Here's how DOI.ORG makes money* and how much!

*Please read our disclaimer before using our estimates.
Loading...

DOI . ORG {}

  1. Analyzed Page
  2. Matching Content Categories
  3. CMS
  4. Monthly Traffic Estimate
  5. How Does Doi.org Make Money
  6. Keywords
  7. Topics
  8. Questions
  9. Schema
  10. External Links
  11. Analytics And Tracking
  12. Libraries
  13. Hosting Providers
  14. CDN Services

We began analyzing https://link.springer.com/article/10.1007/s10549-012-2352-6, but it redirected us to https://link.springer.com/article/10.1007/s10549-012-2352-6. The analysis below is for the second page.

Title[redir]:
Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-α-independent mechanism | Breast Cancer Research and Treatment
Description:
X-linked inhibitor of apoptosis protein (XIAP), the most potent mammalian caspase inhibitor, has been associated with acquired therapeutic resistance in inflammatory breast cancer (IBC), an aggressive subset of breast cancer with an extremely poor survival rate. The second mitochondria-derived activator of caspases (Smac) protein is a potent antagonist of IAP proteins and the basis for the development of Smac mimetic drugs. Here, we report for the first time that bivalent Smac mimetic Birinapant induces cell death as a single agent in TRAIL-insensitive SUM190 (ErbB2-overexpressing) cells and significantly increases potency of TRAIL-induced apoptosis in TRAIL-sensitive SUM149 (triple-negative, EGFR-activated) cells, two patient tumor-derived IBC models. Birinapant has high binding affinity (nM range) for cIAP1/2 and XIAP. Using isogenic SUM149- and SUM190-derived cells with differential XIAP expression (SUM149 wtXIAP, SUM190 shXIAP) and another bivalent Smac mimetic (GT13402) with high cIAP1/2 but low XIAP binding affinity (K d > 1 μM), we show that XIAP inhibition is necessary for increasing TRAIL potency. In contrast, single agent efficacy of Birinapant is due to pan-IAP antagonism. Birinapant caused rapid cIAP1 degradation, caspase activation, PARP cleavage, and NF-κB activation. A modest increase in TNF-α production was seen in SUM190 cells following Birinapant treatment, but no increase occurred in SUM149 cells. Exogenous TNF-α addition did not increase Birinapant efficacy. Neutralizing antibodies against TNF-α or TNFR1 knockdown did not reverse cell death. However, pan-caspase inhibitor Q-VD-OPh reversed Birinapant-mediated cell death. In addition, Birinapant in combination or as a single agent decreased colony formation and anchorage-independent growth potential of IBC cells. By demonstrating that Birinapant primes cancer cells for death in an IAP-dependent manner, these findings support the development of Smac mimetics for IBC treatment.

Matching Content Categories {📚}

  • Science
  • Health & Fitness
  • Education

Content Management System {📝}

What CMS is doi.org built with?

Custom-built

No common CMS systems were detected on Doi.org, and no known web development framework was identified.

Traffic Estimate {📈}

What is the average monthly size of doi.org audience?

🌠 Phenomenal Traffic: 5M - 10M visitors per month


Based on our best estimate, this website will receive around 8,426,036 visitors per month in the current month.

check SE Ranking
check Ahrefs
check Similarweb
check Ubersuggest
check Semrush

How Does Doi.org Make Money? {💸}

We don't see any clear sign of profit-making.

Not all websites focus on profit; some are designed to educate, connect people, or share useful tools. People create websites for numerous reasons. And this could be one such example. Doi.org has a secret sauce for making money, but we can't detect it yet.

Keywords {🔍}

cancer, article, google, scholar, pubmed, cas, apoptosis, breast, cells, inhibitor, smac, cell, inflammatory, res, protein, xiap, mimetic, birinapant, devi, xlinked, death, usa, trail, lyerly, ciap, wang, treatment, allensworth, sum, access, van, research, induces, nfkappab, mol, smacdiablo, duke, privacy, cookies, content, gayathri, ibc, iap, clin, aird, treat, biol, human, university, information,

