20 results on '"Chiho Koi"'
Search Results
2. Endoplasmic stress‐inducing variants in <scp> CPB1 </scp> and <scp> CPA1 </scp> and risk of pancreatic cancer: A case‐control study and meta‐analysis
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Ki Byung Song, Ralph H. Hruban, Alison P. Klein, Ryo Sugimine, Michael Goggins, Mohamad Dbouk, Nicholas J. Roberts, Anne Macgregor-Das, Toshiya Abe, Makoto Kawamoto, Shiro Kohi, Daniel A. Laheru, Chiho Koi, and Michael Borges
- Subjects
Cancer Research ,business.industry ,Endoplasmic reticulum ,Case-control study ,Odds ratio ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Pancreatic cancer ,medicine ,Cancer research ,Unfolded protein response ,Pancreatitis ,Pancreas ,business ,Gene - Abstract
Gene variants that encode pancreatic enzymes with impaired secretion can induce pancreatic acinar endoplasmic reticulum (ER) stress, cellular injury and pancreatitis. The role of such variants in pancreatic cancer risk has received little attention. We compared the prevalence of ER stress-inducing variants in CPA1 and CPB1 in patients with pancreatic ductal adenocarcinoma (PDAC cases), enrolled in the National Familial Pancreas Tumor Registry, to their prevalence in non-cancer controls in the Genome Aggregation Database (gnomAD). Variants of unknown significance were expressed and variants with reduced secretion assessed for ER stress induction. In vitro assessments were compared with software predictions of variant function. Protein variant software was used to assess variants found in only one gnomAD control ("n-of-one" variants). A meta-analysis of prior PDAC case/control studies was also performed. Of the 1385 patients with PDAC, 0.65% were found to harbor an ER stress-inducing variant in CPA1 or CPB1, compared to 0.17% of the 64,026 controls (Odds Ratio (OR): 3.80 [1.92-7.51] P=0.0001). ER stress-inducing variants in the CPA1 gene were identified in 4 of 1385 PDAC cases versus 77 of 64,026 gnomAD controls (OR: 2.4 [0.88-6.58], p=0.087), and variants in CPB1 were detected in 5 of 1385 cases versus 33 of 64,026 controls (OR: 7.02 [2.74-18.01], p=0.0001). Meta-analysis demonstrated strong associations for pancreatic cancer and ER-stress inducing variants for both CPA1 (OR: 3.65 [1.58, 8.39], p
- Published
- 2021
3. UBE2L6 is Involved in Cisplatin Resistance by Regulating the Transcription of ABCB6
- Author
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Kiyoshi Yoshino, Yasuo Morimoto, Chiho Koi, Hiroto Izumi, Tomoko Kurita, and Midori Murakami
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Cancer Research ,Cell Survival ,Antineoplastic Agents ,ATP-binding cassette transporter ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Transcription (biology) ,Gene expression ,Tumor Cells, Cultured ,medicine ,Humans ,RNA, Messenger ,Gene ,Cell Proliferation ,030304 developmental biology ,Pharmacology ,Cisplatin ,0303 health sciences ,Messenger RNA ,Dose-Response Relationship, Drug ,biology ,Chemistry ,ABCB6 ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Ubiquitin-Conjugating Enzymes ,biology.protein ,Cancer research ,Molecular Medicine ,ATP-Binding Cassette Transporters ,Drug Screening Assays, Antitumor ,medicine.drug - Abstract
Background: Cisplatin is an important anticancer agent in cancer chemotherapy, but when resistant cells appear, treatment becomes difficult, and the prognosis is poor. Objective: In this study, we investigated the gene expression profile in cisplatin sensitive and resistant cells, and identified the genes involved in cisplatin resistance. Methods: Comparison of gene expression profiles revealed that UBE2L6 mRNA is highly expressed in resistant cells. To elucidate whether UBE2L6 is involved in the acquisition of cisplatin resistance, UBE2L6- overexpressing cells established from cisplatin-sensitive cells and UBE2L6-silenced cells developed from cisplatin- resistant cells were generated, and the sensitivity of cisplatin was examined. Results: The sensitivity of the UBE2L6-overexpressing cells did not change compared with the control cells, but the UBE2L6-silenced cells were sensitized to cisplatin. To elucidate the mechanism of UBE2L6 in cisplatin resistance, we compared the gene expression profiles of UBE2L6-silenced cells and control cells and found that the level of ABCB6 mRNA involved in cisplatin resistance was decreased. Moreover, ABCB6 promoter activity was partially suppressed in UBE2L6-silenced cells. Conclusion: These results suggest that cisplatin-resistant cells have upregulated UBE2L6 expression and contribute to cisplatin resistance by regulating ABCB6 expression at the transcriptional level. UBE2L6 might be a molecular target that overcomes cisplatin resistance.
