Defining New Pancreatic Tumour Entities by Molecular Analysis

Mihaljevic, André L.; Espósito, Irene; Michalski, Christoph; Kleeff, Jörg; Friess, Helmut

doi:10.1159/000212081

Cited by 3 publications

(3 citation statements)

References 37 publications

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“…The latter histologic types correlate with expression of certain apomucins [44]. Similar to PanINs and MCNs, IPMNs show a graded progression form benign to malignant lesions correlating with the acquisition of distinct genetic alterations [45]. Again, K-RAS mutation is an early step in IPMN tumorigenesis [46,47], but contrary to PanIN, SMAD4 gene inactivation is infrequent in IPMN and is only seen in invasive components [48].…”

Section: Histopathology Of Pdac and Its Precursor Lesionsmentioning

confidence: 99%

Molecular biology, models, and histopathology of chronic pancreatitis and pancreatic cancer

et al. 2009

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Zusammenfassung. Grundlagen: Das duktale Adenokarzinom des Pankreas sowie die chronische Pankreatitis stellen zwei häufige und schwerwiegende Erkrankungen der Bauchspeicheldrüse dar. Auch wenn sich die Behandlung dieser Erkrankungen in den letzten Jahrzehnten deutlich verbessert hat, bleibt doch die Prognose in beiden Fällen schlecht, so dass die Entwicklung neuer Behandlungsoptionen notwendig erscheint. Dies wiederum setzt ein tieferes Verständnis der zu Grunde liegende Pathophysiologie, einschließlich der molekularen, genetischen und histopathologischen Veränderungen, voraus.Methodik: Ü bersichtsarbeit auf der Grundlage einer selektiven Literaturausarbeitung.Ergebnisse: Wesentliche Fortschritte im Bereich der Pankreasforschung haben unser Verständnis des duktalen Adenokarzinoms sowie der chronischen Pankreatitis vertieft. Die grundlegenden Erkenntnisse werden in diesem Artikel skizziert werden, mit besonderem Fokus auf den gemeinsamen pathophysiologischen Grundlagen beider Erkrankungen. Die Entwicklung des duktalen Adenokarzinoms aus Vorläuferläsionen ist in der Zwischenzeit im Detail beschrieben. Des Weiteren sind grundlegende genetische Veränderungen der Entwicklung und Ausbreitung des PDAC identifiziert worden. Viele molekulare Veränderungen sind jedoch in ihrer Bedeutung nicht genau bekannt oder noch nicht ausreichend untersucht worden. In der chronischen Pankreatitis haben neue Konzepte unser Verständnis der Erkrankung grundlegend verändert. Die Entdeckung und Charakterisierung von pankreatischen Sternzellen hat zu einem besseren Verständnis der Genese der Pankreasfibrose, eines der wesentlichen Charakteristika der chronischen Pankreatitis, beigetragen.Schlussfolgerungen: Unser wachsendes Wissen über die molekularen und histopathologischen Grundlagen des Pankreaskarzinoms sowie der chronischen Pankreatitis haben uns einen nie dagewesenen Einblick in die Entstehung dieser Erkrankungen ermöglicht.Summary. Background: Pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) represent frequent, and devastating diseases of the pancreas. Although the treatment for both conditions has improved over the past decades, overall prognosis remains poor necessitating the development of new treatment options, which in turn requires a deeper understanding of the underlying pathophysiology including genetic, molecular, and histopathologic changes occurring in both diseases.Methods: Review of the literature. Results: Significant progress has been made in the field of pancreatic research deepening our understanding of PDAC and CP development and maintenance. The landmark findings will be outlined in this article drawing attention to the common pathologic pathways of both diseases. On a histopathologic level, PDAC development from precursor lesions has been described in detail. Furthermore, genetic changes during PDAC initiation and maintenance have recently been discovered. However, the exact role of many molecular alterations found in PDAC remains unclear. In CP, new concepts have changed our understanding of t...