Topics {✒️}

american cancer society-rsg-08-290-01-cce smac mimetics—small-molecule antagonists apo-2l/trail-induced apoptosis month download article/chapter smac/diablo-induced cell death smac mimetic-mediated sensitization smac-mimetic-induced apoptosis structure-based computational screening tnf-α-independent mechanism apoptosis inducer smac/diablo smac/diablo protein expression small-molecular weight inhibitor anticancer drug-induced apoptosis nf-kappab-dependent manner cellular flice-inhibitory protein bivalent smac mimetic anchorage-independent growth potential induce tnfalpha-dependent apoptosis tnf-alpha-independent apoptosis exogenous tnf-α addition induced nf-kappab nuclear factor kappab full article pdf breast cancer research pan-iap antagonism smac mimetic drugs smac mimetic enables nf-kappab activation related subjects activate nf-kappab privacy choices/manage cookies trail induces apoptosis nf-κb activation trail-induced apoptosis temozolomide-induced apoptosis gemcitabine-induced apoptosis gene expression profiling lentiviral-mediated delivery duke university chancellor x-linked inhibitor enhances chemotherapy sensitivity anchorage independent growth anchorage-independent growth inflammatory breast cancer inflammatory breast cancer small interfering rna inflammatory breast carcinoma human cancer cells apoptosis protein expression tnfalpha-dependent apoptosis

Questions {❓}

  • Anderson WF, Chu KC, Chang S (2003) Inflammatory breast carcinoma and noninflammatory locally advanced breast carcinoma: distinct clinicopathologic entities?
  • Wu H, Tschopp J, Lin SC (2007) Smac mimetics and TNFalpha: a dangerous liaison?

