研究者詳細 - 村瀬　和幸

論文 - 村瀬　和幸

分割表示 138 件中 61 - 80 件目／全件表示 >>

Secondary malignant giant cell tumor of bone with histone H3.3 mutation: A case series

Makoto Emori, Satoshi Nagoya, Masato Sugawara, Emi Mizushima, Junya Shimizu, Yasutaka Murahashi, Kazuyuki Murase, Kohichi Takada, Shintaro Sugita, Michiaki Takagi, Tadashi Hasegawa, Toshihiko Yamashita

Journal of Orthopaedic Science ( Elsevier BV ) 2018年12月

DOI

High expression of nucleoporin 133 mRNA in bone marrow CD138+ cells is a poor prognostic factor in multiple myeloma

Soushi Ibata, Masayoshi Kobune, Shohei Kikuchi, Masahiro Yoshida, Shogo Miura, Hiroto Horiguchi, Kazuyuki Murase, Satoshi Iyama, Kohichi Takada, Koji Miyanishi, Junji Kato

Oncotarget ( Impact Journals LLC ) 9 ( 38 ) 25127 - 25135 2018年05月 [査読有り]

Recent advances in plasma cell biology and molecularly-targeted therapy enable us to employ various types of drugs including immunomodulatory drugs, proteasome inhibitors, and immunotherapy. However, the optimal therapeutic strategies to introduce these drugs for heterogeneous patients with multiple myeloma (MM) have not yet been clarified. In the present study, we attempted to identify a new factor indicating poor prognosis in CD138+ myeloma cells using accumulated Gene Expression Omnibus (GEO) datasets from studies of MM and to assess the relationship between gene expression and survival using MAQC-II Project Myeloma (GSE24080). Five GEO datasets (GSE5900, GSE58133, GSE68871, GSE57317 and GSE16791) which were analyzed by the same microarray platform (GLP570) were combined into one MM database including various types of MM. However, we found that gene expression levels were quite heterogeneous. Hence, we focused on the differentially-expressed genes (DEGs) between newlydiagnosed MM and relapsed/refractory MM and found that the expression levels of more than 20 genes changed two-fold or more. Additionally, pathway analysis indicated that six pathways including Hippo signaling were significantly enriched. Then, we applied all DEGs and genes associated with core enrichment for GSE24080 to evaluate their involvement in disease prognosis. We found that nucleoporin 133 (NUP133) is an independent poor prognostic factor by Cox proportional hazard analysis. These results suggested that high expression of NUP133 could be useful when choosing the appropriate MM therapy and may be a new target of MM therapy.

DOI

Clostridium difficile肝膿瘍の1例

松野鉄平, 田中信悟, 宮西浩嗣, 河野豊, 中村元, 坂本拡基, 早坂尚貴, 石川和真, 村瀬和幸, 高田弘一, 高梨訓博, 勝木伸一, 小船雅義, 加藤淳二

肝臓 ( (一社)日本肝臓学会 ) 59 ( 3 ) 180 - 186 2018年03月 [査読有り]

症例は68歳、男性。発熱、心窩部痛を主訴に近医を受診し、肝膿瘍、播種性血管内凝固症候群(DIC)、門脈血栓症と診断され当院へ転院となった。前医にてメロペネムが投与されるも改善傾向を認められなかったが、当院入院時の血液培養検査にてClostridium difficile(C.difficile)が検出され、メトロニダゾール内服を開始したところ速やかに改善した。肝膿瘍および便からもC.difficileが検出され、PCR-rebotypingで全て同一菌株と同定された。血液培養検査でC.difficileが検出されたため早期にメトロニダゾールの投与を開始でき、治癒が得られた肝膿瘍症例を経験した。広域抗菌薬に対する反応が悪い肝膿瘍に対しては、原因菌としてC.difficileも念頭に診断・治療を進めることが必要である。(著者抄録)

A case of cisplatin-refractory advanced pure seminoma showing complete remission after treatment with high-dose carboplatin plus etoposide as fourth-line salvage chemotherapy

Kimihito Tachikawa, Naotaka Nishiyama, Takashi Muranaka, Koichi Takada, Kazuyuki Murase, Tsutomu Kouno, Kato Junji, Naoya Masumori

International Cancer Conference Journal ( Springer Science and Business Media LLC ) 7 ( 1 ) 6 - 10 2018年01月

