Tesi etd-09202007-130531 |
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Tipo di tesi
Tesi di dottorato di ricerca
Autore
Chifenti, Barbara
Indirizzo email
barbchif@yahoo.it
URN
etd-09202007-130531
Titolo
Establishment and Characterization of Four New Human Pancreatic Cancer Cell Lines: Proposal for an in vitro Research Platform
Settore scientifico disciplinare
BIO/11
Corso di studi
ONCOLOGIA SPERIMENTALE E MOLECOLARE
Relatori
Relatore Dott. Cavazzana, Andrea
Relatore Dott.ssa Locci, Maria Teresa Fernanda
Relatore Dott.ssa Locci, Maria Teresa Fernanda
Parole chiave
- desmoplastic reaction
- in vitro model
- pancreatic cancer cell lines
- Pancreatic ductal adenocarcinoma (PDA)
Data inizio appello
17/04/2007
Consultabilità
Completa
Riassunto
Pancreatic ductal adenocarcinoma (PDA) is by far the most common tumor type of the exocrine pancreas, accounting from 85 to 90% of all pancreatic tumors. PDA is a rare disease affecting characteristically elderly individuals: approximately 80% of cases in fact occurs in patients older than 60, being patients below age 40 exceedingly rare.
PDA has the worst prognosis of all gastrointestinal malignancies, with an overall 5-year survival rate of less than 1% with a median survival of approximately 5 to 6 months. This high mortality rate is explained by its unusual aggressiveness, lack of responsiveness to chemotherapy and early occurrence of metastatic disease. At the time of diagnosis, in fact, the disease has often progressed to an advanced stage making the surgical resection an unpractical option.
To date, the molecular basis of this aggressive behaviour remains largely unclear and further investigations on pancreatic cancer biology are mandatory to provide new clues to develop strategies for prevention and treatment. A major difficulty in studying PDA biology is represented by the peculiar morphologic traits of the tumor. In fact PDA elicit a rich desmoplastic reaction so that tumor cells are generally largely spaced by reactive non tumor elements such as fibroblasts and inflammatory cells. For this purpose, tumor cell lines can represent an ideal tool as a pure renewable population of tumor cells useful to a variety of biologic and molecular experiments nevertheless most in vitro studies have been accomplished using a limited number of pancreatic cancer cell lines, which have been cultured in vitro for long time.
In the present study, we report the establishment and bio-molecular characterization of four new human pancreatic carcinoma cell lines (named PP78; PP109; PP117 and PP161) all derived from primary PDA.
We hereby describe the cell lines phenotypes, their specific genetic alteration of relevant tumor genes, in vitro growth characteristic as well as their unique DNA profile using a microsatellite fingerprinting analysis for identification purposes. Moreover their cytogenetic characteristics obtained by karyotype analysis are also provided.
PDA has the worst prognosis of all gastrointestinal malignancies, with an overall 5-year survival rate of less than 1% with a median survival of approximately 5 to 6 months. This high mortality rate is explained by its unusual aggressiveness, lack of responsiveness to chemotherapy and early occurrence of metastatic disease. At the time of diagnosis, in fact, the disease has often progressed to an advanced stage making the surgical resection an unpractical option.
To date, the molecular basis of this aggressive behaviour remains largely unclear and further investigations on pancreatic cancer biology are mandatory to provide new clues to develop strategies for prevention and treatment. A major difficulty in studying PDA biology is represented by the peculiar morphologic traits of the tumor. In fact PDA elicit a rich desmoplastic reaction so that tumor cells are generally largely spaced by reactive non tumor elements such as fibroblasts and inflammatory cells. For this purpose, tumor cell lines can represent an ideal tool as a pure renewable population of tumor cells useful to a variety of biologic and molecular experiments nevertheless most in vitro studies have been accomplished using a limited number of pancreatic cancer cell lines, which have been cultured in vitro for long time.
In the present study, we report the establishment and bio-molecular characterization of four new human pancreatic carcinoma cell lines (named PP78; PP109; PP117 and PP161) all derived from primary PDA.
We hereby describe the cell lines phenotypes, their specific genetic alteration of relevant tumor genes, in vitro growth characteristic as well as their unique DNA profile using a microsatellite fingerprinting analysis for identification purposes. Moreover their cytogenetic characteristics obtained by karyotype analysis are also provided.
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