Tsuyoshi Iwasaka

Saga University, Сага Япония, Saga, Japan

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Publications (55)134.8 Total impact

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    ABSTRACT: The present study was undertaken to examine the correlation between serum levels of adiponectin isoforms and the risk for endometrial cancer. This retrospective case-control study included 43 Japanese women with endometrial cancer and 62 Japanese women with no history of cancer. Serum levels of total adiponectin and the respective isoforms were determined by enzyme-linked immunosorbent assay. Multivariate logistic regression analysis was performed on the serum levels of total adiponectin and its isoforms, high molecular weight, middle molecular weight, and low molecular weight adiponectins, after adjustment for confounders (age, body mass index, hypertension, and diabetes mellitus). The distribution of body mass index revealed a statistically significant difference between patients and controls (P = 0.001). A statistically significant difference (P < 0.01) was also found in the incidence of diabetes mellitus between the two groups, although there was no significant difference in the incidence of hypertension. In controls, an inverse correlation was observed between body mass index and serum adiponectin levels. However, in patients, an inverse correlation was found only between body mass index and serum middle molecular weight adiponectin level. After adjustment for confounding variables, the factor found to be most closely associated with endometrial cancer was a lower serum level of middle molecular weight adiponectin (adjusted odds ratio 4.89, 95 % confidence interval value 1.25-19.11, P = 0.022). Low serum level of middle molecular weight adiponectin was the only independent risk factor for endometrial cancer suggesting that the application of adiponectin might prevent or decrease the risk for endometrial cancer.
    International Journal of Clinical Oncology 08/2013; · 1.41 Impact Factor
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    ABSTRACT: Pyomyositis is a rare complication of chemotherapy for non-hematological malignancies. A 58-year old woman with endometrial carcinoma, in whom pyomyositis developed during adjuvant chemotherapy, was presented in this report. After initiating empiric antibiotic therapy for febrile neutrocytopenia, screening CT showed multiple abscesses in the lower limbs. Operative drainage of the abscess was effective.
    World Journal of Surgical Oncology 02/2013; 11(1):45. · 1.09 Impact Factor
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    ABSTRACT: BACKGROUND: It has been suggested that micronutrients such as alpha-tocopherol, retinol, lutein, cryptoxanthin, lycopene, and alpha- and beta-carotene may help in the prevention of cervical cancer. Our aim was to investigate whether serum concentrations and/or dietary intake of micronutrients influence the regression or progression of low-grade cervical abnormalities. METHODS: In a prospective cohort study of 391 patients with cervical intraepithelial neoplasia (CIN) grade 1-2 lesions, we measured serum micronutrient concentrations in addition to a self-administered questionnaire about dietary intake. We evaluated the hazard ratio (HR) adjusted for CIN grade, human papillomavirus genotype, total energy intake and smoking status. RESULTS: In non-smoking regression subjects, regression was significantly associated with serum levels of zeaxanthin/lutein (HR 1.25, 0.78-2.01, p = 0.024). This benefit was abolished in current smokers. Regression was inhibited by high serum levels of alpha-tocopherol in smokers (p = 0.042). In progression subjects, a significant protective effect against progression to CIN3 was observed in individuals with a medium level of serum beta-carotene [HR 0.28, 95 % confidence interval (CI) 0.11-0.71, p = 0.007), although any protective effect from a higher level of serum beta-carotene was weaker or abolished (HR 0.52, 95 % CI 0.24-1.13, p = 0.098). Increasing beta-carotene intake did not show a protective effect (HR 2.30, 95 % CI 0.97-5.42, p = 0.058). CONCLUSIONS: Measurements of serum levels of carotenoids suggest that regression is modulated by smoking status. Maintaining a medium serum level of beta-carotene has a protective effect for progression; however, carotene intake is not correlated with serum levels of carotenoids.