DOI

ART療法中に多発血栓症を併発した悪性リンパ腫患者の一例

池田博, 吉田正宏, 舘越鮎美, 菊地尚平, 村瀬和幸, 高田弘一, 井山諭, 小船雅義, 村上則子, 宮越郁子, 又村了輔, 國本雄介, 加藤淳二

日本エイズ学会誌 ( (一社)日本エイズ学会 ) 19 ( 4 ) 501 - 501 2017年11月

Small molecule CP-31398 induces reactive oxygen species-dependent apoptosis in human multiple myeloma

Yohei Arihara, Kohichi Takada, Yusuke Kamihara, Naotaka Hayasaka, Hajime Nakamura, Kazuyuki Murase, Hiroshi Ikeda, Satoshi Iyama, Tsutomu Sato, Koji Miyanishi, Masayoshi Kobune, Junji Kato

ONCOTARGET ( IMPACT JOURNALS LLC ) 8 ( 39 ) 65889 - 65899 2017年09月 [査読有り]

Reactive oxygen species (ROS) are normal byproducts of a wide variety of cellular processes. ROS have dual functional roles in cancer cell pathophysiology. At low to moderate levels, ROS act as signaling transducers to activate cell proliferation, migration, invasion, and angiogenesis. In contrast, high levels of ROS induce cell death. In multiple myeloma (MM), ROS overproduction is the trigger for apoptosis induced by several anticancer compounds, including proteasome inhibitors. However, no drugs for which oxidative stress is the main mechanism of action are currently used for treatment of MM in clinical situations. In this study, we demonstrate that the p53-activating small molecule CP-31398 (CP) effectively inhibits the growth of MM cell lines and primary MM isolates from patients. CP also suppresses the growth of MM xenografts in mice. Mechanistically, CP was found to induce intrinsic apoptosis in MM cells via increasing ROS production. Interestingly, CP-induced apoptosis occurs regardless of the p53 status, suggesting that CP has additional mechanisms of action. Our findings thus indicate that CP could be an attractive candidate for treatment of MM patients harboring p53 abnormalities; this satisfies an unmet clinical need, as such individuals currently have a poor prognosis.

DOI PubMed

[A Case of Chronic Myelogenous Leukemia That Developed Fibrous Pericarditis Owing to Nilotinib Use].

Miura S, Murase K, Sakurada A, Takada K, Iyama S, Sato T, Sato Y, Miyanishi K, Kobune M, Muranaka A, Tachibana K, Kato J

Gan to kagaku ryoho. Cancer & chemotherapy 44 ( 6 ) 529 - 531 2017年06月 [査読有り] [国内誌]

A 64-year-old man was diagnosed with chronic-phase chronic myelogenous leukemia(CML)in May 2009. He was treated with imatinib and achieved complete cytogenetic response(CCyR)in 2 months. After 4 months of treatment, he developed interstitial pneumonia and became intolerant to imatinib. He was then switched to nilotinib from October of the same year. In June 2013, he was diagnosed with drug-induced pericarditis resulting from nilotinib use, and thus, nilotinib was discontinued. Subsequently, he was followed up without specific treatment for CML. In January 2014, he was admitted to the Dept. of Cardiovascular, Renal and Metabolic Medicine at our hospital because of heart failure. After examinations of cardiac function, he was diagnosed with constrictive pericarditis. Therefore, pericardiolysis was performed by the Dept. of Cardiovascular Surgery at our hospital. Pathologic findings showed hyaline-like fibrous tissue proliferation in the pericardium, which was diagnosed as fibrous pericarditis induced by nilotinib. We report a case of chronic myelogenous leukemia that developed fibrous pericarditis owing to nilotinib use.

PubMed

肝細胞癌の治療前ステージングにおけるEOB-MRIおよびDiffusion-Weighted Imagingの有用性についての検討

坂本拡基, 宮西浩嗣, 田中信吾, 河野豊, 中村元, 櫻田晃, 石川和真, 佐藤昌則, 菊地尚平, 村瀬和幸, 高田弘一, 加藤淳二

肝臓 ( (一社)日本肝臓学会 ) 58 ( Suppl.1 ) A296 - A296 2017年04月 [査読有り]

A typical presentation of primary pulmonary epithelioid sarcoma misdiagnosed as non-small cell lung cancer

Makoto Emori, Mitsuharu Tamakawa, Mitsunori Kaya, Kohichi Takada, Kazuyuki Murase, Chisa Fujita, Sayuri Sato, Ryuji Takahashi, Kanako C. Hatanaka, Shintaro Sugita, Hiroshi Hirano, Toshihiko Yamashita, Tadashi Hasegawa