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- 2020
4. Detection of Circulating Tumor DNA in Patients with Pancreatic Cancer Using Digital Next-Generation Sequencing
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Toshiya Abe, Alison P. Klein, Ralph H. Hruban, Koji Tamura, Christopher L. Wolfgang, Jun Yu, Miguel Chuidian, Anne Macgregor-Das, Koji Shindo, Jose Alejandro Almario, Michael Goggins, Chiho Koi, Marco Dal Molin, Michael Borges, Madeline Ford, Marcia I. Canto, James R. Eshleman, Yoshihiko Sadakari, Jin He, Masaya Suenaga, Richard A. Burkhart, and Shiro Kohi
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Adult ,Male ,0301 basic medicine ,Pancreatic Intraductal Neoplasms ,medicine.disease_cause ,Polymerase Chain Reaction ,Article ,DNA sequencing ,Circulating Tumor DNA ,Pathology and Forensic Medicine ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pancreatic cancer ,Biomarkers, Tumor ,Chromogranins ,GTP-Binding Protein alpha Subunits, Gs ,GNAS complex locus ,Humans ,Medicine ,Codon ,Aged ,Aged, 80 and over ,Mutation ,biology ,business.industry ,High-Throughput Nucleotide Sequencing ,Middle Aged ,medicine.disease ,Pancreatic Neoplasms ,030104 developmental biology ,chemistry ,Circulating tumor DNA ,Case-Control Studies ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Molecular Medicine ,Female ,KRAS ,business ,DNA ,Cytosine ,Carcinoma, Pancreatic Ductal - Abstract
Circulating tumor DNA (ctDNA) measurements can be used to estimate tumor burden, but avoiding false-positive results is challenging. Herein, digital next-generation sequencing (NGS) is evaluated as a ctDNA detection method. Plasma KRAS and GNAS hotspot mutation levels were measured in 140 subjects, including 67 with pancreatic ductal adenocarcinoma and 73 healthy and disease controls. To limit chemical modifications of DNA that yield false-positive mutation calls, plasma DNA was enzymatically pretreated, after which DNA was aliquoted for digital detection of mutations (up to 384 aliquots/sample) by PCR and NGS. A digital NGS score of two SDs above the mean in controls was considered positive. Thirty-seven percent of patients with pancreatic cancer, including 31% of patients with stages I/II disease, had positive KRAS codon 12 ctDNA scores; only one patient had a positive GNAS mutation score. Two disease control patients had positive ctDNA scores. Low-normal-range digital NGS scores at mutation hotspots were found at similar levels in healthy and disease controls, usually at sites of cytosine deamination, and were likely the result of chemical modification of plasma DNA and NGS error rather than true mutations. Digital NGS detects mutated ctDNA in patients with pancreatic cancer with similar yield to other methods. Detection of low-level, true-positive ctDNA is limited by frequent low-level detection of false-positive mutation calls in plasma DNA from controls.
- Published
- 2020
5. Endoplasmic stress-inducing variants in CPB1 and CPA1 and risk of pancreatic cancer: A case-control study and meta-analysis
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Makoto, Kawamoto, Shiro, Kohi, Toshiya, Abe, Mohamad, Dbouk, Anne, Macgregor-Das, Chiho, Koi, Ki-Byung, Song, Michael, Borges, Ryo, Sugimine, Daniel, Laheru, Ralph H, Hruban, Nicholas, Roberts, Alison P, Klein, and Michael, Goggins
- Subjects
Pancreatic Neoplasms ,Risk ,Carboxypeptidases A ,Case-Control Studies ,Genetic Variation ,Humans ,Genetic Predisposition to Disease ,Endoplasmic Reticulum Stress ,Carboxypeptidase B ,Article ,Carcinoma, Pancreatic Ductal - Abstract
Gene variants that encode pancreatic enzymes with impaired secretion can induce pancreatic acinar endoplasmic reticulum (ER) stress, cellular injury and pancreatitis. The role of such variants in pancreatic cancer risk has received little attention. We compared the prevalence of ER stress-inducing variants in CPA1 and CPB1 in patients with pancreatic ductal adenocarcinoma (PDAC cases), enrolled in the National Familial Pancreas Tumor Registry, to their prevalence in non-cancer controls in the Genome Aggregation Database (gnomAD). Variants of unknown significance were expressed and variants with reduced secretion assessed for ER stress induction. In vitro assessments were compared with software predictions of variant function. Protein variant software was used to assess variants found in only one gnomAD control (“n-of-one” variants). A meta-analysis of prior PDAC case/control studies was also performed. Of the 1385 patients with PDAC, 0.65% were found to harbor an ER stress-inducing variant in CPA1 or CPB1, compared to 0.17% of the 64,026 controls (Odds Ratio (OR): 3.80 [1.92–7.51] P=0.0001). ER stress-inducing variants in the CPA1 gene were identified in 4 of 1385 PDAC cases versus 77 of 64,026 gnomAD controls (OR: 2.4 [0.88–6.58], p=0.087), and variants in CPB1 were detected in 5 of 1385 cases versus 33 of 64,026 controls (OR: 7.02 [2.74–18.01], p=0.0001). Meta-analysis demonstrated strong associations for pancreatic cancer and ER-stress inducing variants for both CPA1 (OR: 3.65 [1.58, 8.39], p