    International Journal of Clinical Oncology 10/2012; · 1.41 Impact Factor
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    ABSTRACT: To determine the role of neutralizing antibody generated by human papillomavirus (HPV) infections, baseline levels of serum neutralizing antibodies directed against HPV 16 and cervical HPV DNA were determined in 242 unvaccinated women with low-grade cervical abnormalities, who were then monitored by cytology and colposcopy every 4 months. In women infected with HPV 16 (n = 42), abnormal cytology persisted longer in those positive for HPV 16-specific neutralizing antibodies at baseline (median time to cytological regression: 23.8 vs. 7.2 months). Progression to cervical precancer (cervical intraepithelial neoplasia grade 3) within 5 years occurred only among women carrying HPV 16-specific neutralizing antibodies (P = 0.03, log-rank test). In women infected with types other than HPV 16 (n = 200), detection of HPV 16-specific neutralizing antibodies was not correlated with disease outcome. In conclusion, development of specific neutralizing antibodies following natural HPV 16 infection did not favor a better outcome of low-grade cervical lesions induced by HPV 16 or by other types; rather, detection of neutralizing antibodies generated by current infection may reflect viral persistence and thus help identify those who are at high risk of disease progression.
    Journal of Medical Virology 07/2012; 84(7):1128-34. · 2.37 Impact Factor
  • Satomi Aihara, Tsuyoshi Iwasaka
    Nippon rinsho. Japanese journal of clinical medicine 06/2012; 70 Suppl 4:260-4.
  • Yoshifumi Nakao, Tsuyoshi Iwasaka
    Nippon rinsho. Japanese journal of clinical medicine 06/2012; 70 Suppl 4:303-8.
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    ABSTRACT: The squamous cell carcinoma antigen (SCCA) is widely used as a serological biomarker for various cancers. There are two known SCCA molecules, SCCA1 and SCCA2. We previously found that interleukin-4 or interleukin-13, two related Th2-type cytokines that play an important role in allergic diseases, induce expression of SCCA1 and SCCA2. In this study, we examined whether combined measurements of SCCA1 and SCCA2 are useful for diagnosing atopic dermatitis (AD). We established new enzyme-linked immunosorbent assays (ELISAs) to specifically detect SCCA1 or SCCA2. We applied serum samples from AD patients with food allergies and from cervical cancer patients to these ELISAs. We performed receiver operating characteristic analyses to diagnose AD and to distinguish AD from cervical cancer. Serum concentrations of both SCCA1 and SCCA2 were elevated in AD patients. The serum concentrations of SCCA1 and SCCA2 positively correlated with the clinical severity of AD, showing high specificity (0.86-0.88) and sensitivity (0.86) against control donors. The serum concentrations of SCCA1 and SCCA2 were elevated in cervical cancer patients; however, the SCCA2/SCCA1 ratios clearly distinguished AD patients from cervical cancer patients with high specificity (0.87) and sensitivity (0.87). Expression of SCCA2 was predominant in AD patients, whereas cervical cancer patients showed a predominance of SCCA1. Combined measurements of SCCA1 and SCCA2 are very useful in estimating the severity of allergic diseases, making it possible to distinguish allergic diseases from cancers.
    Annals of Clinical Biochemistry 03/2012; 49(Pt 3):277-84. · 1.92 Impact Factor
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    ABSTRACT: Genetic variations in human leukocyte antigens (HLA) class II regions may influence the risk of cervical cancer by altering the efficiency of the immune responses to human papillomavirus antigens. This prospective study was designed to evaluate the effects of HLA class II alleles on the natural course of cervical precursor lesions. We followed a total of 454 Japanese women with cytological low-grade squamous intraepithelial lesion (LSIL) and histological cervical intraepithelial neoplasia grades 1 to 2 (CIN1-CIN2). Patients were tested for HLA class II alleles and cervical human papillomavirus DNA at the time of entry and then monitored by cytology and colposcopy every 4 months for a mean follow-up of 39.0 months. We analyzed cumulative probabilities of cytological regression to at least 2 consecutive negative Papanicolaou tests and histological progression to biopsy-positive CIN3. During the follow-up period, 39 lesions progressed to CIN3, and 282 lesions regressed to normal cytology. Progression to CIN3 did not occur in DRB1*1302-positive women, and this protective effect of DRB1*1302 was statistically significant (P = 0.03). Low-grade squamous intraepithelial lesion regressed to normal cytology more quickly in DRB1*1302-positive women than in DRB1*1302-negative women (median time, 8.9 months vs 14.2 months), although the difference was not statistically significant (P = 0.16). The risk of LSIL persistence or progression to CIN3 within 5 years was not affected by any other HLA class II alleles. By using a prospective study design, we demonstrated the protective effect of the DRB1*1302 allele against progression to CIN3 among Japanese women with LSIL.
