翔科生物蛋白芯片技術(shù)在醫(yī)學(xué)研究的應(yīng)用重慶腫瘤-文庫吧
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【正文】 Blinded test set 42 AD, 39 NDC, 11 OD Alz vs. 其他老年癡呆癥 準(zhǔn)確度 89% Blinded test set 47 MCI 預(yù)測 Alz 準(zhǔn)確度 81% 人細(xì)胞因子抗體芯片 1000 (AAHCYT1000) 2022年 7月最新 Nature 腫瘤微環(huán)境通過 分泌 HGF引起對 RAF抑制劑的先天抵抗 癌細(xì)胞不死之謎 Nature. 2022 Jul 26。487(7408):5004. 實驗思路 ? 1 提出假設(shè) 腫瘤微環(huán)境與腫瘤的抗藥性有關(guān) ? 2 設(shè)計實驗 篩選上清因子（ AAHCYTG4000(274個因子 ) （ AAHBLG1 (507個因子 ) 腫瘤細(xì)胞 (45)和 stromal cell line or primary cells共培養(yǎng) (23) HGF responsible for rescue. 鑒定 HGF的作用 Nature. 2022 Jul 26。487(7408):5004. PLX4720 AAHCYTG4000(274個因子 ) AAHBLG1 (507個因子 ) Nature. 2022 Jul 26。487(7408):5004. Stromal cell line Rescue score LL 86 * Wi38 * PC60163A1* Hs888Lu * CCD13Lu * PC87985B1 * CCD8Lu HS5 CCD1068Sk HDF HUVECCS PC87399A1 PC87322A1 CCD1090Sk CCD1117Sk CCD1065Sk HMF CCD1069Sk Correlations between proteins secreted by stromal cells and stromal average melanoma rescue scores 鑒定 HGF的作用 其他 RTK配體是否也會與抗藥性相關(guān) In vitro 鑒定 WB 鑒定 HGF/MET通路機制 In vivo 鑒定 BRAFi PLX4720 腫瘤微環(huán)境通過 分泌 HGF引起先天抵抗 RAF抑制劑 （ AAHCYTG4000(274個因子 ) （ AAHBLG1 (507個因子 ) Without our technology, such breakthrough discovery will not be possible. 2022年 8月 : 皮質(zhì)類固醇抑制嬰幼兒血管瘤源性干細(xì)胞內(nèi)的 VEGFA分泌 uPAR, IL6, MCP1, and MMP1 are downregulated in HemSC3 treated with dexamethasone 人血管生成抗體玻璃芯片 1: AAHANGG1000； （檢測 43種不同的細(xì)胞因子） uPAR, IL6, MCP1, and MMP1 are downregulated in HemSC3 treated with dexamethasone 人血管生成抗體玻璃芯片 1: AAHANGG1000； Identification of key factors in tumorigenesis ? YAP (yesassociated protein) – A transcriptional regulator with key roles in both malignancy and in normal an proliferation – Promotes epithelialtomesenchymal transition – Highly upregulated in cancers Preliminary Data MCF10A: a mammary epithelial cell line (nontransformed) (3D culture growth) MCF10A cells YAP transfection OR rebinant EGF ProliferationSurvival YAPexpressing cells also induce proliferation in nonYAPexpressing cells in coculture. What are the key transcriptional targets involved in YAPmediated cell proliferation? Empty vector YAPS127A Amphiregulin (AR) (+) EGF () EGF RayBio174。 Human Growth Factor Array I (AAHGF1) IGFBP6 MCSFR PDGFAA Supernates from transfected MCF10A 3D culture system Amphiregulin is the key transcriptional target of YAP Since Amphiregulin is a ligand for the ErbB receptors, RayBio174。 EGFR Phosphorylation Antibody Arrays were utilized. Empty Vector (+) EGF () EGF YAP activation increases the phosphorylation of classic EGFR target residues RayBio174。 EGFR Phosphorylation Array (AAHPER1) Transfected MCF10A 3D cultureed cell lysates YAPS127A EGFR Tyr845 ErbB4 Tyr1284 EGFR Tyr1148 Conclusion Zhang J, et al. YAPdependent induction of amphiregulin identifies a noncellautonomous ponent of the Hippo pathway. Nat Cell Biol 2022。 11(12): 14441451. Amphiregulin EGFR family YAP Cell proliferation 1. Reversible tyrosine phosphorylation is governed by the balanced action of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). 2. Dysregulation of PTP activity results in aberrant tyrosine phosphorylation, which is frequently implicated in the progression of various diseases including diabetes, rheumatoid arthritis, and cancer . 3. The first PRL associated with cancer metastasis was PRL3 (PTP4A3), which was found to be consistently expressed at high levels in all 18 human colorectal cancer (CRC) liver metastases examined, but at lower levels in the corresponding primary tumors and normal epithelium. Hypothesis: PRL3 plays a key role in cancer metastasis? Alaidaroos et al. J Clin Invest. 202
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