phosphorylated p53 at Serine15, resulting in increased stability of p53 by decreasing p53 and murine double minute-2 (MDM2) interaction. In addition, ISL-mediated G2/M phase arrest was also associated with decreases in the amounts of cyclin B, cyclin A, cdc2, and cdc25C, and increases in the phosphorylation of Chk2, cdc25C, and cdc2. The specific ATM inhibitor caffeine significantly decreased ISL-mediated G2/M arrest by inhibiting the phosphorylation of p53 (Serine15) and Chk2. ISL induced apoptotic cell death is associated with changes in the expression of Bax and Bak, decreasing levels of Bcl-2 and Bcl-X(L), and subsequently triggering mitochondrial apoptotic pathway. In addition, pretreatment of cells with caspase-9 inhibitor blocked ISL-induced apoptosis, indicating that caspase-9 activation is involved in ISL-mediated HeLa cell apoptosis. These findings suggest that ISL may be a promising chemopreventive agent against human uterine cervical cancer.
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http://dx.doi.org/10.1002/mnfr.200800288DOI Listing
July 2009

Cathepsin L mediates resveratrol-induced autophagy and apoptotic cell death in cervical cancer cells.

Autophagy 2009 May 19;5(4):451-60. Epub 2009 May 19.

Institute of Clinical Medicine, Department of Obstetrics and Gynecology, National Cheng Kung University Medical College, 1 Dashiue Road, Tainan, Taiwan.

Cathepsins have long been considered as housekeeping molecules. However, specific functions have also been attributed to each of these lysosomal proteases. Squamous cell carcinoma antigen (SCCA) 1, widely expressed in various uterine cervical cells, is an endogenous cathepsin (cat) L inhibitor. In this study, we investigated whether the cat L-SCCA 1 lysosomal pathway and autophagy were involved in resveratrol (RSV)-induced cytotoxicity in cervical cancer cells. RSV induced GFP-LC3 aggregation as well as increased the presence of LC3-II and autophagosomes as was revealed by electron microscopy in cervical cancer cells. Prolonged treatment of RSV induced cytosolic translocation of cytochrome c, caspase 3 activation and apoptotic cell death. This apoptotic effect was abrogated by trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane, an inhibitor of cat B and L, but not by pepstatin A, an inhibitor of cat D. As cervical cancer cells express little cat B, we further studied the role of cat L. RSV induced dissipation of the lysosomal membrane permeability (LMP), leakage and increased cytosolic expression and activity of cat L. Inhibition of cat L by small interference RNA (siRNA) protected cells from RSV-induced cytotoxicity. In contrast, inhibition of SCCA 1 by siRNA promoted RSV-induced cytotoxicity. Inhibition of autophagic response by wortmannin (WT) or asparagine (ASP) resulted in decreased early LC3-II formation, reduced LMP, and abolishment of the increase in RSV-induced cell death. In conclusion, we have identified a new cytotoxic mechanism in which the lysosomal enzyme cat L acts as a death signal integrator in cervical cancer cells. Furthermore, SCCA 1 may play an antiapoptotic role through anti-cat L activity.
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http://dx.doi.org/10.4161/auto.5.4.7666DOI Listing
May 2009

Association of extremely skewed X-chromosome inactivation with Taiwanese women presenting with recurrent pregnancy loss.

J Formos Med Assoc 2008 Apr;107(4):340-3

Department of Obstetrics and Gynecology, National Cheng Kung University College of Medicine, Tainan, Taiwan.

X-chromosome inactivation (XCI) is a phenomenon that occurs in female mammals. Typically, maternally and paternally-derived X chromosomes are inactivated at approximately the same frequency. If preferential inactivation occurs, the person is considered to have skewed XCI. Skewed XCI has been reported to occur more frequently in women who experience recurrent pregnancy loss (RPL). In this study, we sought to investigate if there is an association between skewed XCI and unexplained RPL in Taiwanese women. A total of 194 women who had experienced unexplained RPL were recruited into the study. Human androgen receptor or DXS6673E and DX15-134 loci were used in the XCI assay. The results of our study suggested that a cut-off point less than 90% may not be justified for skewed XCI. Only extremely skewed (more than 95%) XCI is associated with RPL. Extremely skewed XCI occurs in a subset of Taiwanese women with RPL.
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http://dx.doi.org/10.1016/S0929-6646(08)60096-0DOI Listing
April 2008

Uterine choriocarcinoma accompanied by an extremely high human chorionic gonadotropin level and thyrotoxicosis.