    International Journal of Gynecological Cancer 03/2012; 22(3):471-8. · 1.94 Impact Factor
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    ABSTRACT: To investigate the natural course of low-grade squamous intraepithelial lesions (LSILs) that cannot be histologically confirmed by colposcopy-directed biopsy. In a multicenter, prospective, cohort study of Japanese women with LSILs, we analyzed the follow-up data from 64 women who had a negative biopsy result at the initial colposcopy (biopsy-negative LSIL) in comparison with those from 479 women who had a histologic diagnosis of cervical intraepithelial neoplasia grade 1 (LSIL/CIN1). Patients were monitored by cytology and colposcopy every 4 months for a mean follow-up period of 39.0 months, with cytologic regression defined as two consecutive negative smears and normal colposcopy. In women with biopsy-negative LSILs, there were no cases of CIN3 or worse (CIN3+) diagnosed within 2 years; the difference in the 2-year risk of CIN3+ between the two groups was marginally significant (0 vs. 5.5%; P = 0.07). The cumulative probability of cytologic regression within 12 months was much higher in the biopsy-negative LSIL group (71.2 vs. 48.6%; P = 0.0001). The percentage of women positive for high-risk human papillomaviruses (hrHPVs) was significantly lower in the biopsy-negative LSIL group than in the LSIL/CIN1 group (62.1 vs. 78.4%; P = 0.01); however, the 12-month regression rate of biopsy-negative LSIL was similar between hrHPV-positive and -negative women (67.3 vs. 74.4%, P = 0.73). In women with biopsy-negative LSILs, the risk of CIN3+ diagnosed within 2 years was low; furthermore, approximately 70% underwent cytologic regression within 12 months, regardless of HPV testing results. Biopsy-negative LSILs may represent regressing lesions rather than lesions missed by colposcopy.
    International Journal of Clinical Oncology 07/2011; 17(3):233-9. · 1.41 Impact Factor
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    ABSTRACT: Only a subset of cervical precursor lesions progress to cervical cancer and because of the lack of the predictive markers, it cannot be ascertained which lesions will progress or not. To estimate the risk of disease progression associated with human papillomavirus (HPV) genotypes, we followed 570 Japanese women with cytological LSIL (low-grade squamous intraepithelial lesion) and histological CIN (cervical intraepithelial neoplasia) grade 1-2 lesions (479 CIN 1; 91 CIN 2) at 3 to 4 month intervals for a mean follow-up period of 39.1 months. At entry, we detected HPV DNA in cervical samples by polymerase chain reaction-based methodology. Over the period of follow-up period, 46 lesions progressed to CIN 3 while 362 regressed to normal cytology. Women with multiple HPV infections were more likely to have persistent lesions (hazard ratio [HR] for regression, 0.65; 95% confidence interval [CI], 0.42-1.02; p = 0.07); however, multiple infections did not increase the risk of progression (HR for progression, 1.04; 95% CI, 0.37-2.94; p = 0.94). After adjusting for CIN grade and women's age, HRs for progression to CIN 3 (vs. women with low-risk types or negative for HPV DNA) varied markedly by HPV genotype: type 16 (11.1, 95% CI: 1.39-88.3); 18 (14.1, 0.65-306); 31 (24.7, 2.51-243); 33 (20.3, 1.78-231); 35 (13.7, 0.75-251); 52 (11.6, 1.45-93.3); 58 (8.85, 1.01-77.6); other high-risk types (4.04, 0.47-34.7). HPV 45 was not detected in our study subjects. The cumulative probability of CIN 3 within 5 years was 20.5% for HPV 16, 18, 31, 33, 35, 52 and 58; 6.0% for other high-risk types; 1.7% for low-risk types (p = 0.0001). In conclusion, type-specific HPV testing for women with LSIL/CIN 1-2 lesions is useful for identifying populations at increased or decreased risk of disease progression.