Schema {🗺️}

WebPage:
      mainEntity:
         headline:Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-α-independent mechanism
         description:X-linked inhibitor of apoptosis protein (XIAP), the most potent mammalian caspase inhibitor, has been associated with acquired therapeutic resistance in inflammatory breast cancer (IBC), an aggressive subset of breast cancer with an extremely poor survival rate. The second mitochondria-derived activator of caspases (Smac) protein is a potent antagonist of IAP proteins and the basis for the development of Smac mimetic drugs. Here, we report for the first time that bivalent Smac mimetic Birinapant induces cell death as a single agent in TRAIL-insensitive SUM190 (ErbB2-overexpressing) cells and significantly increases potency of TRAIL-induced apoptosis in TRAIL-sensitive SUM149 (triple-negative, EGFR-activated) cells, two patient tumor-derived IBC models. Birinapant has high binding affinity (nM range) for cIAP1/2 and XIAP. Using isogenic SUM149- and SUM190-derived cells with differential XIAP expression (SUM149 wtXIAP, SUM190 shXIAP) and another bivalent Smac mimetic (GT13402) with high cIAP1/2 but low XIAP binding affinity (K d > 1 μM), we show that XIAP inhibition is necessary for increasing TRAIL potency. In contrast, single agent efficacy of Birinapant is due to pan-IAP antagonism. Birinapant caused rapid cIAP1 degradation, caspase activation, PARP cleavage, and NF-κB activation. A modest increase in TNF-α production was seen in SUM190 cells following Birinapant treatment, but no increase occurred in SUM149 cells. Exogenous TNF-α addition did not increase Birinapant efficacy. Neutralizing antibodies against TNF-α or TNFR1 knockdown did not reverse cell death. However, pan-caspase inhibitor Q-VD-OPh reversed Birinapant-mediated cell death. In addition, Birinapant in combination or as a single agent decreased colony formation and anchorage-independent growth potential of IBC cells. By demonstrating that Birinapant primes cancer cells for death in an IAP-dependent manner, these findings support the development of Smac mimetics for IBC treatment.
         datePublished:2012-12-07T00:00:00Z
         dateModified:2012-12-07T00:00:00Z
         pageStart:359
         pageEnd:371
         sameAs:https://doi.org/10.1007/s10549-012-2352-6
         keywords:
            Smac/DIABLO
            Inhibitor of apoptosis protein (IAP)
            TRAIL
            Inflammatory breast cancer (IBC)
            TNF- α
            Oncology
         image:
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig1_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig2_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig3_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig4_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig5_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig6_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig7_HTML.gif
         isPartOf:
            name:Breast Cancer Research and Treatment
            issn:
               1573-7217
               0167-6806
            volumeNumber:137
            type:
               Periodical
               PublicationVolume
         publisher:
            name:Springer US
            logo:
               url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
               type:ImageObject
            type:Organization
         author:
               name:Jennifer L. Allensworth
               affiliation:
                     name:Duke University Medical Center
                     address:
                        name:Department of Surgery, Duke University Medical Center, Durham, USA
                        type:PostalAddress
                     type:Organization
                     name:Duke University Medical Center
                     address:
                        name:Department of Pathology, Duke University Medical Center, Durham, USA
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Scott J. Sauer
               affiliation:
                     name:Duke University Medical Center
                     address:
                        name:Department of Surgery, Duke University Medical Center, Durham, USA
                        type:PostalAddress
                     type:Organization
               type:Person
               name:H. Kim Lyerly
               affiliation:
                     name:Duke University Medical Center
                     address:
                        name:Department of Surgery, Duke University Medical Center, Durham, USA
                        type:PostalAddress
                     type:Organization
                     name:DUMC Duke University Medical Center
                     address:
                        name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Michael A. Morse
               affiliation:
                     name:Duke University Medical Center
                     address:
                        name:Department of Medicine, Duke University Medical Center, Durham, USA
                        type:PostalAddress
                     type:Organization
                     name:DUMC Duke University Medical Center
                     address:
                        name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Gayathri R. Devi
               affiliation:
                     name:Duke University Medical Center
                     address:
                        name:Department of Surgery, Duke University Medical Center, Durham, USA
                        type:PostalAddress
                     type:Organization
                     name:Duke University Medical Center
                     address:
                        name:Department of Pathology, Duke University Medical Center, Durham, USA
                        type:PostalAddress
                     type:Organization
                     name:DUMC Duke University Medical Center
                     address:
                        name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
         isAccessibleForFree:
         hasPart:
            isAccessibleForFree:
            cssSelector:.main-content
            type:WebPageElement
         type:ScholarlyArticle
      context:https://schema.org
ScholarlyArticle:
      headline:Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-α-independent mechanism
      description:X-linked inhibitor of apoptosis protein (XIAP), the most potent mammalian caspase inhibitor, has been associated with acquired therapeutic resistance in inflammatory breast cancer (IBC), an aggressive subset of breast cancer with an extremely poor survival rate. The second mitochondria-derived activator of caspases (Smac) protein is a potent antagonist of IAP proteins and the basis for the development of Smac mimetic drugs. Here, we report for the first time that bivalent Smac mimetic Birinapant induces cell death as a single agent in TRAIL-insensitive SUM190 (ErbB2-overexpressing) cells and significantly increases potency of TRAIL-induced apoptosis in TRAIL-sensitive SUM149 (triple-negative, EGFR-activated) cells, two patient tumor-derived IBC models. Birinapant has high binding affinity (nM range) for cIAP1/2 and XIAP. Using isogenic SUM149- and SUM190-derived cells with differential XIAP expression (SUM149 wtXIAP, SUM190 shXIAP) and another bivalent Smac mimetic (GT13402) with high cIAP1/2 but low XIAP binding affinity (K d > 1 μM), we show that XIAP inhibition is necessary for increasing TRAIL potency. In contrast, single agent efficacy of Birinapant is due to pan-IAP antagonism. Birinapant caused rapid cIAP1 degradation, caspase activation, PARP cleavage, and NF-κB activation. A modest increase in TNF-α production was seen in SUM190 cells following Birinapant treatment, but no increase occurred in SUM149 cells. Exogenous TNF-α addition did not increase Birinapant efficacy. Neutralizing antibodies against TNF-α or TNFR1 knockdown did not reverse cell death. However, pan-caspase inhibitor Q-VD-OPh reversed Birinapant-mediated cell death. In addition, Birinapant in combination or as a single agent decreased colony formation and anchorage-independent growth potential of IBC cells. By demonstrating that Birinapant primes cancer cells for death in an IAP-dependent manner, these findings support the development of Smac mimetics for IBC treatment.
      datePublished:2012-12-07T00:00:00Z
      dateModified:2012-12-07T00:00:00Z