- Published
- 2021
6. Lovastatin induced Kruppel like factor 2 (KLF2), Kruppel like factor 6 (KLF6) and Ras homolog family member B (RHOB) genes and preferentially led to viability reduction of Cisplatin-resistant cells
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Yasuo Morimoto, Chiho Koi, Yukiko Yoshiura, Hiroto Izumi, Thuy Thi Nguyen, Tomoko Kurita, Midori Murakami, and Toru Hachisuga
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0301 basic medicine ,Cisplatin ,biology ,Chemistry ,Cell growth ,RHOB ,nutritional and metabolic diseases ,biology.organism_classification ,HeLa ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,HMG-CoA reductase ,polycyclic compounds ,biology.protein ,Cancer research ,medicine ,lipids (amino acids, peptides, and proteins) ,Viability assay ,Lovastatin ,medicine.drug - Abstract
It was reported that statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase that are used to prevent hypercholesterolemia, have antitumor activity in several cancers. In this study, we investigated the cell viability of statins in Cisplatin-resistant HCP4 and PCDP5 cells compared with their parent Hela and PC3 cells, respectively, and found that HCP4 and PCDP5 cells were 37-fold and 18-fold more resistant to Cisplatin but 13-fold and 7-fold more sensitive to Lovastatin by cell proliferation assay. Lovastatin induced the apoptosis of HCP4 cells more rapidly and to greater extent than in Hela cells as assessed by flow cytometry and western blotting analyses. The MVA pathway was not involved in this acquired Cisplatin resistance. To elucidate the mechanism underlying the reduced viability to Lovastatin, we performed cDNA microarray analysis and identified 65 and 54 genes that were induced more than 2-fold by Lovastatin in HCP4 and PCDP5 cells, respectively. Of these, only three genes, KLF2, KLF6, and RHOB, were commonly induced between HCP4 and PCDP5 cells. These mRNAs were strongly induced by Lovastatin with transcriptional regulation in HCP4 cells. Consistent with transcription, the protein expression of RHOB also was induced by Lovastatin. The induction of these genes was associated with cell cycle arrest and apoptosis. Combination treatment with Cisplatin and Lovastatin resulted in an agonistic effect in Hela and PC3 cells and an antagonistic effect in HCP4 and PCDP5 cells. These results suggest that statins might have the potential to overcome Cisplatin resistance as single-agent therapy.
- Published
- 2017
7. 17β-Estradiol induces proliferation of endometrial NK cells (CD56+) in postmenopausal women
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K Yoshimura, Toshinori Kawagoe, Toru Hachisuga, Chiho Koi, Tomoko Kurita, Masanori Hisaoka, T Sho, Yusuke Matsuura, and Seiji Kagami
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0301 basic medicine ,medicine.medical_specialty ,genetic structures ,Administration, Cutaneous ,Endometrium ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Hormone replacement therapy ,Cell Proliferation ,Postmenopausal women ,Lymphocytic infiltration ,Estradiol ,business.industry ,Estrogen Replacement Therapy ,Obstetrics and Gynecology ,General Medicine ,Middle Aged ,Killer Cells, Natural ,Postmenopause ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Female ,business - Abstract
The aim of this report was to evaluate the impact of hormone replacement therapy (HRT) on lymphocytic infiltration of the endometrium in postmenopausal women.This study included 58 Japanese patients who had undergone hysterectomy at the University Hospital of Occupational and Environmental Health, Japan. Before surgery, nine patients had received 17β-estradiol (E2), 0.72 mg transdermally for 2-8 weeks (E2 group); 16 patients had received an Estra-1,3,5(10)-triene-3,16α, 17β-triol (E3) vaginal tablet 0.5 mg per month five times (E3 group); and 19 patients had received 17β-estradiol, 0.62 mg, and norethindrone acetate (P), 2.70 mg for 3-16 weeks (E2 + P group). Fourteen patients received no HRT (control group). We examined uterine tissue specimens immunohistochemically for CD45+, CD3+, CD4+, CD8+, CD20+, CD56+, and Ki67 antigen-positive cells.The numbers of CD56 + cells were significantly increased in the E2 group compared with all other groups (E2 vs. E3: 7.0 vs. 0.75, p = 0.017; E2 vs. E2 + P: 7.0 vs. 0.58, p = 0.009; E2 vs.7.0 vs. 0.43, p = 0.010). The numbers of CD3+ cells were significantly increased in the E2 group compared with the control group (149.3 vs. 42.6, p = 0.008).17β-Estradiol induced the proliferation of endometrial uterine natural killer cells (CD56+) in postmenopausal women.
