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Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy: Cancer Cell
They look at a new Ab that will bind JAG1 and inhibits bone metastasis. Also look at paclitaxel and cisplatin - say cisplatin upregulates jag1 on osteoblasts. Also note in the discussion that tumor cells make jag1 but that does not seem to be as effective.


"Here we demonstrate that various chemotherapy agents, including paclitaxel and cisplatin, induced Jagged1 expression in osteoblasts and MSCs, which feeds back to tumor cells to activate Notch signaling and promote chemoresistance. Administration of 15D11 into our in vitro 3D co-culture system or in various mouse models of bone metastasis significantly increased the sensitivity of tumor cells and bone metastasis to chemotherapy. Most strikingly, when chemotherapy was combined with 15D11, a nearly 100-fold reduction of bone metastasis burden was observed in our mouse model of bone metastasis. Thus, 15D11 represents a unique therapeutic agent capable of targeting both tumor-derived Jagged1 and chemotherapy-induced Jagged1 in osteoblasts, thus inhibiting multiple downstream Notch signaling events that are important for both the expansion of osteolytic lesions and chemoresistance of cancer cells in bone "
231_cells  sum1519  cisplatin  paclitaxel  chemoresistance  JAG1  Notch  bone_metastasis 
6 days ago by Segalllab
Huawei P11 might also have a notch • GSMArena
"Yordan":
<p>Huawei is preparing to launch its next flagship the P11 in February and first leaked firmware files suggest a surprise is on the way. According to XDA Developers, the Chinese manufacturer is going to introduce the phone with a notch on the front screen, similar to what we’ve seen in the iPhone X, Essential PH-1, and Sharp Aquos S2.

The overlay image comes from a reference in a configuration file that defines the “RoundCornerDisplay”. Multiple files are associated with this definition, all of them appearing to assist in avoiding drawing over parts of the screen to accommodate the unique display.

<img src="https://cdn.gsmarena.com/imgroot/news/17/12/huawei-notch/-728/gsmarena_000.jpg" width="100%" />

Another file has the word "notch" in its name “ro.config.hw_notch_size” with the value set to “258,84,411,27”. It might represent left, top, right and bottom offsets in moving screen content.</p>


I think the aim of this is just to make the screen look like the iPhone X because it's so striking, and in China - Huawei's biggest market - it's a status thing. See also: Huawei offering Force Touch (but then not following through).
huawei  notch 
7 days ago by charlesarthur
Overexpression of Pofut1 and activated Notch1 may be associated with poor prognosis in breast cancer
An antibody for activated Notch1 that works on FFPE sections - could try using that with the 231 and PyMT tumors (if it crossreacts with mouse)?

"Pofut1, located on chromosome 20q11.21, mainly produces an O-fucose modification on EGF-like repeats of a number of cellular surface and secreted proteins [14] ; [15]. To date, the most recognized substrates for Pofut1 are the EGF repeats with a C2-X(4–5)-[S/T]-C3 consensus, which was commonly presented in the extracellular domain of Notch [16]. Mechanistically, the O-fucosylation of Notch1 primarily initiated by Pofut1 is responsible for transferring the fucose to epidermal growth factor(EGF)-like repeats in the Notch receptor extracellular domain, which is necessary to sensitize the Notch1 ligand-receptor interaction [17], thereby acting in diverse biological activities.
Notch  nicd  immunostaining  pofut 
5 weeks ago by Segalllab
Excitable Dynamics and Yap-Dependent Mechanical Cues Drive the Segmentation Clock - ScienceDirect
Looking at oscillations during segmentation in drosophila, find that notch signaling lowers the threshold for excitability

"we demonstrate that PSM cells can exist in a quiescent state and can be switched to an oscillatory state in response to a cell density-dependent signal involving Notch and Yap signaling"
Notch  oscillations  YAP  segmentation 
5 weeks ago by Segalllab
The Cargo Protein MAP17 (PDZK1IP1) Regulates the Cancer Stem Cell Pool Activating the Notch Pathway by Abducting NUMB | Clinical Cancer Research
MAP17 can sequester NUMB to enhance notch signaling by prolonging nicd lifetimes

"Upon interaction with a ligand, Notch undergoes two proteolytic cleavages that result in signal transduction activation (53, 54). These cleavages result in the release of active NICD and its nuclear translocation. Thus, NICD joins a multiprotein transcriptional complex, integrating MAML1 and CSL1 (55, 56), required for Notch-mediated transcriptional regulation. Notch signaling persists until NICD is phosphorylated by CDK8 and targeted for proteasomal degradation (57). NUMB promotes the degradation of NICD following receptor activation, targeting it for proteasomal degradation, and preventing its translocation to the nucleus acting as a tumor suppressor (20, 58). Therefore, sequestration of NUMB allows for an increase in NICD and its transcriptional activity.

MAP17 overexpression, a protein not present in most somatic cells, but commonly deregulated in tumors (7, 9, 10), binds and sequestrates NUMB, activating Notch pathway and allowing nuclear NICD translocation. Therefore, through this mechanism, MAP17-expressing tumors activate Notch-dependent pro-proliferative genes and repress Notch-dependent tumor suppressor genes (Supplementary Fig. S8)."
Notch  numb 
5 weeks ago by Segalllab
The endothelial transcription factor ERG mediates Angiopoietin-1-dependent control of Notch signalling and vascular stability | Nature Communications
in endothelial cells ERG suppresses JAG1 and induces DLL4 in response to Ang1/Tie2 stimulation

"The Ang1-PI3K/Akt axis induces the formation of a transcriptional complex between β-catenin/NICD/RBP-J to enhance Dll4 expression and Notch signalling18,45. Notch and β-catenin are also expressed in nonvascular tissues, while ERG’s expression profile is restricted to the endothelium and a very limited number of other lineages. Thus ERG may confer endothelial-specificity to this pathway by mediating the Ang1/Tie2 signals to induce the formation of a β-catenin-NICD complex, which cooperatively induces Dll4 expression in the maturing and established endothelium. "
Notch  Tie2  ang1  dll4  JAG1 
5 weeks ago by Segalllab
react-community/react-native-safe-area-view: JS only version of SafeAreaView for supporting iPhone X safe area insets.
react-native-safe-area-view - JS only version of SafeAreaView for supporting iPhone X safe area insets.
notch  iphonex  react-native  safeareaview  views 
5 weeks ago by jimthedev
(429) https://twitter.com/i/web/status/927914954191200256
I don't believe in adapting design to . Rule of thumb, go with responsive web and you shall be let d…
notch  iphonex  from twitter_favs
5 weeks ago by oliver.turner
A cross-browser callout box using CSS border triangles - Peter Coles
This post describes how to use CSS border triangles (or slants) to successfully add a notch to a callout box—with no images and minimal markup—in a cross-browser way that even works in Internet Explorer 6.
css  popup  notch  howto  tutorial  blog  web  development 
6 weeks ago by aeng
Notch Shapes the Innate Immunophenotype in Breast Cancer | Cancer Discovery
Here they examine the role of JAG1 and Notch in 231 and other breast cancer cells - find that IL1B and CCL2 are JAG1/notch dependent. Propose a model where IL1B CCL2 attract macrophages which in turn then can activate TGFB.
231_cells  JAG1  Notch  IL1B  CCL2  TAMs 
6 weeks ago by Segalllab
Identification of Novel Breast Cancer Risk Loci | Cancer Research
sequenced notch genes but not jagged genes - notch3 is potentially correlated with increased risk
Notch  breast_cancer 
6 weeks ago by Segalllab

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