    International Journal of Cancer 06/2011; 128(12):2898-910. · 6.20 Impact Factor
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    ABSTRACT: Tuberous sclerosis complex (TSC) is associated with benign and malignant tumors, including lymphangioleiomyomatosis (LAM) and angiomyolipoma (AML). We herein describe the TSC case of a 50-year-old woman having a papillary serous carcinoma of the peritoneum (PSCP), LAM, and AML. On microscopic examination, the PSCP cells showed a cuboidal to columnar shape, proliferated into the papillae, and infiltrated into the peritoneal cavity and anterior thoracic wall. On immunohistochemical evaluation, the tumor cells were positive for epithelial membrane antigen, human epidermal cytokeratins, and progesterone receptor, but negative for calretinin, carcinoembryonic antigen, MCF-7 cell line (Ber-EP4), and estrogen receptor.
    Case reports in pathology. 01/2011; 2011:564260.
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    ABSTRACT: Endometrial carcinoma is one of the most common gynecologic malignancies in Japan and its incidence has increased recently. Although surgery is the cornerstone of the management of patients with endometrial cancer, there is significant variation in Japan with regard to the type of hysterectomy employed. Additionally, it remains controversial whether full nodal staging is required in all patients. Furthermore, adjuvant therapy differs between Japan and Western countries. To delineate clearly the standard of care for endometrial cancer treatment in Japan, the guidelines for the treatment of endometrial cancer were published in 2006 and revised in 2009. The 2009 edition included topics not addressed in the previous edition including the treatment of mesenchymal tumors, for example leiomyosarcoma, and sections covering the treatment of serous and clear-cell adenocarcinoma. These guidelines are composed of nine chapters and include nine algorithms. The guidelines also contain fifty-one clinical questions (CQs) and each CQ consists of recommendations, background, explanations, and references. The treatment recommendations herein are tailored to reflect current Japanese clinical practice and ensure equitable care for all Japanese women diagnosed with endometrial cancer.
    International Journal of Clinical Oncology 11/2010; 15(6):531-42. · 1.41 Impact Factor
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    ABSTRACT: The role of tobacco smoking in the multistage carcinogenesis at the cervix is not fully understood because of a paucity of prospective data. To assess the relationship between smoking and spontaneous regression of cervical precursor lesions, a total of 516 women with low-grade squamous intraepithelial lesion (LSIL) were monitored by cytology and colposcopy every 4 months. Probability of LSIL regression within 2 years was analyzed in relation to smoking behaviors, with regression defined as at least two consecutive negative Pap smears and normal colposcopy. Women's age, initial biopsy results, and human papillomavirus (HPV) genotypes were included in the multivariate models for adjustments. Our study subjects included 258 never-smokers and 258 smokers (179 current and 79 former smokers). During a mean follow-up time of 39.8 months, 320 lesions regressed to normal cytology. Probability of regression within 2 years was significantly lower in smokers than in never-smokers (55.0%vs 68.8%, P = 0.004). The risk of LSIL persistence increased with smoking intensity and duration and with younger age at starting smoking (P = 0.003, P < 0.001, and P = 0.03, respectively). Smokers had twice as high a risk of persistent HPV infection compared to never-smokers (odds ratio, 2.50; 95% confidence interval, 1.30-4.81; P = 0.006). In young women, passive smoking since childhood reduced probability of regression within 2 years (56.7%vs 85.9%, P < 0.001). Further adjustments for a wide range of cervical cancer risk factors did not change the findings. In conclusion, tobacco smoking may interfere with regression of cervical precursor lesions. Childhood exposure to second-hand smoke may increase a risk of persistent cervical abnormalities among young women.
    Cancer Science 09/2010; 101(9):2065-73. · 3.48 Impact Factor
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    ABSTRACT: We examined corpus cancer to identify whether there are distinctive patterns of global gene expression and microsatellite instability, and to gain molecular understanding of its carcinogenesis and progression. Thirty endometrioid corpus cancer tissue samples (21 of G1 and nine of G2/3) were analyzed by cDNA microarray based on 637 cancer-associated genes and by a polymerase chain reaction method for microsatellite instability. Of the 30 cases, 10 (33%) were recognized as having microsatellite instability. In all cases, four genes were overexpressed and five genes were underexpressed. There were six microsatellite instability-specific overexpressed or high-frequency genes and 15 underexpressed or low-frequency genes. Furthermore, we identified several genes by grade analysis. These results may be useful resources for the development of diagnostic assays, prognostic factors, or therapeutic targets for corpus endometrioid cancer.