Pathology International ( Wiley ) 67 ( 4 ) 222 - 224 2017年04月

DOI

低分子化合物CP-31398は多発性骨髄腫に対して活性酸素種依存的なアポトーシスを誘導する

在原洋平, 高田弘一, 神原悠輔, 河野豊, 早坂尚貴, 中村元, 菊地尚平, 村瀬和幸, 井山諭, 池田博, 佐藤勉, 宮西浩嗣, 小船雅義, 加藤淳二

International Journal of Myeloma ( 日本骨髄腫学会 ) 7 ( 1 ) 76 - 76 2017年04月 [査読有り]

非アルコール性脂肪性肝疾患の組織学的診断時における肝発癌予測因子についての検討

田中信悟, 宮西浩嗣, 坂本拡基, 佐藤昌則, 櫻田晃, 池田裕貴, 石川和真, 河野豊, 村瀬和幸, 高田弘一, 加藤淳二

日本消化器病学会雑誌 ( (一財)日本消化器病学会 ) 114 ( 臨増総会 ) A311 - A311 2017年03月 [査読有り]

Activated p53 with Histone Deacetylase Inhibitor Enhances L-Fucose-Mediated Drug Delivery through Induction of Fucosyltransferase 8 Expression in Hepatocellular Carcinoma Cells

Yutaka Okagawa, Kohichi Takada, Yohei Arihara, Shohei Kikuchi, Takahiro Osuga, Hajime Nakamura, Yusuke Kamihara, Naotaka Hayasaka, Makoto Usami, Kazuyuki Murase, Koji Miyanishi, Masayoshi Kobune, Junji Kato

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 11 ( 12 ) 2016年12月 [査読有り]

Background The prognosis of advanced hepatocellular carcinoma (HCC) is dismal, underscoring the need for novel effective treatments. The alpha 1,6-fucosyltransferase (fucosyltransferase 8, FUT8) has been reported to accelerate malignant potential in HCC. Our study aimed to investigate the regulation of FUT8 expression by p53 and develop a novel therapeutic strategy for targeting HCC cells using L-fucose-mediated drug delivery. Methods Binding sites for p53 were searched for within the FUT8 promoter region. FUT8 expression was assessed by immunoblotting. Chromatin immunoprecipitation (ChIP) assays were performed to analyze p53 binding to the FUT8 promoter. The delivery of Cy5.5-encapsulated L-fucose-liposomes (Fuc-Lip-Cy5.5) to a Lens Culinaris agglutinin-reactive fraction of a-fetoprotein (AFP-L3)-expressing HCC cells was analyzed by flow cytometry. The induction of FUT8 by histone deacetylase inhibitor (HDACi) -inducing acetylated -p53 was evaluated by immunoblotting. Flow cytometric analysis was performed to assess whether the activation of p53 by HDACi affected the uptake of Fuc-Lip-Cy5.5 by HCC cells. The cytotoxicity of an L-fucose-bound liposome carrying sorafenib (Fuc-Lip-sorafenib) with HDACi was assessed in vivo and in vitro. Results The knock down of p53 with siRNA led to decreased FUT8 expression. ChIP assays revealed p53 binds to the FUT8 promoter region. Flow cytometric analyses demonstrated the specific uptake of Fuc-Lip-Cy5.5 into AFP-L3-expressing HCC cells in a p53- and FUT8- dependent manner. HDACi upregulated the uptake of Fuc-Lip-Cy5.5 by HCC cells by increasing FUT8 via acetylated -p53. The addition of a HDACi increased apoptosis induced by Fuc-Lip-sorafenib in HCC cells. Conclusions Our findings reveal that FUT8 is a p53 target gene and suggest that p53 activated by HDACi induces Fuc-Lip-sorafenib uptake by HCC cells, highlighting this pathway as a promising therapeutic intervention for HCC.

DOI

A phase II trial of small-dose bortezomib, lenalidomide and dexamethasone (sVRD) as consolidation/maintenance therapy in patients with multiple myeloma

Soushi Ibata, Tsutomu Sato, Hiroyuki Kuroda, Yasuhiro Nagamachi, Satoshi Iyama, Akihito Fujimi, Yusuke Kamihara, Yuichi Konuma, Masahiro Yoshida, Ayumi Tatekoshi, Akari Hashimoto, Hiroto Horiguchi, Kaoru Ono, Kazuyuki Murase, Kohichi Takada, Koji Miyanishi, Masayoshi Kobune, Yasuo Hirayama, Junji Kato