- Published
- 2017
8. Gene Variants That Affect Levels of Circulating Tumor Markers Increase Identification of Patients with Pancreatic Cancer
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Ralph H. Hruban, Miguel Chuidian, Shiro Kohi, Chiho Koi, Koji Tamura, Jin He, Marcia I. Canto, Mohamad Dbouk, Anne Macgregor-Das, Ki Byung Song, Toshiya Abe, Richard A. Burkhart, Madeline Ford, James R. Eshleman, Naoki Kitaoka, Michael Borges, Michael Goggins, Alison P. Klein, and Christopher L. Wolfgang
- Subjects
Oncology ,medicine.medical_specialty ,endocrine system diseases ,CA-19-9 Antigen ,Single-nucleotide polymorphism ,Article ,03 medical and health sciences ,0302 clinical medicine ,Carcinoembryonic antigen ,Internal medicine ,ABO blood group system ,Pancreatic cancer ,medicine ,Biomarkers, Tumor ,SNP ,Humans ,Tumor marker ,Hepatology ,biology ,business.industry ,Gastroenterology ,Cancer ,medicine.disease ,digestive system diseases ,Neoplasm Proteins ,Pancreatic Neoplasms ,030220 oncology & carcinogenesis ,Case-Control Studies ,biology.protein ,Cytokines ,030211 gastroenterology & hepatology ,CA19-9 ,business ,Carcinoma, Pancreatic Ductal - Abstract
Background & Aims Levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA-125) in blood are used as markers to determine the response of patients with cancer to therapy, but are not used to identify patients with pancreatic cancer. Methods We obtained blood samples from 504 patients undergoing pancreatic surveillance from 2002 through 2018 who did not develop pancreatic cancer and measured levels of the tumor markers CA19-9, CEA, CA-125, and thrombospondin-2. Single-nucleotide polymorphisms (SNPs) in FUT3, FUT2, ABO, and GAL3ST2 that have been associated with levels of tumor markers were used to establish SNP-defined ranges for each tumor marker. We also tested the association between additional SNPs (in FUT6, MUC16, B3GNT3, FAM3B, and THBS2) with levels of tumor markers. To calculate the diagnostic specificity of each SNP-defined range, we assigned the patients under surveillance into training and validation sets. After determining the SNP-defined ranges, we determined the sensitivity of SNP-adjusted tests for the tumor markers, measuring levels in blood samples from 245 patients who underwent resection for pancreatic ductal adenocarcinoma (PDAC) from 2010 through 2017. Results A level of CA19-9 that identified patients with PDAC with 99% specificity had 52.7% sensitivity. When we set the cut-off levels of CA19-9 based on each SNP, the test for CA19-9 identified patients with PDAC with 60.8% sensitivity and 98.8% specificity. Among patients with FUT3 alleles that encode a functional protein, levels of CA19-9 greater than the SNP-determined cut-off values identified 66.4% of patients with PDAC, with 99.3% specificity. In the validation set, levels of CEA varied among patients with vs without SNP in FUT2, by blood group, and among smokers vs nonsmokers; levels of CA-125 varied among patients with vs without the SNP in GAL3ST2. The use of the SNPs to define the ranges of CEA and CA-125 did not significantly increase the diagnostic accuracy of the assays for these proteins. Combining data on levels of CA19-9 and CEA, CA19-9 and CA-125, or CA19-9 and thrombospondin-2 increased the sensitivity of detection of PDAC, but slightly reduced specificity. Conclusions Including information on SNPs associated with levels of CA19-9, CEA, and CA-125 can improve the diagnostic accuracy of assays for these tumor markers in the identification of patients with PDAC. Clinicaltrials.gov no: NCT02000089 .
