医学部 病理学
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Scientific reports, 14(1) 18494-18494, Aug 9, 2024Adipocyte-cancer cell interactions promote tumor development and progression. Previously, we identified adipsin (CFD) and its downstream effector, hepatocyte growth factor (HGF), as adipokines that enhance adipocyte-breast cancer stem cell interactions. Here, we show that adipsin-dependent adipocyte maturation and the subsequent upregulation of HGF promote tumor invasion in breast cancers. Mature adipocytes, but not their precursors, significantly induced breast tumor cell migration and invasion in an adipsin expression-dependent manner. Promoters of tumor invasion, galectin 7 and matrix metalloproteinases, were significantly upregulated in cancer cells cocultured with mature adipocytes; meanwhile, their expression levels in cancer cells cocultured with adipocytes were reduced by adipsin knockout (Cfd KO) or a competitive inhibitor of CFD. Tumor growth and distant metastasis of mammary cancer cells were significantly suppressed when syngeneic mammary cancer cells were transplanted into Cfd KO mice. Histological analyses revealed reductions in capsular formation and tumor invasion at the cancer-adipocyte interface in the mammary tumors formed in Cfd KO mice. These findings indicate that adipsin-dependent adipocyte maturation may play an important role in adipocyte-cancer cell interaction and breast cancer progression.
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Genes to Cells, 28(5) 364-373, Mar 12, 2023<jats:title>Abstract</jats:title><jats:p>Epithelial–mesenchymal transition (EMT) plays a pivotal role in cancer metastasis and treatment resistance, which worsens prognosis. In phase III trials, eribulin improved overall survival in metastatic breast cancer (MBC) patients. In preclinical studies, eribulin suppressed EMT. However, clinical data on the use of eribulin for MBC patients are limited. In this exploratory, prospective study, we examined the effect of eribulin on EMT in MBC patients. Twenty‐two patients aged 44–82 years with recurrent breast cancer or MBC were treated with eribulin. Breast cancer tissue samples were obtained before treatment and on Day 15 ± 5 of the first cycle of eribulin treatment. EMT markers (E‐cadherin, claudin‐3, vimentin, and N‐cadherin) were analyzed using western blotting. EMT changes were evaluated based on the ratio of epithelial to mesenchymal markers before and after treatment in individual tumors. E‐cadherin/vimentin, claudin‐3/vimentin, E‐cadherin/N‐cadherin, and claudin‐3/N‐cadherin ratios were significantly higher after treatment (<jats:italic>p</jats:italic> = .007, <jats:italic>p</jats:italic> = .005, <jats:italic>p</jats:italic> = .006, and <jats:italic>p</jats:italic> = .011, respectively). Based on E‐cadherin/vimentin, 65.0% of tumors shifted to an epithelial phenotype, as compared to 66.7% based on claudin‐3/vimentin, 84.6% based on E‐cadherin/N‐cadherin, and 71.4% based on claudin‐3/N‐cadherin ratios. Thus, our results showed that eribulin suppressed EMT in breast cancer tissues.</jats:p>
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Current Biology, 32(7) 1485-1496.e4, Apr, 2022
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Scientific Reports, 11(1) 10729, May 24, 2021<jats:title>Abstract</jats:title><jats:p>For pituitary regenerative medicine, the creation of a hypophyseal model in monkeys is necessary to conduct future preclinical studies; however, previous studies reported that hypophysectomy in monkeys is not always safe or satisfactory. This study aimed to create a hypophyseal dysfunction model in a cynomolgus monkey using a safer surgical technique and establish the protocol of pituitary hormone replacement therapy for this model. Surgical resection of the pituitary gland of a 7.8-year-old healthy adult cynomolgus male monkey weighing 5.45 kg was performed to create a hypophyseal dysfunction model for future regenerative studies. Endoscopic transoral transsphenoidal surgery was used to perform hypophysectomy under navigation support. These procedures were useful for confirming total removal of the pituitary gland without additional bone removal and preventing complications such as cerebrospinal fluid leakage. Total removal was confirmed by pathological examination and computed tomography. Hypopituitarism was verified with endocrinological examinations including stimulation tests. Postoperatively, the monkey’s general condition of hypopituitarism was treated with hormone replacement therapy, resulting in long-term survival. The success of a minimally invasive and safe surgical method and long-term survival indicate the creation of a hypophyseal dysfunction model in a cynomolgus monkey; hence, this protocol can be employed in the future.</jats:p>
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Biochemical and Biophysical Research Communications, 532(3) 406-413, Nov, 2020
Misc.
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日本癌学会総会記事, 82回 978-978, Sep, 2023
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日本癌学会総会記事, 82回 1349-1349, Sep, 2023
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日本癌学会総会記事, 82回 978-978, Sep, 2023
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日本癌学会総会記事, 82回 1349-1349, Sep, 2023
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日本癌学会総会記事, 81回 P-2287, Sep, 2022