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  • Wiley  (2)
  • Choi, Ilseung  (2)
  • Ishida, Takashi  (2)
  • Narita, Tomoko  (2)
  • Suzuki, Susumu  (2)
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  • Wiley  (2)
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  • 1
    In: Cancer Science, Wiley, Vol. 109, No. 1 ( 2018-01), p. 74-83
    Abstract: Indoleamine 2,3‐dioxygenase 1 (IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway. The purpose of the present study was to determine the clinical significance of Trp catabolism in newly diagnosed Hodgkin lymphoma (HL) patients. We quantified serum Trp and Kyn in 52 HL patients, and analyzed their associations with different clinical parameters including serum soluble CD30 concentration. The IDO expression was evaluated in the patients’ affected lymph nodes. The cohort comprised 22 male and 30 female patients (age range, 15‐81 years; median, 45 years), with a 5‐year overall survival (OS) of 88.6%. The OS was significantly shorter for patients with a high Kyn/Trp ratio (OS at 5 years, 60.0% vs 92.2%), for those with stage IV disease, and for those with lymphocytopenia ( 〈 600/mm 3 and/or 〈 8% white blood cell count). The latter two parameters are components of the international prognostic score for advanced HL. In contrast, there were no significant differences in OS according to age, serum albumin, hemoglobin, sex, white blood cell count, or serum soluble CD30 (≥ or 〈 285.6 ng/mL). Multivariate analysis using the three variables stage, lymphocytopenia, and serum Kyn/Trp ratio showed that only the latter significantly affected OS. Indoleamine 2,3‐dioxygenase 1 was produced by macrophages/dendritic cells, but not by HL tumor cells, and IDO levels determined by immunohistochemistry had a significant positive correlation with the serum Kyn/Trp ratio. In conclusion, quantification of serum Kyn and Trp is useful for predicting prognosis of individual HL patients.
    Type of Medium: Online Resource
    ISSN: 1347-9032 , 1349-7006
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2115647-5
    detail.hit.zdb_id: 2111204-6
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  • 2
    In: Hematological Oncology, Wiley, Vol. 38, No. 5 ( 2020-12), p. 742-753
    Abstract: The enzyme, indoleamine 2,3‐dioxygenase 1 (IDO), catabolizes tryptophan (Trp) in the kynurenine (Kyn) pathway, and is important in suppressing antitumor immune responses in the tumor microenvironment. With regard to previously untreated patients with follicular lymphoma (FL), we sought to establish the prognostic significance of Trp catabolism in this disease. Serum Trp and Kyn levels in 110 patients with FL were quantified, and their relationship to different clinical parameters studied. IDO expression in the lymph nodes of affected patients was studied. Study participants included 54 males and 56 females (age range 39–86, median 62 years), showing a 5‐year overall survival (OS) rate of 78.5%. Patients with a high Kyn level (5‐year OS, 65.0% vs. 81.7%; p  = 0.026), high Kyn/Trp ratio (71.1% vs. 81.7%; p  = 0.002), and low hemoglobin (Hb) level ( 〈 12.0 g/dL; p  = 0.001; a component of FL international prognostic indexes) demonstrated a significantly shorter OS. Multivariate analysis included the following 10 variables: age, sex, serum β2‐microglobulin, Hb, longest diameter of the largest involved node, Ann Arbor stage, serum lactate dehydrogenase, histologic grading, B symptoms, and serum Kyn/Trp ratio; a lower Hb level and a high Kyn/Trp ratio (HR, 3.239; 95% CI, 1.296–8.096) led to a significantly inferior OS. In the microenvironment, some CD11c‐positive myeloid dendritic cells but not FL tumor cells were found to produce IDO. Overall, measuring levels of serum Kyn and Trp in individual patients with FL contributed to predicting their prognosis.
    Type of Medium: Online Resource
    ISSN: 0278-0232 , 1099-1069
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2001443-0
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