- Published
- 2019
9. In vitro evaluation of a combination treatment involving anticancer agents and an aurora kinase B inhibitor
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Senna Sakai, Yoshifumi Nakayama, Yukiko Yoshiura, Takahiro Yamaguchi, Hiroto Izumi, Yasuo Morimoto, Yoshikazu Harada, Hiroyuki Kurata, and Chiho Koi
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0301 basic medicine ,Cisplatin ,Cancer Research ,Aurora inhibitor ,Articles ,Cell cycle ,Biology ,biology.organism_classification ,Molecular biology ,HeLa ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Doxorubicin ,Aurora Kinase B ,Cytotoxicity ,Etoposide ,medicine.drug - Abstract
Aurora kinase B (AURKB) inhibitors are regarded as potential molecular-targeting drugs for cancer therapy. The present study evaluated the cytotoxic effect of a combination of AZD1152-hQPA, an AURKB inhibitor, and various anticancer agents on the HeLa human cervical cancer cell line, as well as its cisplatin-resistant equivalent HCP4 cell line. It was demonstrated that AZD1152-hQPA had an antagonistic effect on the cytotoxicity of cisplatin, etoposide and doxorubicin, but had a synergistic effect on that of all-trans-retinoic acid (ATRA), Am80 and TAC-101, when tested on HeLa cells. Cisplatin, etoposide and doxorubicin were shown to increase the cellular expression of AURKB, while ATRA, Am80 and TAC-101 downregulated its expression. These results suggested that AURKB expression is regulated by these anticancer agents at the transcriptional level, and that the level of expression of AURKB may influence the cytotoxic effect of AZD1152-hQPA. Therefore, when using anticancer agents, decreasing the expression of AURKB using a molecular-targeting drug may be an optimal therapeutic strategy.
- Published
- 2016
10. The Relationship between Positive Peritoneal Cytology and the Prognosis of Patients with Uterine Cervical Cancer
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Chiho Koi, Seiji Kagami, Toshinori Kawagoe, Yusuke Matsuura, Toru Hachisuga, and Tomoko Kurita
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medicine.medical_specialty ,Time Factors ,Histology ,Multivariate analysis ,Uterine Cervical Neoplasms ,Kaplan-Meier Estimate ,Pathology and Forensic Medicine ,Japan ,Predictive Value of Tests ,Risk Factors ,Cytology ,Odds Ratio ,medicine ,Humans ,Peritoneal Cavity ,Survival rate ,Survival analysis ,Neoplasm Staging ,Proportional Hazards Models ,Retrospective Studies ,Gynecology ,Proportional hazards model ,business.industry ,Carcinoma ,Retrospective cohort study ,General Medicine ,Odds ratio ,Treatment Outcome ,Predictive value of tests ,Multivariate Analysis ,Female ,business - Abstract
Objective: We investigated the association of positive peritoneal cytology with prognosis in uterine cervical cancer. Study Design: We reviewed the medical records and cytologic materials of 225 Japanese patients with FIGO IB1-IVB uterine cervical cancer who had undergone surgery at our University Hospital between 1993 and 2012. Univariate and multivariate regression analyses were performed for statistical analysis. Results: Positive peritoneal cytology was noted in 6 of 225 patients (2.7%). Positive peritoneal cytology was found in 4 of 149 patients (2.6%) with squamous cell carcinoma (SCC) and in 2 of 70 patients (2.8%) with non-SCC (p = 0.9434). The 5-year survival rate of patients with positive peritoneal cytology was significantly lower than that of patients with negative cytology (50 vs. 84.6%, p = 0.001) in univariate survival analysis. However, peritoneal cytology no longer remained significant in multivariate analysis. Conclusion: Although we conclude that positive peritoneal cytology in uterine cervical cancer is a poor prognostic factor, further investigation and multi-institutional studies are necessary.
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- 2015
11. Lovastatin induced Kruppel like factor 2 (
- Author
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Chiho, Koi, Hiroto, Izumi, Tomoko, Kurita, Thuy Thi, Nguyen, Midori, Murakami, Yukiko, Yoshiura, Toru, Hachisuga, and Yasuo, Morimoto
- Subjects
HMG-CoA ,polycyclic compounds ,statin ,nutritional and metabolic diseases ,KLF ,lipids (amino acids, peptides, and proteins) ,RHOB ,cisplatin resistance ,Research Paper - Abstract
It was reported that statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase that are used to prevent hypercholesterolemia, have antitumor activity in several cancers. In this study, we investigated the cell viability of statins in Cisplatin-resistant HCP4 and PCDP5 cells compared with their parent Hela and PC3 cells, respectively, and found that HCP4 and PCDP5 cells were 37-fold and 18-fold more resistant to Cisplatin but 13-fold and 7-fold more sensitive to Lovastatin by cell proliferation assay. Lovastatin induced the apoptosis of HCP4 cells more rapidly and to greater extent than in Hela cells as assessed by flow cytometry and western blotting analyses. The MVA pathway was not involved in this acquired Cisplatin resistance. To elucidate the mechanism underlying the reduced viability to Lovastatin, we performed cDNA microarray analysis and identified 65 and 54 genes that were induced more than 2-fold by Lovastatin in HCP4 and PCDP5 cells, respectively. Of these, only three genes, KLF2, KLF6, and RHOB, were commonly induced between HCP4 and PCDP5 cells. These mRNAs were strongly induced by Lovastatin with transcriptional regulation in HCP4 cells. Consistent with transcription, the protein expression of RHOB also was induced by Lovastatin. The induction of these genes was associated with cell cycle arrest and apoptosis. Combination treatment with Cisplatin and Lovastatin resulted in an agonistic effect in Hela and PC3 cells and an antagonistic effect in HCP4 and PCDP5 cells. These results suggest that statins might have the potential to overcome Cisplatin resistance as single-agent therapy.
