Decreased ARID1A expression is correlated with chemoresistance in epithelial ovarian cancer

Yoshihito Yokoyama,Yoko Matsushita,Tatsuhiko Shigeto,Masayuki Futagami,Hideki Mizunuma 대한부인종양학회 2014 Journal of Gynecologic Oncology Vol.25 No.1

Objective: Loss of ARID1A is related to oncogenic transformation of ovarian clear cell adenocarcinoma. The present study was conducted in epithelial ovarian cancer of all tissue types to investigate whether an increased or decreased expression level of ARID1A can be a prognostic factor for ovarian cancer or can influence the sensitivity to anticancer drugs. Methods: The expression level of ARID1A was investigated in 111 patients with epithelial ovarian cancer who received initial treatment at the Hirosaki University Hospital between 2006 and 2011. The expression level of ARID1A was immunohistochemically graded using staining scores, which were calculated by multiplying the staining intensity of the nuclei by the stain-positive area. Results: The level of ARID1A was significantly lower in clear cell adenocarcinoma than in other histologic types. Among the patients with stage III, IV cancer (n=46), the level of ARID1A was significantly lower (p=0.026) in patients who did not achieve complete response (CR; n=12) than in patients who achieved CR (n=34). The level of ARID1A was relatively lower (p=0.07) in patients who relapsed after achieving CR (n=21) than in patients who did not relapse (n=13). When the staining score of 0 was defined as ARID1A-negative and other staining scores were defined as ARID1A-positive, there was significant difference in progression-free survival between ARID1A-negative (n=11) and ARID1A-positive (n=35) patients in stage III, IV disease. Conclusion: The result suggests that decreased ARID1A expression is correlated with chemoresistance and may be a predictive factor for the risk of relapse of advanced cancer after achieving CR.

Original Article : Adsorptive Granulocyte/Monocyte Apheresis for the Maintenance of Remission in Patients with Ulcerative Colitis: A Prospective Randomized, Double Blind, Sham-Controlled Clinical Trial

( Ken Fukunaga ),( Yoko Yokoyama ),( Koji Kamokozuru ),( Kazuko Nagase ),( Shiro Nakamura ),( Hiroto Miwa ),( Takayuki Matsumoto ) The Editorial Office of Gut and Liver 2012 Gut and Liver Vol.6 No.4

Background/Aims: Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse. Methods: Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy. They were then randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal circulation without the GMA column every 4 weeks (Sham, n=11), or no additional intervention (Control, n=11). The primary endpoint was the rate of avoiding relapse (AR) over 48 weeks. Results: At week 48, the AR rates in the True, Sham, and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were steroid- free, but no statistically significant difference was seen among the three arms. However, in patients who could taper their prednisolone dose to <20 mg/day during the remission induction therapy, the AR in the True group was better than in the Sham (p<0.03) or Control (p<0.05) groups. Conclusions: Monthly GMA may potentially prevent UC relapse in patients who have achieved remission through weekly GMA, especially in patients on <20 mg/day PSL at the start of the maintenance therapy. (Gut Liver 2012;6:427-433)

Assessment of Therapeutic Effect of Sunitinib by $^{11}C$-Acetate PET Compared with FDG PET Imaging in a Patient with Metastatic Renal Cell Carcinoma

Oyama, Nobuyuki,Takahara, Noriko,Hasegawa, Yoko,Tanase, Kazuya,Miwa, Yoshiji,Akino, Hironobu,Okazawa, Hidehiko,Kudo, Takashi,Fujibayashi, Yasuhisa,Yokoyama, Osamu The Korea Society of Nuclear Medicine 2011 핵의학 분자영상 Vol.45 No.3

Although sunitinib shows a high response rate in patients with untreated metastatic renal cell carcinoma (mRCC), quite a few patients show no therapeutic effect. Therefore, it is crucial to distinguish the patients who respond to sunitinib from those who do not as early as possible after the administration of the therapy. We herein report a case of mRCC in which $^{11}C$-acetate (AC) positron emission tomography (PET) showed an early therapeutic effect of sunitinib treatment 4 weeks after its administration.

NUDT15, FTO, and RUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases

( Toshiyuki Sato ),( Tetsuya Takagawa ),( Yoichi Kakuta ),( Akihiro Nishio ),( Mikio Kawai ),( Koji Kamikozuru ),( Yoko Yokoyama ),( Yuko Kita ),( Takako Miyazaki ),( Masaki Iimuro ),( Nobuyuki Hida ) 대한장연구학회 2017 Intestinal Research Vol.15 No.3

Background/Aims: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD). Methods: One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing. Results: None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined. Conclusions: Of the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurineinduced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD. (Intest Res 2017;15:328-337)

Prevalence of Irritable Bowel Syndrome-like Symptoms in Japanese Patients with Inactive Inflammatory Bowel Disease