      pageStart:359
      pageEnd:371
      sameAs:https://doi.org/10.1007/s10549-012-2352-6
      keywords:
         Smac/DIABLO
         Inhibitor of apoptosis protein (IAP)
         TRAIL
         Inflammatory breast cancer (IBC)
         TNF- α
         Oncology
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig1_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig2_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig3_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig4_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig5_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig6_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10549-012-2352-6/MediaObjects/10549_2012_2352_Fig7_HTML.gif
      isPartOf:
         name:Breast Cancer Research and Treatment
         issn:
            1573-7217
            0167-6806
         volumeNumber:137
         type:
            Periodical
            PublicationVolume
      publisher:
         name:Springer US
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Jennifer L. Allensworth
            affiliation:
                  name:Duke University Medical Center
                  address:
                     name:Department of Surgery, Duke University Medical Center, Durham, USA
                     type:PostalAddress
                  type:Organization
                  name:Duke University Medical Center
                  address:
                     name:Department of Pathology, Duke University Medical Center, Durham, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Scott J. Sauer
            affiliation:
                  name:Duke University Medical Center
                  address:
                     name:Department of Surgery, Duke University Medical Center, Durham, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:H. Kim Lyerly
            affiliation:
                  name:Duke University Medical Center
                  address:
                     name:Department of Surgery, Duke University Medical Center, Durham, USA
                     type:PostalAddress
                  type:Organization
                  name:DUMC Duke University Medical Center
                  address:
                     name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Michael A. Morse
            affiliation:
                  name:Duke University Medical Center
                  address:
                     name:Department of Medicine, Duke University Medical Center, Durham, USA
                     type:PostalAddress
                  type:Organization
                  name:DUMC Duke University Medical Center
                  address:
                     name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Gayathri R. Devi
            affiliation:
                  name:Duke University Medical Center
                  address:
                     name:Department of Surgery, Duke University Medical Center, Durham, USA
                     type:PostalAddress
                  type:Organization
                  name:Duke University Medical Center
                  address:
                     name:Department of Pathology, Duke University Medical Center, Durham, USA
                     type:PostalAddress
                  type:Organization
                  name:DUMC Duke University Medical Center
                  address:
                     name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
      isAccessibleForFree:
      hasPart:
         isAccessibleForFree:
         cssSelector:.main-content
         type:WebPageElement
["Periodical","PublicationVolume"]:
      name:Breast Cancer Research and Treatment
      issn:
         1573-7217
         0167-6806
      volumeNumber:137
Organization:
      name:Springer US
      logo:
         url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
         type:ImageObject
      name:Duke University Medical Center
      address:
         name:Department of Surgery, Duke University Medical Center, Durham, USA
         type:PostalAddress
      name:Duke University Medical Center
      address:
         name:Department of Pathology, Duke University Medical Center, Durham, USA
         type:PostalAddress
      name:Duke University Medical Center
      address:
         name:Department of Surgery, Duke University Medical Center, Durham, USA
         type:PostalAddress
      name:Duke University Medical Center
      address:
         name:Department of Surgery, Duke University Medical Center, Durham, USA
         type:PostalAddress
      name:DUMC Duke University Medical Center
      address:
         name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
         type:PostalAddress
      name:Duke University Medical Center
      address:
         name:Department of Medicine, Duke University Medical Center, Durham, USA
         type:PostalAddress
      name:DUMC Duke University Medical Center
      address:
         name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
         type:PostalAddress
      name:Duke University Medical Center
      address:
         name:Department of Surgery, Duke University Medical Center, Durham, USA
         type:PostalAddress
      name:Duke University Medical Center
      address:
         name:Department of Pathology, Duke University Medical Center, Durham, USA
         type:PostalAddress
      name:DUMC Duke University Medical Center
      address:
         name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Jennifer L. Allensworth
      affiliation:
            name:Duke University Medical Center
            address:
               name:Department of Surgery, Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
            name:Duke University Medical Center
            address:
               name:Department of Pathology, Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
      name:Scott J. Sauer
      affiliation:
            name:Duke University Medical Center
            address:
               name:Department of Surgery, Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
      name:H. Kim Lyerly
      affiliation:
            name:Duke University Medical Center
            address:
               name:Department of Surgery, Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
            name:DUMC Duke University Medical Center
            address:
               name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
      name:Michael A. Morse
      affiliation:
            name:Duke University Medical Center
            address:
               name:Department of Medicine, Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
            name:DUMC Duke University Medical Center
            address:
               name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
      name:Gayathri R. Devi
      affiliation:
            name:Duke University Medical Center
            address:
               name:Department of Surgery, Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
            name:Duke University Medical Center
            address:
               name:Department of Pathology, Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
            name:DUMC Duke University Medical Center
            address:
               name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Surgery, Duke University Medical Center, Durham, USA
      name:Department of Pathology, Duke University Medical Center, Durham, USA
      name:Department of Surgery, Duke University Medical Center, Durham, USA
      name:Department of Surgery, Duke University Medical Center, Durham, USA
      name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
      name:Department of Medicine, Duke University Medical Center, Durham, USA
      name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
      name:Department of Surgery, Duke University Medical Center, Durham, USA
      name:Department of Pathology, Duke University Medical Center, Durham, USA
      name:Duke Cancer Institute, DUMC Duke University Medical Center, Durham, USA
WebPageElement:
      isAccessibleForFree:
      cssSelector:.main-content

External Links {🔗}(223)

Analytics and Tracking {📊}

  • Google Tag Manager

Libraries {📚}

  • Clipboard.js
  • Prism.js

Emails and Hosting {✉️}

Mail Servers:

  • mx.zoho.eu
  • mx2.zoho.eu
  • mx3.zoho.eu

Name Servers:

  • josh.ns.cloudflare.com
  • zita.ns.cloudflare.com

CDN Services {📦}

  • Crossref

4.27s.