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1.
Biol. Res ; 53: 13, 2020. tab, graf
Article Dans Anglais | LILACS | ID: biblio-1100919

Résumé

BACKGROUND: Gallbladder cancer (GBC) is the most common tumor of the biliary tract. The incidence of GBC shows a large geographic variability, being particularly frequent in Native American populations. In Chile, GBC represents the second cause of cancer-related death among women. We describe here the establishment of three novel cell lines derived from the ascitic fluid of a Chilean GBC patient, who presented 46% European, 36% Mapuche, 12% Aymara and 6% African ancestry. RESULTS: After immunocytochemical staining of the primary cell culture, we isolated and comprehensively characterized three independent clones (PUC-GBC1, PUC-GBC2 and PUC-GBC3) by short tandem repeat DNA profiling and RNA sequencing as well as karyotype, doubling time, chemosensitivity, in vitro migration capability and in vivo tumorigenicity assay. Primary culture cells showed high expression of CK7, CK19, CA 19-9, MUC1 and MUC16, and negative expression of mesothelial markers. The three isolated clones displayed an epithelial phenotype and an abnormal structure and number of chromosomes. RNA sequencing confirmed the increased expression of cytokeratin and mucin genes, and also of TP53 and ERBB2 with some differences among the three cells lines, and revealed a novel exonic mutation in NF1. The PUC-GBC3 clone was the most aggressive according to histopathological features and the tumorigenic capacity in NSG mice. CONCLUSIONS: The first cell lines established from a Chilean GBC patient represent a new model for studying GBC in patients of Native American descent.


Sujets)
Humains , Animaux , Mâle , Adulte d'âge moyen , Antigènes glycanniques associés aux tumeurs/génétique , Indien Amérique Sud/génétique , Tumeurs de la vésicule biliaire/génétique , Liquide d'ascite/métabolisme , Cellules cancéreuses en culture , Tests de cancérogénicité , Chili , Profilage d'ADN , Protéine p53 suppresseur de tumeur/génétique , Cisplatine/pharmacologie , Souris de lignée NOD , Clones cellulaires/effets des médicaments et des substances chimiques , Clones cellulaires/métabolisme , Analyse de séquence d'ARN , Récepteur ErbB-2/génétique , Gènes erbB-2/génétique , Analyse de profil d'expression de gènes , Lignée cellulaire tumorale/effets des médicaments et des substances chimiques , Lignée cellulaire tumorale/métabolisme , Désoxycytidine/analogues et dérivés , Désoxycytidine/pharmacologie , Cellules épithéliales/métabolisme , Kératine-19/génétique , Kératine-7/génétique , Carcinogenèse/génétique , Tumeurs de la vésicule biliaire/métabolisme , Antinéoplasiques/pharmacologie
2.
Indian J Med Sci ; 2009 Apr; 63(4): 152-62
Article Dans Anglais | IMSEAR | ID: sea-67016

Résumé

Background : Normal breast ducts contain at least 3 types of epithelial cells: luminal (glandular) cells, basal/myoepithelial cells and stem cells. Myoepithelial and luminal epithelia can be distinguished by their different cytokeratin expression patterns. The aim of this study is to evaluate the expression of some prognostic biomarkers (ER, PR and HER2), as well as histological grading and lymph node status in cytokeratin-based groups of breast cancer. Objective: To evaluate the correlation between expression of basal and luminal markers and hormonal receptors, HER2/neu, age, grade and lymph node status in breast-invasive ductal carcinoma. Materials and Methods : Sixty-seven formalin-fixed and paraffin-embedded breast cancer specimens (of invasive ductal carcinoma, 'NOS' type) which had already been studied for ER, PR and HER2/neu were selected. Data concerning age, tumor grade and lymph node status were also obtained from archives. Expression of basal (CK5/6) and luminal (CK7) cytokeratins was detected by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of stained cells. Results : We categorized the cases into 3 distinct phenotype groups: pure luminal, basal phenotype and null. Pure basal, mixed basal and luminal groups were classified as expressing a basal phenotype. There was a significant difference in the ER and/or PR expression between those 3 groups and a significant association between ER and/or PR negativity and basal phenotype expression. There was no significant difference in HER2/neu expression, age of the patients, tumor grade and lymph node status between the 3 cytokeratin-based groups and no significant association between lymph node status and basal phenotype expression. Conclusion : We found that to gain a real association between basal phenotype and prognostic markers, we should use a cocktail or a panel of different biomarkers to correctly determine basal-like phenotype of breast cancers. This approach guarantees more concordance with gene expression-based studies.


Sujets)
Tumeurs du sein/diagnostic , Carcinome canalaire/diagnostic , Carcinome canalaire/génétique , Femelle , Expression des gènes , Humains , Kératine-5/génétique , Kératine-6/génétique , Kératine-7/génétique , Adulte d'âge moyen , Phénotype , Tumeurs du sein/génétique , Pronostic , Récepteurs ErbB/génétique , Récepteurs des oestrogènes/génétique , Récepteurs à la progestérone/génétique , Marqueurs biologiques tumoraux/génétique
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