J Obstet Gynaecol Res 2008 Apr;34(2):274-8

Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

The conventional treatments given to a 24-year-old woman with metastatic uterine choriocarcinoma and clinical and biochemical thyrotoxicosis did not appear to have any effect, probably due to an extremely high serum human chorionic gonadotropin (hCG) level which was up to 11,910,000 mIU/mL, and were initially underscored in light of the 'high-dose hook effect'. To our knowledge, no extremely high hCG level in a uterine choriocarcinoma patient has been reported in the literature. Her decapacitating symptoms subsided after the first course of chemotherapy by etoposide, methotrexate, and actinomycin D-cyclophosphamide and vincristine (EMA-CO) regimen. The serum hCG level, which reflects the quantification of host tumor burden, returned to the reference range after the fifth course of chemotherapy and the thyroid function reached euthyroid status before the third course of chemotherapy; two final courses were administered after the hCG level became undetectable. Two years after remission of disease, the patient experienced a normal pregnancy, and a term baby girl was delivered vaginally. No recurrence of uterine choriocarcinoma has been noted for 7 years.
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http://dx.doi.org/10.1111/j.1447-0756.2008.00770.xDOI Listing
April 2008

Chromosomal gain of 3q and loss of 11q often associated with nodal metastasis in early stage cervical squamous cell carcinoma.

J Formos Med Assoc 2007 Nov;106(11):894-902

Department of Obstetrics and Gynecology, Chi Mei Medical Center, Tainan, Taiwan.

Background/purpose: Cervical cancer remains a health problem among women worldwide. Delineation of genetic changes is critical to understanding the molecular basis of tumor progression, as well as for identifying genetic markers for early identification of patients at high risk for a poor outcome.

Methods: To provide comparative genomic hybridization data for cervical squamous cell carcinoma in Taiwan, and to gain further insight into genetic markers associated with lymph node metastasis of this disease, we performed comparative genomic hybridization analysis of 30 consecutive cases of cervical squamous cell carcinoma (24 stage IB and 6 stage IIB).

Results: The results disclosed that higher staged tumors or those with lymph node metastasis had more chromosomal imbalances. The commonly recurrent chromosomal imbalances were gains of 3q (46.7%), 1q (36.7%) and 8q (20.0%) and losses of 11q (36.7%), 3p (33.3%), 6q (23.3%), and 2q (20.0%). The frequencies of these chromosomal imbalances in stage IB and IIB tumors did not differ significantly. However, when compared with tumors without lymph node metastasis, the loss of 11q14-q22 (5/9 vs. 3/21, p = 0.019) and gains of 3q11-q22 and 3q26-qter (6/9 vs. 5/21, p = 0.026) were significantly more prevalent in tumors with lymph node metastasis.

Conclusion: The results suggest that certain tumor-associated genes residing on 3q and 11q warrant further investigation to elucidate their role in the progression of this disease.
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http://dx.doi.org/10.1016/S0929-6646(08)60059-5DOI Listing
November 2007

Roles for hypoxia-regulated genes during cervical carcinogenesis: somatic evolution during the hypoxia-glycolysis-acidosis sequence.

Gynecol Oncol 2008 Feb 4;108(2):377-84. Epub 2007 Dec 4.

Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan.

Objectives: Malignant phenotypic traits are caused by microenvironmental selection pressures during carcinogenesis. Hypoxia can drive a tumor toward a more aggressive malignant phenotype. The objective was to better understand the role of the hypoxia-regulated genes in cervical carcinogenesis.

Methods: We analyzed the expression of the hypoxia-regulated genes, including hypoxia-inducible factor-1alpha (HIF-1alpha), erythropoietin (Epo), vascular endothelial growth factor (VEGF), glucose transporter 1 (GLUT1), carbonic anhydrase IX (CAIX), and MET, in cervical cell lines and human tissue samples of cervical intraepithelial neoplasia (CIN I-III) and invasive squamous cell carcinoma (ISCC).

Results: CAIX and MET were expressed in cervical carcinoma cell lines, but not in normal or human papillomavirus-immortalized cervical cells. In clinical tissue samples, Epo, VEGF, GLUT1, and CAIX were not detected in normal squamous epithelia. GLUT1 was expressed in nearly all cases of CIN and ISCC, however, CAIX was expressed only in CIN III and ISCC. HIF-1alpha and MET expression was confined to the basal cells in normal squamous epithelia and was detected in the dysplastic cells of CIN and ISCC.

