東京大学 · 医学
Dai Shida教授の研究室では、サブセルラー内での脂質メタボライト、特にスフィンゴシルリピッドとリン酸リソスファチジルエタノールアミド(LPA)のシグナル伝達ががん進展に与える影響を、細胞生物学的・分子生物学的アプローチを用いて解明しています。特にS1PやLPAが腫瘍微小環境において細胞増殖・移動を促進するメカニズムや、SphK1の発現制御、およびRTK(EGFRやc-Met)とのクロストークン化の分子機構に注目しています。また、臨床的応用としてもERASプロトコルの効果に関する研究を通じて、がん治療における患者中心のケアの実現を目指しています。
Figures are computed from collected data and may differ slightly.
Sphingolipid metabolites have emerged as critical players in a number of fundamental biological processes. Among them, sphingosine-1-phosphate (S1P) promotes cell survival and proliferation, in contrast to ceramide and sphingosine, which induce cell growth arrest and apoptosis. These sphingolipids with opposing functions are interconvertible inside cells, suggesting that a finely tuned balance between them can determine cell fate. Sphingosine kinases (SphKs), which catalyze the phosphorylation o
Lysophosphatidic acid (LPA) is a lipid mediator with diverse effects on various cells. Here, we investigated the effects of LPA on human colon carcinoma DLD1 cells. Northern blot analysis revealed that DLD1 highly expressed LPA1/Edg-2 but showed only low expression of LPA2/Edg-4 and no expression of LPA3/Edg-7 at the mRNA level. Western blot analysis revealed that DLD1 cells highly expressed LPA1 at the protein level. Using the Boyden chamber assay, LPA markedly increased DLD1 cell migration at
Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are lysophospholipid mediators of diverse cellular processes important for cancer progression. S1P is produced by two sphingosine kinases, SphK1 and SphK2. Expression of SphK1 is elevated in many cancers. Here, we report that LPA markedly enhanced SphK1 mRNA and protein in gastric cancer MKN1 cells but had no effect on SphK2. LPA also up-regulated SphK1 expression in other human cancer cells that endogenously express the LPA(1) recept
Modified ERAS protocols for obstructive colorectal cancer reduced hospital stay without adversely affecting morbidity, indicating that ERAS protocols are feasible for patients with obstructive colorectal cancer.
This study clearly demonstrated that the quality of recovery based on patient-reported outcomes is in agreement with discharge around POD6 for colorectal cancer patients under ERAS.
Receptor tyrosine kinases (RTKs) are transactivated by the stimulation of G protein-coupled receptors (GPCRs). Sphingosine 1-phosphate (S1P), a ligand of GPCR, is known as a tumor-promoting lipid, but its signaling pathways are not fully understood. We here demonstrated that S1P induces rapid and transient tyrosine phosphorylation of epidermal growth factor receptor (EGFR) and c-Met in gastric cancer cells, both of which have been proposed as prognostic markers of gastric cancers. The pathway of
CONUT score, PNI, and mGPS were found to be independent prognostic factors for OS in patients with stage IV CRC, suggesting that nutritional and inflammatory status is a useful host-related prognostic indicator in stage IV CRC.
Staging classification is updated regularly, which clinicians should always catch up with.
Leptin is known to act as a growth factor through the Janus-activated kinase (JAK)/signal transducer and activator of transcription signaling pathway as well as the mitogen-activated protein kinase pathway. In this study, we showed a novel signal transduction pathway using two human gastric cancer cell lines, MKN28 and MKN74. Both gastric cancer cells expressed leptin and its receptors (Ob-R) at the protein level. We found that leptin, even at as low as 0.1 ng/mL, induced significant tyrosine ph
ERAS protocols for colorectal surgery helped reduce the length of postoperative hospital stay without adversely affecting morbidity, indicating that ERAS protocols are feasible and effective in Japanese settings as well.
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