- Published
- 2017
12. Expression of N-Acetylgalactosaminyltransferase-6 Is Related to Expression of Cell Adhesion Molecules in Endometrial Cancer
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Chiho Koi, Seiji Kagami, Midori Murakami, Toru Hachisuga, Tomoko Kurita, Hiroto Izumi, and Thuy Nguyen Thi
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0301 basic medicine ,Cancer Research ,Cadherin ,Cell adhesion molecule ,Endometrial cancer ,Cancer ,General Medicine ,Biology ,medicine.disease ,medicine.disease_cause ,Metastasis ,carbohydrates (lipids) ,03 medical and health sciences ,030104 developmental biology ,Oncology ,Cancer cell ,medicine ,Cancer research ,lipids (amino acids, peptides, and proteins) ,Carcinogenesis ,Cell adhesion - Abstract
BACKGROUND The aberrant glycosylation of mucin type O-glycans is thought to be associated with functional alteration of cancer cells, including adhesive properties, as well as their potential for invasion and metastasis. Positive expression of N-acetylgalactosaminyltransferase-6 (GalNAc-T6) may also be a marker for aberrant O-glycans in carcinogenesis. We previously reported that over-expression of GalNAc-T6 had a strong association with endometrial cell invasion ability in vitro. MATERIALS AND METHODS This study investigated the relationship between GalNAc-T6 expression and cell adhesion molecules in 218 endometrial carcinomas by immunohistochemistry. RESULTS Expression of GalNAc-T6 was found to be significantly related to expression of E-cadherin. Positive expression of GalNAc-T6 was significantly associated with better histological grade and good clinical prognosis of patients, but positive E-cadherin and β-catenin expression were not significantly associated with improved overall survival. CONCLUSION GalNAc-T6 might be related to cell-cell adhesion in the early phase of cancer invasion in endometrial carcinoma.
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- 2017
13. Expression of Polypeptide N-Acetylgalactosaminyltransferase-6 in Epithelial Ovarian Carcinoma
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Seiji Kagami, Thuy Thi Nguyen, Midori Murakami, Chiho Koi, Toru Hachisuga, and Tomoko Kurita
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0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,business.industry ,Serous carcinoma ,Polypeptide N-acetylgalactosaminyltransferase ,General Medicine ,Serous Cystadenoma ,medicine.disease ,carbohydrates (lipids) ,03 medical and health sciences ,030104 developmental biology ,Oncology ,Ovarian carcinoma ,parasitic diseases ,Clear cell carcinoma ,Carcinoma ,Medicine ,Mucinous carcinoma ,lipids (amino acids, peptides, and proteins) ,business ,Survival analysis - Abstract
BACKGROUND The family of polypeptide N-acetylgalactosanimyltransferases (GalNAc-Ts) are important factors in glycosylation in carcinomas. The purpose of this study was to investigate the clinical significance of GalNAc-T6 and its correlation with the prognosis of epithelial ovarian carcinoma. MATERIALS AND METHODS A total of 150 patients with epithelial ovarian carcinoma were enrolled and the relationship between GalNAc-T6 expression by immunohistochemistry and long-term survival was evaluated. RESULTS The expression of GalNAc-T6 was positive in 57.6% (34/59) of those with serous carcinoma, 85.3% (29/34) in mucinous carcinoma, 15.6% (5/27) in clear cell carcinoma, and 44% (14/25) in endometrioid carcinoma. In a Kaplan-Meier analysis of patients with grade 1 or 2 serous carcinoma, the 10-year overall survival rates were 47.4% in the GalNAc-T6-positive and 9.1% in the GalNAc-T6-negative groups (p=0.047). CONCLUSION GalNAc-T6 expression in epithelial ovarian carcinoma was different according to pathological type. In low-grade serous carcinoma, GalNAc-T6 expression may contribute to improved long-term survival.