CANCER CHEMOTHERAPY AND PHARMACOLOGY ( SPRINGER ) 78 ( 5 ) 1041 - 1049 2016年11月 [査読有り]

Consolidation/maintenance therapy induces deep remission in patients with multiple myeloma (MM); however, the most suitable regimen has been under investigation. The combination therapy with bortezomib, lenalidomide and dexamethasone (VRD) is a powerful regimen for relapsed/refractory as well as newly diagnosed MM as an induction therapy. However, severe adverse events (AEs) may become a problem when VRD is introduced without dose reduction as a consolidation/maintenance therapy. In this single-arm phase II study, we evaluated the efficacy of small-dose VRD regimen (sVRD) in the consolidation/maintenance setting. Sixteen patients who had partial response (PR) or better after any induction therapy were enrolled. Patients received at least six 28-day cycles of subcutaneous bortezomib (1.3 mg/m(2) on days 1 and 15), lenalidomide (10 mg on days 1-21) and dexamethasone (40 mg on days 1, 8, 15 and 22). The overall response rate and the complete response (CR) rate were 100 and 43.8 %, respectively. In particular, one patient with CR and two patients with very good PR at enrollment achieved stringent CR during 6 courses of sVRD. With a median follow-up time of 29.4 months, the median progression-free survival (PFS) and overall survival (OS) were not reached, while the PFS and OS rates at 2.5 years were 66.6 and 77.3 %, respectively. Univariate analysis demonstrated that disease progression as a reason for discontinuation of sVRD had a negative impact on OS. There were no grade 3 or 4 hematologic or nonhematologic AEs. Our sVRD regimen as a consolidation/maintenance therapy was highly effective and well tolerable.

DOI PubMed

The iron chelator deferasirox induces apoptosis by targeting oncogenic Pyk2/β-catenin signaling in human multiple myeloma.

Kamihara Y, Takada K, Sato T, Kawano Y, Murase K, Arihara Y, Kikuchi S, Hayasaka N, Usami M, Iyama S, Miyanishi K, Sato Y, Kobune M, Kato J

Oncotarget 7 ( 39 ) 64330 - 64341 2016年09月 [査読有り] [国際誌]

Deregulated iron metabolism underlies the pathogenesis of many human cancers. Recently, low expression of ferroportin, which is the only identified non-heme iron exporter, has been associated with significantly reduced overall survival in multiple myeloma (MM); however, the altered iron metabolism in MM biology remains unclear. In this study we demonstrated, by live cell imaging, that MM cells have increased intracellular iron levels as compared with normal cells. In experiments to test the effect of iron chelation on the growth of MM cells, we found that deferasirox (DFX), an oral iron chelator used to treat iron overload in clinical practice, inhibits MM cell growth both in vivo and in vitro. Mechanistically, DFX was found to induce apoptosis of MM cells via the inhibition of proline-rich tyrosine kinase 2 (Pyk2), which is known to promote tumor growth in MM. Inhibition of Pyk2 is caused by the suppression of reactive oxygen species, and leads to downregulation of the Wnt/β-catenin signaling pathway. Taken together, our findings indicate that high levels of intracellular iron, which might be due to low ferroportin expression, play a role in MM pathophysiology. Therefore, DFX may provide a therapeutic option for MM that is driven by deregulated iron homeostasis and/or Pyk2/Wnt signaling.

DOI PubMed

[Treatment Outcomes of Adult-Onset Ewing Sarcoma: A Single-Center Retrospective Study of Five Cases].

Murase K, Takada K, Kamihara Y, Usami M, Yoshida M, Tatekoshi A, Hashimoto A, Arihara Y, Hayasaka N, Miura S, Iyama S, Sato T, Sato Y, Miyanishi K, Kobune M, Emori M, Kaya M, Yamashita T, Sugita S, Hasegawa T, Kato J

Gan to kagaku ryoho. Cancer & chemotherapy 43 ( 8 ) 1015 - 8 2016年08月 [査読有り] [国内誌]