    Journal of Obstetrics and Gynaecology Research 04/2010; 36(2):336-43. · 0.84 Impact Factor
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    ABSTRACT: Clinical practice guidelines for gynecologic cancers have been published by the National Comprehensive Cancer Network and the National Cancer Institute. Whereas these guidelines form the basis for the standard of care for gynecologic malignancies in the United States, it has proven difficult to institute them in Japan due to differences in patient characteristics, health-care delivery systems, and insurance programs. Therefore, evidence-based guidelines for treating cervical cancer specifically in Japan have been under development. The Guidelines Formulation Committee and Evaluation Committee were independently established within the Committee for Treatment Guidelines for Cervical Cancer. Opinions from within and outside the Japan Society of Gynecologic Oncology (JSGO) were incorporated into the final draft, and the guidelines were published after approval by the JSGO. These guidelines are composed of ten chapters and comprise three algorithms. Each chapter consists of a clinical question, recommendations, background, objectives, explanations, and references. The objective of these guidelines is to clearly delineate the standard of care for cervical cancer treatment in Japan in order to ensure equitable care for all Japanese women diagnosed with cervical cancer.
    International Journal of Clinical Oncology 03/2010; 15(2):117-24. · 1.41 Impact Factor
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    ABSTRACT: To assess the safety and efficacy of neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for müllerian carcinomas, such as ovarian, tubal, and peritoneal cancers, and to determine whether we can omit diagnostic laparoscopy before treatment initiation, a feasibility study was performed. Eligible patients had presumed stage III/IV müllerian carcinomas clinically diagnosed by imaging studies, cytology, and tumor markers. All patients underwent diagnostic laparoscopy to confirm the clinical diagnosis. Four cycles of paclitaxel and carboplatin were administered as NAC, followed by interval debulking surgery and an additional 4 cycles of chemotherapy. The primary end point was the proportion of patients achieving clinical complete remission (cCR) among all stage III/IV müllerian carcinomas confirmed by diagnostic laparoscopy. The major secondary end point was the positive predictive value (PPV) of clinical diagnosis. Fifty-six patients were enrolled into the study. The PPV of overall clinical diagnosis for the tumor origin, histology, and stage was 95% (53/56). Fifty-three patients received the protocol treatment starting with NAC. IDS was performed in 89% (47/53) of patients. Complete resection without residual tumors was achieved in 55% (29/53) and residual tumors became <1 cm in 17% (9/53) of patients. Twenty-two patients (42%) achieved cCR after completion of the treatment. The median overall and progression-free survival was 45 and 14 months, respectively. NAC without diagnostic laparoscopy for advanced müllerian carcinomas holds sufficient promise to be compared with direct surgery in a phase III trial.
    Gynecologic Oncology 01/2009; 113(1):57-62. · 3.93 Impact Factor
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    ABSTRACT: To investigate the combined effect of the major tea polyphenol, (-)-epigallocatechin gallate (EGCG) and retinoic acid (RA) on cervical adenocarcinoma. Cell growth rate was examined after treatment for 4, 7 and 10 days with 0-100 microM EGCG and/or 1 microM RA in two cervical adenocarcinoma cell lines, HeLa and TMCC-1. The effect of EGCG treatment was examined for the induction of apoptosis by DNA ladder assay and caspase-3-related protease activity in cell lysate. Telomerase activity was detected by stretch PCR telomere extension assay. hTERT expression levels were quantified by a real-time PCR system. Combining EGCG and RA increased the antiproliferative effect in adenocarcinoma cell lines, whereas EGCG or RA treatment alone caused a less sensitive response in these cells. Neither EGCG nor RA treatment alone affected apoptosis and telomerase activity. The combination treatment of EGCG and RA induced apoptosis and inhibited telomerase activity in adenocarcinoma cell lines. These results were consistent with those of an antiproliferative effect of EGCG and/or RA in cervical adenocarcinoma cells. Our data suggest that EGCG and RA combined to prevent the carcinogenesis of cervical adenocarcinoma, induce apoptosis and inhibit telomerase activity. The treatments of combining EGCG and RA may be effective in preventing or treating cervical adenocarcinoma.