( Toshihiko Tomita ),( Yu Kato ),( Mayu Takimoto ),( Takahisa Yamasaki ),( Takashi Kondo ),( Tomoaki Kono ),( Katsuyuki Tozawa ),( Yoko Yokoyama ),( Hisatomo Ikehara ),( Yoshio Ohda ),( Tadayuki Oshim 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.4

Background/Aims Few studies are available that have investigated the risk factors for overlapping irritable bowel syndrome (IBS)-like symptoms in patients with inactive inflammatory bowel disease (IBD). The present study has 3 objectives: (1) to assess the prevalence of IBS-like symptoms in Japanese patients with inactive IBD using Rome III criteria, (2) to examine the relationship of IBS-like symptoms to health related quality of life (HR-QOL), and (3) to investigate associations for developing IBS-like symptoms in patients with inactive IBD. Methods IBS-like symptoms were evaluated using the Rome III questionnaire for functional gastrointestinal disorders. HR-QOL and hospital anxiety and depression scale were evaluated. Results IBS-like symptoms were found in 17.5% (7/40) of patients with inactive ulcerative colitis, 27.1% (29/107) of patients with inactive Crohn’s disease (CD), and 5.3% (23/438) of healthy control subjects. The QOL level was significantly lower and anxiety score was significantly higher in inactive CD patients with IBS-like symptoms than in those without such symptoms (P = 0.003, P = 0.009). Use of anti-anxiety drugs was associated with the presence of IBS symptoms (P = 0.045). HR-QOL score was lower and anxiety score was higher in patients with inactive ulcerative colitis, but the difference was not statistically significant. Conclusions The prevalence of IBS-like symptoms in inactive IBD patients was significantly higher than in healthy controls. Inactive CD patients with IBS-like symptoms has low QOL and anxiety; suggesting that anxiety may be associated with symptom development in such patients.

Infl iximab Therapy Impacts the Peripheral Immune System of Immunomodulator and Corticosteroid Naïve Patients with Crohn’s Disease

Kyoichi Kato,Ken Fukunaga,Koji Kamikozuru,Shinichiro Kashiwamura,Nobuyuki Hida,Yoshio Ohda,Naohisa Takeda,Koji Yoshida,Masaki Iimuro,Yoko Yokoyama,Risa Kikuyama,Hiroto Miwa,Takayuki Matsumoto 거트앤리버 소화기연관학회협의회 2011 Gut and Liver Vol.5 No.1

Background/Aims: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-α has effi cacy in treating Crohn’s disease (CD). However, knowledge of the potential effects of IFX on patients’ immune profi les is lacking. The purpose of this study was to reveal the immunological effects of IFX. Methods: Twenty-two patients with a CD activity index (CDAI)of 194.2±92.9 and an average duration of disease of 3.26months and 21 healthy controls were included. Patients were to have their fi rst IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. Results:CDAI signifi cantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13(p<0.01), transforming growth factor-β1 (p<0.01), and ‘regulated on activation, normal T cell expressed and secreted’(RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-α (p<0.04), IL-6 (p<0.03), interferon (IFN)-γ(p<0.04), IFN-γ-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage infl ammatory protein-1β (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01)and a decrease in the Th1 (IFN-γ)/Th2 (IL-4) ratio (p<0.03). Conclusions: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naïve Th0 lymphocytes to Treg. This knowledge should have clinical relevance.

Infl iximab Therapy Impacts the Peripheral Immune System of Immunomodulator and Corticosteroid Naive Patients with Crohn`s Disease

( Kyoichi Kato ),( Ken Fukunaga ),( Koji Kamikozuru ),( Shinichiro Kashiwamura ),( Nobuyuki Hida ),( Yoshio Ohda ),( Naohisa Takeda ),( Koji Yoshida ),( Masaki Iimuro ),( Yoko Yokoyama ),( Risa Kikuya 대한소화기기능성질환·운동학회 2011 Gut and Liver Vol.5 No.1

Background/Aims: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-α has effi cacy in treating Crohn`s disease (CD). However, knowledge of the potential effects of IFX on patients` immune profi les is lacking. The purpose of this study was to reveal the immunological effects of IFX. Methods: Twenty-two patients with a CD activity index (CDAI) of 194.2±92.9 and an average duration of disease of 3.26 months and 21 healthy controls were included. Patients were to have their fi rst IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/ CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. Results: CDAI signifi cantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13 (p<0.01), transforming growth factor-β1 (p<0.01), and ``regulated on activation, normal T cell expressed and secreted`` (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-α (p<0.04), IL-6 (p<0.03), interferon (IFN)-γ (p<0.04), IFN-γ-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage infl ammatory protein-1β (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01) and a decrease in the Th1 (IFN-γ)/Th2 (IL-4) ratio (p<0.03). Conclusions: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naive Th0 lymphocytes to Treg. This knowledge should have clinical relevance. (Gut Liver 2011;5:37-45)