UNLABELLED: We report the treatment outcomes of 5 cases of adult-onset Ewing sarcoma(ES)managed between 2011 and 2014. We examined prognostic factors including the primary lesion, tumor size, metastatic status, and serum LDH levels. RESULTS: The locations of the primary lesions included the limbs in 1 case and the trunk in 4; the cases in the trunk had a worse prognosis than that in the limbs. Tumor size was greater than 8 cm in only 1 patient, who also displayed evidence of metastases at presentation and high LDH levels. All the patients received chemotherapy consisting of alternating vincristine, doxorubicin, and cyclophosphamide(VDC)and etoposide and ifosfamide(IE). Surgery was selected for the treatment of 4 patients, and radiotherapy was administered to 1 patient for local treatment of the tumor. A median follow-up duration of 31.6 months revealed the 2-year overall survival rate and progression-free survival rate to be 80.0%. CONCLUSIONS: The prognosis of patients with adult-onset ES is poor; however, combined modality therapy, including VDC-IE, was demonstrated to improve the outcome of patients in the present study. Nevertheless, the patient with tumor size exceeding 8 cm, metastasis, and high LDH levels, relapsed 1 year after treatment, as reported previously. Further investigation is required to clarify the factors affecting prognosis in adults, and to develop effective therapies for patients with a poor prognosis.

PubMed

肛門周囲の感覚障害で発症し、前立腺生検にて診断に至った血管内リンパ腫(IVL)の1例

齋藤太郎, 中村祐貴, 鈴木秀一郎, 津田笑子, 林貴士, 齊藤正樹, 久原真, 川又純, 下濱俊, 村瀬和幸, 高田弘一

臨床神経学 ( (一社)日本神経学会 ) 56 ( 6 ) 451 - 451 2016年06月

Isoform D of vascular endothelial growth factor in systemic capillary leak syndrome: a case report.

Ibata S, Sato T, Takada K, Tatekoshi A, Hashimoto A, Kamihara Y, Jomen W, Horiguchi H, Ono K, Murase K, Iyama S, Miyanishi K, Sato Y, Takimoto R, Kobune M, Kato J

Journal of medical case reports 10 125 - 125 2016年05月 [査読有り] [国際誌]

BACKGROUND: Systemic capillary leak syndrome is a rare condition characterized by episodic attacks of hypovolemia due to systemic capillary hyperpermeability, which results in profound hypotension and edema. Although the implication of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 has been suggested, the pathogenesis of systemic capillary leak syndrome remains unclear. In this report, we describe a case of systemic capillary leak syndrome in which serum isoform D of vascular endothelial growth factor was elevated. To the best of our knowledge, this is the first reported case of systemic capillary leak syndrome in which isoform D of vascular endothelial growth factor is suggested as the plausible biomarker. CASE PRESENTATION: A 41-year-old Japanese man was transferred to our emergency department. He was hypotensive, tachycardic, and edematous over the trunk and all four limbs. He received aggressive intravenous fluid therapy and underwent fasciotomy of the right forearm to prevent muscle necrosis. A diagnosis of systemic capillary leak syndrome was suspected. The presence of serum monoclonal immunoglobulin G and κ light chain supported this diagnosis. Prevention of hypotensive crises was unsuccessfully attempted with theophylline, intravenous immunoglobulin, high-dose dexamethasone, bortezomib, melphalan, and prednisolone; however, the patient's attacks dramatically disappeared after the introduction of thalidomide. The serum of the patient was stored soon after the onset of hypotensive crisis and analyzed to profile possible mediators responsible for the capillary leak. The concentration of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 were all within normal ranges. Meanwhile, we found that isoform D of vascular endothelial growth factor was elevated, which was normalized after the introduction of thalidomide. CONCLUSIONS: In our patient, isoform D of vascular endothelial growth factor (instead of vascular endothelial growth factor) may have been a causative factor of hypotensive crises, since isoform D contributes to vascular endothelial growth factor receptor-2 signaling, which is the major mediator of the permeability-enhancing effects of vascular endothelial growth factor. We suggest the measurement of isoform D of vascular endothelial growth factor in patients with systemic capillary leak syndrome in whose serum vascular endothelial growth factor is not elevated.

DOI PubMed

Extracellular vesicle miR-7977 is involved in hematopoietic dysfunction of mesenchymal stromal cells via poly(rC) binding protein 1 reduction in myeloid neoplasms

Hiroto Horiguchi, Masayoshi Kobune, Shohei Kikuchi, Masahiro Yoshida, Masaki Murata, Kazuyuki Murase, Satoshi Iyama, Kohichi Takada, Tsutomu Sato, Kaoru Ono, Akari Hashimoto, Ayumi Tatekoshi, Yusuke Kamihara, Yutaka Kawano, Koji Miyanishi, Norimasa Sawada, Junji Kato

HAEMATOLOGICA ( FERRATA STORTI FOUNDATION ) 101 ( 4 ) 437 - 447 2016年04月 [査読有り]

