Wnt, Notch and Hedgehog Activity in Chemo-Naive Tumors Collected During Staging of Esophageal Cancer Patients
Interrogation of Wnt, Notch, and Hedgehog Activity in Chemonaive Tumors Collected During the Staging Ultrasound Endoscopies of Patients Diagnosed With Esophageal Cancer
Cancer results when undifferentiated cells grow in an uncontrolled manner, crowding out normal cells, causing morbidity and ultimately mortality. the cancer stem cell theory suggests that most tumors undergo a process of differentiation through which a relatively rare cancer stem or progenitor cell (CSC) gives rise to more differentiated populations of cells (including transiently amplifying cells) comprising the bulk of the tumor. As a result of this cellular diversity, one or more cells within the tumor are likely to be resistant to therapy. Among cells resistant to a given therapy, only CSCs can repopulate the tumor. A key feature of this resistant subset of CSCs is that they repopulate a tumor resistant to the original intervention. The cellular programs driving the uncontrolled proliferation of many solid tumors result from aberrant activity of Wnt, Shh, and/or Notch signaling pathways in esc. Thus, therapies that down-regulate the activity of these fundamental pathways in CSCs will be effective in the treatment of cancer. The investigator's research program focuses on the elucidation of signaling mechanisms, control of cellular processes and discovery of small molecules that selectively target Wnt, Shh, and Notch signaling pathways that are fundamental to CSCs. Our preliminary results identified a novel Notch associated protein NACK that functions as a transcriptional co-activator of Notch. Moreover, Nack is expressed in human solid tumors and is required for cell survival and tumor growth in notch -dependent tumor cells.
The investigator's aim is to further interrogate the link between Notch and Nack.
Specific Aims:
- Identify and isolate the cancer stem cell populations from primary chemo naive esophageal tumor samples.
- Interrogate the status of the Notch,( the link between Notch and Nack), Wnt and Hedghog pathways in the chemo naive esophageal tumor as well as in specific cell populations, such as the CSC.
- Determine the degree of cross-talk between these pathways and which of these pathways is essential for the self renewal properties and tumorigenic properties of the esc population.
- Identify critical targets for therapeutic intervention in CSC populations.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Réel)
Contacts et emplacements
Lieux d'étude
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Florida
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Miami, Florida, États-Unis, 33136
- University of Miami
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
Méthode d'échantillonnage
Population étudiée
La description
Inclusion Criteria:
- Patients diagnosed with an esophageal cancer and scheduled for a standard of care endoscopic ultrasound.
- Patient must sign a consent to be a participant in this protocol.
Exclusion Criteria:
- Patients not diagnosed with an esophageal cancer.
- Patients that have undergone a previous staging endoscopic ultrasound.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
Intervention / Traitement |
|---|---|
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Patients with Esophageal Cancer
Tumor Biopsy via Ultrasound Endoscopy
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The staging ultrasound endoscopy is performed on patients previously diagnosed with esophageal cancer via diagnostic biopsy.
The staging ultrasound identifies affected lymph nodes and depth of tumor to the esophageal wall.
The tumor sampling is via a biopsy forcep (one pass to obtain 100 cells).
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
|
Percentage of samples with identifiable Notch, Wnt and Hedghog pathways in the chemo naive esophageal tumor as well as in cancer stem cell populations (CSC).
Délai: 24 months
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24 months
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Anthony Capobianco, MD, University of Miami
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 20120959
Informations sur les médicaments et les dispositifs, documents d'étude
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