The study consists of a Phase1b lead-in portion to determine the maximum tolerated dose (MTD) of OMP-59R5 in combination with nab-paclitaxel and gemcitabine followed by a Phase 2, multicenter, randomized, placebo-controlled portion to evaluate the efficacy and safety of OMP-59R5 in combination with nab-paclitaxel and gemcitabine in subjects with previously untreated stage IV pancreatic cancer.

开始日期2012-10-01

申办/合作机构

Mereo BioPharma 5, Inc.

100 项与 Notch-2 x Notch-3 相关的临床结果

登录后查看更多信息

100 项与 Notch-2 x Notch-3 相关的转化医学

登录后查看更多信息

0 项与 Notch-2 x Notch-3 相关的专利（医药）

登录后查看更多信息

280

项与 Notch-2 x Notch-3 相关的文献（医药）

2024-11-01·Journal of Investigative Dermatology

ASH2L Mediates Epidermal Differentiation and Hair Follicle Morphogenesis through H3K4me3 Modification

Article

作者: Wang, Qirui ; Zhou, Renpeng ; Wang, Danru ; Liang, Yimin ; Zeng, Siyi

The processes of epidermal development in mammals are regulated by complex molecular mechanisms, such as histone modifications. Histone H3 lysine K4 methylation mediated by COMPASS (complex of proteins associated with Set1) methyltransferase is associated with gene activation, but its effect on epidermal lineage development remains unclear. Therefore, we constructed a mouse model of specific ASH2L (COMPASS methyltransferase core subunit) deletion in epidermal progenitor cells and investigated its effect on the development of mouse epidermal lineage. Furthermore, downstream target genes regulated by H3K4me3 were screened using RNA sequencing combined with Cleavage Under Targets and Tagmentation sequencing. Deletion of ASH2L in epidermal progenitor cells caused thinning of the suprabasal layer of the epidermis and delayed hair follicle morphogenesis in newborn mice. These phenotypes may be related to the reduced proliferative capacity of epidermal and hair follicle progenitor cells. ASH2L depletion may also lead to depletion of the epidermal stem cell pools in late mouse development. Finally, genes related to hair follicle development (Shh, Edar, and Fzd6), Notch signaling pathway (Notch2, Notch3, Hes5, and Nrarp), and ΔNp63 were identified as downstream target genes regulated by H3K4me3. Collectively, ASH2L-dependent H3K4me3 modification served as an upstream epigenetic regulator in epidermal differentiation and hair follicle morphogenesis in mice.

2024-10-01·Life Science Alliance

C/EBPβ deletion in macrophages impairs mammary gland alveolar budding during the estrous cycle

Article

作者: Bandyopadhyay, Ishitri ; Phillips, Emily S ; Burke, Caitlin M ; Embrey, Samuel J ; Qiu, Yinjie ; Machado, Heather L ; Rojo, Michelle D ; Sturtz, Alexa D ; LaRue, Rebecca ; Matherne, Megan G ; Schwertfeger, Kathryn L

Macrophages have important roles in mammary gland development and tissue homeostasis, but the specific mechanisms that regulate macrophage function need further elucidation. We have identified C/EBPβ as an important transcription factor expressed by multiple macrophage populations in the normal mammary gland. Mammary glands from mice with C/EBPβ-deficient macrophages ( CebpbΔM ) show a significant decrease in alveolar budding during the diestrus stage of the reproductive cycle, whereas branching morphogenesis remains unchanged. Defects in alveolar budding were found to be the result of both systemic hormones and local macrophage-directed signals. RNA sequencing shows significant changes in PR-responsive genes and alterations in the Wnt landscape of mammary epithelial cells of CebpbΔM mice, which regulate stem cell expansion during diestrus. CebpbΔM macrophages demonstrate a shift from a pro-inflammatory to a tissue-reparative phenotype, and exhibit increased phagocytic capacity as compared to WT. Finally, CebpbΔM macrophages down-regulate Notch2 and Notch3 , which normally promote stem cell expansion during alveolar budding. These results suggest that C/EBPβ is an important macrophage factor that facilitates macrophage–epithelial crosstalk during a key stage of mammary gland tissue homeostasis.

2024-06-01·Zhongguo shi yan xue ye xue za zhi

[The Role of Notch Signaling Pathway in Adult Patients with Epstein-Barr Virus-induced Infectious Mononucleosis].

Article

作者: Li, Lian-Xiang ; Gao, Ying ; Li, Yu

题目Notch信号通路在成人EB病毒感染所致传染性单核细胞增多症中的作用.目的观察成人传染性单核细胞增多症（IM）患者Notch信号通路分子和Th22细胞的变化，检测抑制Notch信号通路对Th22细胞的调控作用。.方法纳入42例IM患者和21例健康对照者，采集外周血，分离血浆和外周血单个核细胞，酶联免疫吸附试验检测血浆白细胞介素（IL）-17和IL-22水平，流式细胞术检测CD3⁺ CD4⁺ IL-17⁺ Th17细胞和CD3⁺ CD4⁺ IL-22⁺ Th22细胞比例，实时定量PCR法检测Th17转录因子维甲酸相关孤独核受体γt（RORγt）、Th22转录因子芳香烃受体（AhR）及Notch信号通路分子（包括Notch受体、Notch配体、Notch下游分子）mRNA相对表达量。纯化CD4⁺ T细胞，使用γ-分泌酶抑制剂（GSI）刺激培养，检测GSI刺激后细胞增殖、Th17和Th22细胞比例、IL-17和IL-22分泌、转录因子mRNA相对表达量变化。.结果IM组外周血单个核细胞中Notch1 和Notch2 mRNA的相对表达量分别为13.58±3.18、4.73±1.16，均明显高于对照组的1.09±0.12、1.07±0.15（均P < 0.001），而 Notch3和 Notch4 mRNA相对表达量在IM组和对照组之间的差异无统计学意义（P >0.05）。IM组Notch配体 DLL1和Jagged1 mRNA相对表达量、Notch信号下游分子Hes1、Hes5,和Hey1 mRNA相对表达量均高于对照组（均P < 0.001）。IM患者Th17和Th22细胞比例分别为5.03%±1.15%、4.48%±1.29%，均高于对照组的4.36%±0.82%、3.83%±0.55%（均P < 0.05）；血浆IL-17和IL-22水平分别为(301.1±53.82)pg/ml、(101.2±16.45)pg/ml，均高于对照组的(237.2±72.18)pg/ml、(84.75±11.83)pg/ml（均P < 0.001）；RORγt 和AhR mRNA相对表达量分别为1.25±0.22、1.21±0.12，均高于对照组的0.99±0.15、1.04±0.11（均P < 0.001）。CD4⁺ T细胞增殖水平、Th17细胞比例、IL-17分泌和RORγt mRNA相对表达量在无GSI刺激组和经GSI刺激组之间的差异无统计学意义（P >0.05）。经GSI刺激后Th22细胞比例、IL-22分泌和 AhR mRNA相对表达量较无GSI刺激降低（均P < 0.05）。.结论Notch信号通路通过AhR调控IM患者CD4⁺ T细胞分泌IL-22，Notch-AhR-Th22细胞通路可能参与IM发病。.