Conclusions: The role of HIF-1alpha and MET changes from response to proliferation to tumor progression during cervical carcinogenesis. GLUT1 expression, a glycolytic phenotype adaptive to glycolysis, occurs early during cervical carcinogenesis and is a specific marker for dysplasia or carcinoma. MET and CAIX may contribute tumor progression in later stage. CAIX expression, an acid-resistant phenotype, may be a powerful adaptive advantage during carcinogenesis. Successful adaptation to the hypoxia-glycolysis-acidosis sequence in a microenvironment is crucial during carcinogenesis.
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http://dx.doi.org/10.1016/j.ygyno.2007.10.034DOI Listing
February 2008

Alterations of metastasis-related genes identified using an oligonucleotide microarray of genistein-treated HCC1395 breast cancer cells.

Nutr Cancer 2007 ;58(2):239-46

Department of Pathology, Yung Kung Campus, Chi MeiMedical Center, Tainan, 710, Taiwan.

Genistein, one of the major isoflavones, potently inhibits the growth and metastasis of breast cancer. However, the precise molecular mechanism in metastasis inhibition is not clear. We investigated the effect of genistein in HCC1395 cells, a cell line derived from an early-stage primary breast cancer. Genistein dose dependently both decreased cell viability and inhibited the invasion potential. We used human oligonucleotide microarrays to determine the gene expression profile altered by genistein treatment. TFPI-2, ATF3, DNMT1, and MTCBP-1, which inhibit invasion and metastasis, were upregulated, and MMP-2, MMP-7, and CXCL12, which promote invasion and metastasis, were downregulated. We used quantitative real-time polymerase chain reaction to verify the microarray data at the mRNA level. We conclude that genistein-induced alternations of gene expression involving metastasis may be exploited for devising chemopreventive and therapeutic strategies, particularly for early-stage breast cancer.
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http://dx.doi.org/10.1080/01635580701328636DOI Listing
October 2007

Fetal congenital lobar emphysema.

Taiwan J Obstet Gynecol 2007 Mar;46(1):73-6

Department of Obstetrics and Gynecology, Chi Mei Medical Center, Liou-Ying Campus, Tainan, Taiwan.

Objective: To report a rare fetal congenital lung anomaly characterized by over inflation of a pulmonary lobe.

Case Report: A 28-year-old systemic lupus erythematous mother, gravida 1 para 0, who had normal prenatal care in our department, was admitted for labor pain and an abnormal fetal heart location was noted incidentally during labor. The baby showed rib retraction in room air but no obvious cyanotic change after delivery. Both the fetus chest X-ray and ultrasound showed a hyperechogenic tumor in the left thoracic cavity with a right-side-shifted heart and trachea. Computed tomography showed a hypodense and multiseptal tumor in the left thoracic cavity with right-sided shift of the heart and trachea. It was a soft, solid tumor in the parenchyma of the left lung and the histopathology confirmed it to be benign congenital lobar emphysema.

Conclusion: The favorable outcome in both asymptomatic and mildly symptomatic children suggests that a nonsurgical approach should be considered for these patients.
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http://dx.doi.org/10.1016/S1028-4559(08)60113-8DOI Listing
March 2007

Ruptured tubo-ovarian abscess in a postmenopausal woman presenting with septic shock: a case report and literature review.

Taiwan J Obstet Gynecol 2006 Mar;45(1):89-91

Department of Obstetrics and Gynecology, Chi Mei Hospital, Liou-Ying, Tainan, Taiwan.

Objective: To report a case of a ruptured tubo-ovarian abscess which induced septic shock in a postmenopausal woman.

Case Report: A 53-year-old postmenopausal woman was transferred to our emergency department for drowsiness, hypotension, and lower abdominal discomfort. Transabdominal sonography and computed tomography showed a large pelvic tumor over the left adnexa with some ascites. The uterus and other adnexa were unremarkable. Laboratory data, including blood count and electrolytes, showed leukocytosis and azotemia. Under suspicion of a ruptured adnexal tumor, laparotomy was performed and showed a large ruptured tubo-ovarian tumor arising from the left adnexa with intra-abdominal pus formation. Subtotal hysterectomy and bilateral salpingo-oophorectomy led to massive bleeding during manipulation of the left adnexa because of the necrotic change in the left infundibulopelvic vessels. Deep vein thrombosis and wound disruption occurred after the operation, but, fortunately, she recovered 1 month later.