    Gynecologic Oncology 03/2008; 108(2):326-31. · 3.93 Impact Factor
  • Yoshifumi Nakao, Masatoshi Yokoyama, Tsuyoshi Iwasaka
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    ABSTRACT: Cervical pregnancy can be a life-threatening condition due to the risk of severe hemorrhage. Progression of ultrasonographic diagnostic technology has allowed the early detection of cervical pregnancy. However, a standard treatment protocol for fertility preservation has not yet been established. Two women with cervical pregnancy presented with cardiac activity at 6 and 7 weeks of gestation. They were treated with transfemoral uterine artery embolization followed by dilation and curettage with minimal bleeding. One patient gave birth to a healthy neonate 20 months after the procedure. Early cervical pregnancies were treated with dilation and curettage after uterine artery embolization. This treatment can be considered as conservative management for patients who desire to preserve their fertility.
    Obstetrics and Gynecology 03/2008; 111(2 Pt 2):505-7. · 4.80 Impact Factor
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    ABSTRACT: To assess the efficacy of fertility-sparing treatment using medroxyprogesterone acetate (MPA) for endometrial carcinoma (EC) and atypical endometrial hyperplasia (AH) in young women. This multicenter prospective study was carried out at 16 institutions in Japan. Twenty-eight patients having EC at presumed stage IA and 17 patients with AH at younger than 40 years of age were enrolled. All patients were given a daily oral dose of 600 mg of MPA with low-dose aspirin. This treatment continued for 26 weeks, as long as the patients responded. Histologic change of endometrial tissue was assessed at 8 and 16 weeks of treatment. Either estrogen-progestin therapy or fertility treatment was provided for the responders after MPA therapy. The primary end point was a pathologic complete response (CR) rate. Toxicity, pregnancy rate, and progression-free interval were secondary end points. CR was found in 55% of EC cases and 82% of AH cases. The overall CR rate was 67%. Neither therapeutic death nor irreversible toxicities were observed; however, two patients had grade 3 body weight gain, and one patient had grade 3 liver dysfunction. During the 3-year follow-up period, 12 pregnancies and seven normal deliveries were achieved after MPA therapy. Fourteen recurrences were found in 30 patients (47%) between 7 and 36 months. The efficacy of fertility-sparing treatment with a high-dose of MPA for EC and AH was proven by this prospective trial. Even in responders, however, close follow-up is required because of the substantial rate of recurrence.
    Journal of Clinical Oncology 08/2007; 25(19):2798-803. · 18.04 Impact Factor
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    ABSTRACT: To elucidate the silencing mechanism of retinoic acid receptor beta2 (RAR beta2) in cervical carcinogenesis, we investigated RAR beta2 expression and the status of both DNA methylation and histone modifications at the promoter in cervical cancer cell lines. RAR beta2 was frequently repressed in cancer cell lines and in primary cancers of the cervix. Although the majority of RAR beta2-negative cancers had methylated promoter, RAR beta2 was repressed with hypomethylated promoter in a substantial fraction of the cancers. The RAR beta2-negative cells with hypomethylated promoters showed a repressive histone modification pattern at the promoter. RAR beta2 was reactivated by a histone deacetylase inhibitor, accompanied by formation of active histone modifications. The repressive modification was also observed in cells repressed with hypermethylated promoter, but RAR beta2 was reactivated only by DNA demethylating agent and not by histone deacetylase inhibitor. Our results suggest that RAR beta2 is silenced by either of the two key epigenetic pathways, DNA methylation or repressive histone modifications, depending on the individual cancer cells.
    Cancer Letters 04/2007; 247(2):318-27. · 4.26 Impact Factor

Publication Stats

617 Citations
134.80 Total Impact Points


  • 2004–2013
    • Saga University
      • Division of Obstetrics & Gynecology
      Сага Япония, Saga, Japan
  • 2012
    • Keio University
      • Department of Obstetrics and Gynecology
      Tokyo, Tokyo-to, Japan
  • 2010–2012
    • University of Tsukuba
      • Institute of Clinical Medicine
      Tsukuba, Ibaraki, Japan
    • Sasaki Foundation
      Edo, Tōkyō, Japan
  • 2009
    • National Cancer Center
      • Center for Cancer Control and Information Services
      Tokyo, Tokyo-to, Japan
  • 1997
    • Memorial University of Newfoundland
      • Faculty of Medicine
      Saint John, New Brunswick, Canada