Development of the novel diagnostic and treatment strategies targeting at Epithelial to mesenchymal transition related transcription factors in primary central nervous system lymphomas
| Project/Area Number |
17K10870
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurosurgery
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
MAKINO KEISHI 熊本大学, 病院, 非常勤診療医師 (90381011)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
中村 英夫 久留米大学, 医学部, 准教授 (30359963)
大塚 雅巳 熊本大学, 大学院生命科学研究部(薬), 客員教授 (40126008)
秀 拓一郎 北里大学, 医学部, 准教授 (40421820)
篠島 直樹 熊本大学, 病院, 講師 (50648269)
黒田 順一郎 熊本大学, 大学院生命科学研究部(医), 助教 (90536731)
|
|---|
| Project Period (FY) |
2017-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | 脳原発悪性リンパ腫 / 治療抵抗性 / 転移、浸潤能 / 治療標的分子 / 上皮ー間葉転換誘導因子 / 悪性脳腫瘍 / 上衣腫 / 浸潤 / 放射線治療 / 晩期障害 / 上皮間葉転換 / 脳腫瘍 / 上皮間葉転換因子 / 新規治療開発 / 予後因子 / MYCタンパク / BCL2タンパク / 脳悪性リンパ腫 / 上皮ー間葉転換 / バイオマーカー / 治療開発 |
|---|
| Outline of Final Research Achievements |
Histological and immunohistochemical testing were performed to evaluate the patients’ statuses for various markers {Epithelial-to-mesenchymal transition (EMT) related transcription factors (ZEB1 and Slug) , MYC and BCL2}, which were also evaluated for associations with survival outcomes in primary central nervous system lymphoma (PCNSL). Higher expression of ZEB1 and Slug was found in the cases with CNS lymphomas. These expressions were significantly shown in case with multiple tumors. Furthermore, positivity of active form of Slug was associated with both poor overall and progression-free survival. Additionally, BCL2 positivity was significantly associated with poor overall survival and progression-free survival. These data suggested that evaluating Slug and BCL2 might help predict the prognosis in cases of PCNSL. Furthermore, these molecules might be novel therapeutic targets.
|
| Academic Significance and Societal Importance of the Research Achievements |
脳原発悪性リンパ腫は、近年免疫抑制患者以外の一般人口においても急激な発生増加が認められ、注目を集めている。臨床的な特徴としては、比較的高齢者に発生する傾向にある、急速に症状が進行する、頭蓋内の数カ所に同時に多発する例もある、高度の認知機能障害を生じるなどが挙げられる。予後や治療反応性を予測できるバイオマーカーの確立は、個別化した最適な治療を計画するうえで重要である。本研究の結果から、上皮―間葉転換誘導因子(Slug)の発現は、予後、腫瘍の多発性と関連しており、また細胞死の抑制に関連するBCL2の発現も予後に関連していたので、脳原発悪性リンパ腫において有力なバイオマーカー候補と考えられる。
|
Report
(5 results)
Research Products
(26 results)
-
-
-
-
[Journal Article] Machine learning based on multi-parametric magnetic resonance imaging to differentiate glioblastoma multiforme from primary cerebral nervous system lymphoma.2018
Author(s)
Nakagawa M, Nakaura T, Namimoto T, Kitajima M, Uetani H, Tateishi M, Oda S, Utsunomiya D, Makino K, Nakamura H, Mukasa A, Hirai T, Yamashita Y
-
Journal Title
European journal of radiology
Volume: 108
Pages: 147-154
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] CSF TACI and BAFF levels in patients with primary CNS lymphoma as novel diagnostic biomarkers.2018
Author(s)
Mizutani H, Nakane S, Ikeda T, Nakamura H, Takamatsu K, Makino K, Tawara N, Mukaino A, Watari M, Matsui H, Mukasa A, Ando Y
-
Journal Title
Annals of clinical and translational neurology
Volume: 5
Issue: 12
Pages: 1611-1616
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Additive Value of 3T 3D CISS Imaging to Conventional MRI for Assessing the Abnormal Vessels of Spinal Dural Arteriovenous Fistulae2018
Author(s)
Uetani H, Hirai T, Kitajima M, Azuma M, Yano S, Nakamura H, Makino K, Kai Y, Nagayama Y, Kadota Y, Yamashita Y
-
Journal Title
Magnetic Resonance in Medical Sciences
Volume: 17
Issue: 3
Pages: 218-222
DOI
NAID
ISSN
1347-3182, 1880-2206
Related Report
-
[Journal Article] A nationwide multi-institutional retrospective study to identify prognostic factors and develop a graded prognostic assessment system for patients with brain metastases from uterine corpus and cervical cancer.2017
Author(s)
Hayashi N, Takahashi H, Hasegawa Y, Higuchi F, Takahashi M, Makino K, Takagaki M, Akimoto J, Okuda T, Okita Y, Mitsuya K, Hirashima Y, Narita Y,Nakasu Y
-
Journal Title
BMC Cancer
Volume: 17
Issue: 1
Pages: 397-397
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Monocyte chemoattractant protein 1 expression and proliferation in primary central nervous system lymphoma2017
Author(s)
Takahashi Y, Sawada T, Akahane T, Kawase Y, Ikeda H, Makino K, Nakamura H, Hide T, Yano S, Hashimoto N, Kamada H.
-
Journal Title
Oncol Lett.
Volume: 14
Issue: 1
Pages: 264-270
DOI
Related Report
Peer Reviewed
-
[Journal Article] Benefit of 3T Diffusion-weighted Imaging in Comparison to Contrast-enhanced MR Imaging for the Evaluation of Disseminated Lesions in Primary Malignant Brain Tumors2017
Author(s)
Kadota Y, Hirai T, Nakamura H, Makino K, Yano S, Nishimura S, Tateishi M, Azuma M, Kitajima M, Yamashita Y
-
Journal Title
Magnetic Resonance in Medical Sciences
Volume: 16
Issue: 3
Pages: 217-222
DOI
NAID
ISSN
1347-3182, 1880-2206
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