Conclusion: Tubo-ovarian abscesses in postmenopausal women are uncommon but should be kept in mind with a pelvic tumor accompanied by septic shock, as this may cause a terrible outcome and other sequelae.
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http://dx.doi.org/10.1016/s1028-4559(09)60202-3DOI Listing
March 2006

Isolated congenital diaphragmatic hernia in the third trimester: a case report and literature review.

Taiwan J Obstet Gynecol 2006 Mar;45(1):83-5

Department of Obstetrics and Gynecology, Chi Mei Hospital, Liou-Ying, Tainan, Taiwan.

Objective: To report a rare congenital anomaly, a right diaphragmatic hernia, in a near-term baby.

Case Report: A 40-year-old female, gravida 3, para 2, had undergone regular prenatal care in our department since the early second trimester. She underwent amniocentesis at 16 weeks of gestation. The result showed normal 46,XY. Fetal growth was appropriate throughout the pregnancy. A small heart with marked left-side deviation was noted in the third trimester. The heart rate was less than 25% of normal. A homogenous mass with centralized vessels was noted in the fetus's right chest. The baby showed respiratory distress immediately after delivery. Imaging studies after birth proved there was a right diaphragmatic hernia with severe pulmonary hypertension and poor lung function.

Conclusion: Right congenital diaphragmatic hernia is rare. A prenatal diagnosis is difficult to make in the second trimester. Prognosis is greatly influenced by the associated abnormalities.
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http://dx.doi.org/10.1016/S1028-4559(09)60200-XDOI Listing
March 2006

Ultrasonographic evaluation of the change in uterine fibroids induced by treatment with a GnRH analog.

Taiwan J Obstet Gynecol 2006 Jun;45(2):124-8

Department of Obstetrics and Gynecology, Chi Mei Hospital, Liouying, Tainan, Taiwan.

Objective: To investigate the change in volume of uterine fibroids after GnRH analog (GnRHa) treatment.

Materials And Methods: Twenty-five patients who had a uterine leiomyoma were included in this study. Four of them were lost to follow-up during the study, and a myomectomy was performed on the remaining subjects. All of these patients received two doses, 4 weeks apart, each of 3.75 mg leuprorelin acetate subcutaneously (Leuplin depot, a GnRHa) before the operation. The vascularization index (VI), flow index (FI), vascularization-flow index (VFI), pulsative index (PI), resistance index (RI), vascular patterns (histogram), blood flows, and sizes (volume and largest diameter) of each fibroid were measured with power Doppler by the same technician every month before the operation. In addition, the total blood loss and time required for each operation were also recorded.

Results: Results of this study showed that the volume of the uterus and the fibroids, but not the vascularity, including VI, FI, VFI, PI and RI, decreased significantly after two doses of GnRHa treatment. In addition, blood loss during the operation decreased significantly compared to an untreated group.

Conclusion: We found that the volumes of the uterus and fibroids decreased significantly after treatment with two consecutive doses (given a month apart) of GnRHa. The 3D color Doppler including a histogram and blood flow parameters is another useful tool for fibroid evaluation.
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http://dx.doi.org/10.1016/S1028-4559(09)60209-6DOI Listing
June 2006

Discordant responses to progestin in a patient with uterine low-grade smooth-muscle tumors metastatic to the lung.

J Obstet Gynaecol Res 2005 Oct;31(5):394-8

Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan, Taiwan.

A 58-year-old woman presented with pelvic, para-aortic masses and two isolated nodules in the right lung 6 years after hysterectomy and bilateral salpingo-oophorectomy for uterine leiomyoma. Laparotomy was carried out and all the intra-abdominal tumors were excised; pathology showed metastatic low-grade leiomyosarcomas. Immunohistochemical staining revealed a high expression level of estrogen and progesterone receptors in these tumors. The pulmonary nodules were left and the patient was given oral medroxyprogesterone acetate 200 mg daily after the operation. One of the pulmonary masses regressed progressively and had disappeared 7 months later on chest X-ray examination. However, the other was persistent. She then received wedge resection to excise the pulmonary nodule, which showed the same histologic pattern as the abdomen masses. However, the immunohistochemical staining on this nodule showed positive estrogen receptor expression but was negative for progesterone receptor expression. After the operation, she maintained progestin treatment and was tumor free for the following 12 months.
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http://dx.doi.org/10.1111/j.1447-0756.2005.00308.xDOI Listing
October 2005