The failure of normal hematopoiesis is observed in myeloid neoplasms. However, the precise mechanisms governing the replacement of normal hematopoietic stem cells in their niche by myeloid neoplasm stem cells have not yet been clarified. Primary acute myeloid leukemia and myelodysplastic syndrome cells induced aberrant expression of multiple hematopoietic factors including Jagged-1, stem cell factor and angiopoietin-1 in mesenchymal stem cells even in non-contact conditions, and this abnormality was reverted by extracellular vesicle inhibition. Importantly, the transfer of myeloid neoplasm-derived extracellular vesicles reduced the hematopoietic supportive capacity of mesenchymal stem cells. Analysis of extracellular vesicle microRNA indicated that several species, including miR-7977 from acute myeloid leukemia cells, were higher than those from normal CD34(+) cells. Remarkably, the copy number of miR-7977 in bone marrow interstitial fluid was elevated not only in acute myeloid leukemia, but also in myelodysplastic syndrome, as compared with lymphoma without bone marrow localization. The transfection of the miR-7977 mimic reduced the expression of the posttranscriptional regulator, poly(rC) binding protein 1, in mesenchymal stem cells. Moreover, the miR-7977 mimic induced aberrant reduction of hematopoietic growth factors in mesenchymal stem cells, resulting in decreased hematopoietic-supporting capacity of bone marrow CD34(+) cells. Furthermore, the reduction of hematopoietic growth factors including Jagged-1, stem cell factor and angiopoietin-1 were reverted by target protection of poly(rC) binding protein 1, suggesting that poly(rC) binding protein 1 could be involved in the stabilization of several growth factors. Thus, miR-7977 in extracellular vesicles may be a critical factor that induces failure of normal hematopoiesis via poly(rC) binding protein 1 suppression.

DOI PubMed

Narrow-Band Ultraviolet B Phototherapy Ameliorates Acute Graft-Versus-Host Disease of the Intestine by Expansion of Regulatory T Cells.

Hashimoto A, Sato T, Iyama S, Yoshida M, Ibata S, Tatekoshi A, Kamihara Y, Horiguchi H, Murase K, Kawano Y, Takada K, Miyanishi K, Kobune M, Ichimiya S, Kato J

PloS one 11 ( 3 ) e0152823 2016年03月 [査読有り]

DOI PubMed

RNAi-mediated gene silencing of ST6GalNAc I suppresses the metastatic potential in gastric cancer cells

Fumito Tamura, Yasushi Sato, Masahiro Hirakawa, Makoto Yoshida, Michihiro Ono, Takahiro Osuga, Yutaka Okagawa, Naoki Uemura, Yohei Arihara, Kazuyuki Murase, Yutaka Kawano, Satoshi Iyama, Kohichi Takada, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto, Junji Kato

GASTRIC CANCER ( SPRINGER ) 19 ( 1 ) 85 - 97 2016年01月 [査読有り]

ST6GalNAc I is a sialyltransferase controlling the expression of sialyl-Tn antigen (STn), which is overexpressed in several epithelial cancers, including gastric cancer, and is highly correlated with cancer metastasis. However, the functional contribution of ST6GalNAc I to development or progression of gastric cancer remains unclear. In this study, we investigated the effects of suppression of ST6GalNAc I on gastric cancer in vitro and in vivo. Gastric cancer cell lines were transfected with ST6GalNAc I siRNA and were examined by cell proliferation, migration, and invasion assays. We also evaluated the effect of ST6GalNAc I siRNA treatment in a peritoneal dissemination mouse model. The differences in mRNA levels of selected signaling molecules were analyzed by polymerase chain reaction (PCR) arrays associated with tumor metastasis in MKN45 cells. The signal transducer and activator of transcription 5b (STAT5b) signaling pathways that reportedly regulate the insulin-like growth factor-1 (IGF-1) were analyzed by Western blot. ST6GalNAc I siRNA inhibited gastric cancer cell growth, migration, and invasion in vitro. Furthermore, intraperitoneal administration of ST6GalNAc I siRNA- liposome significantly inhibited peritoneal dissemination and prolonged the survival of xenograft model mice with peritoneal dissemination of gastric cancer. PCR array confirmed that suppression of ST6GalNAc I caused a significant reduction in expression of IGF-1 mRNA. Decreased IGF-1 expression in MKN45 cells treated with ST6GalNAc I siRNA was accompanied by reduced phosphorylation of STAT5b. ST6GalNAc I may regulate the gene expression of IGF-1 through STAT5b activation in gastric cancer cells and may be a potential target for treatment of metastasizing gastric cancer.

DOI PubMed

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