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Section: Histopathology Of Pdac and Its Precursor Lesionsmentioning

confidence: 99%

Molecular biology, models, and histopathology of chronic pancreatitis and pancreatic cancer

et al. 2009

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“…While individualized treatments have been used in medicine for many years, advances in cancer treatment have now generated a need to more precisely define and identify those patients who will derive the most benefit from new-targeted agents [19,20]. We succeeded in gene expression analysis and gene mutation analysis using the small amount samples by the newly developed 3D microarray system.…”

Section: Disscussionmentioning

confidence: 99%

A preliminary result of three-dimensional microarray technology to gene analysis with endoscopic ultrasound-guided fine-needle aspiration specimens and pancreatic juices

Nonogaki

Itoh

Kawashima

et al. 2010

J Exp Clin Cancer Res

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BackgroundAnalysis of gene expression and gene mutation may add information to be different from ordinary pathological tissue diagnosis. Since samples obtained endoscopically are very small, it is desired that more sensitive technology is developed for gene analysis. We investigated whether gene expression and gene mutation analysis by newly developed ultra-sensitive three-dimensional (3D) microarray is possible using small amount samples from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens and pancreatic juices.MethodsSmall amount samples from 17 EUS-FNA specimens and 16 pancreatic juices were obtained. After nucleic acid extraction, the samples were amplified with labeling and analyzed by the 3D microarray.ResultsThe analyzable rate with the microarray was 46% (6/13) in EUS-FNA specimens of RNAlater® storage, and RNA degradations were observed in all the samples of frozen storage. In pancreatic juices, the analyzable rate was 67% (4/6) in frozen storage samples and 20% (2/10) in RNAlater® storage. EUS-FNA specimens were classified into cancer and non-cancer by gene expression analysis and K-ras codon 12 mutations were also detected using the 3D microarray.ConclusionsGene analysis from small amount samples obtained endoscopically was possible by newly developed 3D microarray technology. High quality RNA from EUS-FNA samples were obtained and remained in good condition only using RNA stabilizer. In contrast, high quality RNA from pancreatic juice samples were obtained only in frozen storage without RNA stabilizer.

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“…Since then the evolution has been dramatic with progress in molecular biology [2,3], new possibilities for early diagnosis of pancreatic cancer [4,5], and lifeprolonging medical [6], curative surgical [7], and quality-improving palliative [8] treatments.…”

Section: Introductionmentioning

confidence: 99%

Pancreatic Carcinoma: Therapeutic Future Prospects

Andrén‐Sandberg¹,

Ansorge²,

Gilg³

2010

Viszeralmedizin

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In pancreatic cancer management progress has been made in the understanding of the disease on a molecular biological level and modalities for early diagnosis of pancreatic cancer have improved as well as the medical and surgical treatment strategies with curative, adjuvant and palliative aims. Realistic expectations for an earlier and more accurate diagnosis of pancreatic cancer – and thereby better treatment results – are constituted by the development of new blood tests and functional imaging. Adjuvants and neoadjuvants are presumed to be more effective and tolerable already in the near future, making the extended surgery more meaningful. On the same time, minimally invasive local treatments and laparoscopic resections are under development, eventually combined with localized growth factor treatment. One of the most important issue for improved clinical and oncological results is the centralization of complex resective procedures to few surgical centers, not due to the need of surgical skills but for an experienced team treatment approach during the operative and postoperative course. Finally, adjuvant treatment with pancreatic stem cells after curatively intended surgical resections is already on its way.

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Defining New Pancreatic Tumour Entities by Molecular Analysis

Cited by 3 publications

References 37 publications

Molecular biology, models, and histopathology of chronic pancreatitis and pancreatic cancer

Molecular biology, models, and histopathology of chronic pancreatitis and pancreatic cancer

A preliminary result of three-dimensional microarray technology to gene analysis with endoscopic ultrasound-guided fine-needle aspiration specimens and pancreatic juices

Pancreatic Carcinoma: Therapeutic Future Prospects

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