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- 2017
14. Expression of
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Tomoko, Kurita, Thuy Nguyen, Thi, Chiho, Koi, Midori, Murakami, Seiji, Kagami, Hiroto, Izumi, and Toru, Hachisuga
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Gene Expression Regulation, Neoplastic ,Antigens, CD ,Cell Line, Tumor ,Cell Adhesion ,Humans ,N-Acetylgalactosaminyltransferases ,Female ,Neoplasm Grading ,Cadherins ,Prognosis ,Survival Analysis ,beta Catenin ,Endometrial Neoplasms - Abstract
The aberrant glycosylation of mucin type O-glycans is thought to be associated with functional alteration of cancer cells, including adhesive properties, as well as their potential for invasion and metastasis. Positive expression of N-acetylgalactosaminyltransferase-6 (GalNAc-T6) may also be a marker for aberrant O-glycans in carcinogenesis. We previously reported that over-expression of GalNAc-T6 had a strong association with endometrial cell invasion ability in vitro.This study investigated the relationship between GalNAc-T6 expression and cell adhesion molecules in 218 endometrial carcinomas by immunohistochemistry.Expression of GalNAc-T6 was found to be significantly related to expression of E-cadherin. Positive expression of GalNAc-T6 was significantly associated with better histological grade and good clinical prognosis of patients, but positive E-cadherin and β-catenin expression were not significantly associated with improved overall survival.GalNAc-T6 might be related to cell-cell adhesion in the early phase of cancer invasion in endometrial carcinoma.
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- 2017
15. Expression of Polypeptide
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Midori, Murakami, Seiji, Kagami, Thuy Thi, Nguyen, Chiho, Koi, Tomoko, Kurita, and Toru, Hachisuga
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Ovarian Neoplasms ,Cystadenoma, Serous ,Carcinoma, Ovarian Epithelial ,Middle Aged ,Prognosis ,Adenocarcinoma, Mucinous ,Survival Analysis ,Gene Expression Regulation, Neoplastic ,Humans ,N-Acetylgalactosaminyltransferases ,Female ,Neoplasms, Glandular and Epithelial ,Carcinoma, Endometrioid ,Adenocarcinoma, Clear Cell - Abstract
The family of polypeptide N-acetylgalactosanimyltransferases (GalNAc-Ts) are important factors in glycosylation in carcinomas. The purpose of this study was to investigate the clinical significance of GalNAc-T6 and its correlation with the prognosis of epithelial ovarian carcinoma.A total of 150 patients with epithelial ovarian carcinoma were enrolled and the relationship between GalNAc-T6 expression by immunohistochemistry and long-term survival was evaluated.The expression of GalNAc-T6 was positive in 57.6% (34/59) of those with serous carcinoma, 85.3% (29/34) in mucinous carcinoma, 15.6% (5/27) in clear cell carcinoma, and 44% (14/25) in endometrioid carcinoma. In a Kaplan-Meier analysis of patients with grade 1 or 2 serous carcinoma, the 10-year overall survival rates were 47.4% in the GalNAc-T6-positive and 9.1% in the GalNAc-T6-negative groups (p=0.047).GalNAc-T6 expression in epithelial ovarian carcinoma was different according to pathological type. In low-grade serous carcinoma, GalNAc-T6 expression may contribute to improved long-term survival.
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- 2017
16. GalNAc-T6 in the relationship with invasion ability of endometrial carcinomas and prognostic significance
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Thuy Thi, Nguyen, Tomoko, Kurita, Chiho, Koi, Midori, Murakami, Seiji, Kagami, Toru, Hachisuga, Hisaoka, Masanori, Yasuo, Morimoto, and Hiroto, Izumi
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carbohydrates (lipids) ,lipids (amino acids, peptides, and proteins) ,Original Article - Abstract
O-glycosylation in the field of carcinogenesis has been a critical topic of concern for several decades. The abnormal function of enzymes catalyzing the first step of this process, named polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) has been determined to play an important role in cancer development and metastasis. Accordingly, we investigated the expression of GalNAc-T6 in endometrial carcinoma and evaluated the relationship between invasion characteristics and the cellular level of GalNAc-T6. The results suggested that positive GalNAc-T6 expression is significantly associated with histological grade of tumors and myometrial invasion characteristic. In vitro experiments showed that the over expression of GalNAc-T6 had strong association with the decrease of endometrial cell invasiveness. Taken together, our data support the use of GalNAc-T6 as a potential indicator of good prognosis and noninvasive tumor in patients with endometrial carcinoma.
- Published
- 2017
17. A case of ovarian yolk sac tumor associated with endometrioid adenocarcinoma
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Atsuji Matsuyaya, Seiji Kagami, Chiho Koi, Toru Hachisuga, and Tomoko Kurita
- Subjects
medicine.medical_specialty ,endocrine system diseases ,medicine.medical_treatment ,Endometriosis ,Case Report ,Gastroenterology ,chemistry.chemical_compound ,Internal medicine ,medicine ,Gynecology ,Chemotherapy ,Germ cell neoplasm ,business.industry ,Ovarian yolk sac tumor ,Obstetrics and Gynecology ,Combination chemotherapy ,medicine.disease ,Carboplatin ,digestive system diseases ,female genital diseases and pregnancy complications ,Oncology ,Docetaxel ,chemistry ,Alpha-fetoprotein ,embryonic structures ,business ,Endometrioid adenocarcinoma ,human activities ,Ovarian Yolk Sac Tumor ,medicine.drug - Abstract
Ovarian yolk sac tumor (YST) is characterized by endodermal differentiation, and represents approximately 20% of malignant germ cell neoplasms. The age distribution of patients reported with YST ranges from 16 months to 46 years, but most patients are under 30 years of age (Talerman and Vang, 2011). YST is often found admixed with other types of germ cell neoplasm, but YST associated with epithelial ovarian carcinoma is extremely rare (Talerman and Vang, 2011). Unlike pure YST, YST associated with epithelial ovarian carcinoma is reported in elderly patients, and has a poor response to chemotherapy. Here we describe a case of YST associated with endometrioid adenocarcinoma in a postmenopausal woman. Our patient responded favorably to treatment with Docetaxel and Carboplatin combination chemotherapy, and has survived without evidence of relapse for 48 months postoperatively including a long term follow-up program. To the best of our knowledge, this is the first report of YST associated with endometrioid adenocarcinoma with longterm (> 48 months) successful therapy treatment, according to a Medline search of English publications.
- Published
- 2014
- Full Text
- View/download PDF
18. Three Cases of Disorders of Sex Development Treated by Laparoscopic Gonadectomy
- Author
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Tomoko Kurita, Tomoko Sho, Toru Hachisuga, Satoshi Aramaki, Eiji Shibata, Chiho Koi, and Hirohide Inagaki
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,Medicine ,Disorders of sex development ,business ,medicine.disease - Published
- 2013
19. Overexpression of p53 in the endometrial gland in postmenopausal women
- Author
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Midori Murakami, Shohei Shimajiri, Chiho Koi, Yoshihisa Fujino, Thuy Thi Nguyen, Tomoko Kurita, and Toru Hachisuga
- Subjects
Serous Endometrial Intraepithelial Carcinoma ,medicine.drug_class ,Apoptosis ,Andrology ,Endometrium ,medicine ,In Situ Nick-End Labeling ,Humans ,business.industry ,Estrogen Replacement Therapy ,Estrogen Receptor alpha ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Glandular Cell ,Immunohistochemistry ,Endometrial hyperplasia ,Postmenopause ,Ki-67 Antigen ,Terminal deoxynucleotidyl transferase ,Estrogen ,Female ,Tumor Suppressor Protein p53 ,business ,Hormone - Abstract
OBJECTIVE The p53 signature, which (although morphologically unremarkable) displays diffuse and strong p53 nuclear staining, has been proposed to be a precursor of serous endometrial intraepithelial carcinoma. We examined the overexpression of p53 in postmenopausal endometrial glands. METHODS Postmenopausal endometrial tissues of 82 women with benign disease, including 10 hormone users, were evaluated in this study. Tissues with endometrial hyperplasia and/or polyps were excluded based on a histopathologic review. Expressions of estrogen receptor-α, Ki-67, and p53 were immunohistochemically examined. Apoptotic cells were identified using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Overexpression of p53 was categorized as moderate to strong in more than 50% of glandular cell nuclei. RESULTS Focal glandular overexpression of p53 was observed in 1 (9%) of 10 and in 8 (11%) of 72 postmenopausal endometrial tissue specimens in women with and women without a history of hormone use, respectively. Among nonhormone users, the median Ki-67 and apoptotic indices in the postmenopausal endometrial glands of women with and women without overexpression of p53 were 16% and 6% (P = 0.007) and 1% and 1% (P = 0.345), respectively. All postmenopausal endometrial glands were positive for estrogen receptor-α, regardless of the overexpression of p53. The postmenopausal endometrial glands of estrogen users exhibited significantly higher Ki-67 and apoptotic indices than those of nonestrogen users (P = 0.001 and P < 0.001, respectively). CONCLUSIONS Overexpression of p53 may be responsible for the high proliferative activity of postmenopausal endometrial glandular cells associated with conditions of low apoptotic cell death.
- Published
- 2014
20. Overexpression of p53 in the endometrial gland in postmenopausal women.
- Author
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Chiho Koi, Toru Hachisuga, Midori Murakami, Tomoko Kurita, Thuy Thi Nguyen, Shohei Shimajiri, and Yoshihisa Fujino
- Published
- 2015
- Full Text
- View/download PDF
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