Differential role of Hedgehog signaling in human pancreatic (patho-) physiology: An up to date review.

Since the discovery of the Hedgehog (Hh) pathway in drosophila melanogaster, our knowledge of the role of Hh in embryonic development, inflammation, and cancerogenesis in humans has dramatically increased over the last decades. This is the case especially concerning the pancreas, however, real therapeutic breakthroughs are missing until now. In general, Hh signaling is essential for pancreatic organogenesis, development, and tissue maturation.

Back to the start: Evaluation of prognostic markers in gastrointestinal stromal tumors.

The aim of this study was to provide a standardized risk stratification model for gastrointestinal stromal tumors (GISTs) based on tumor localization, tumor size, involved lymph nodes and metastases, as well as mitotic activity and other morphological and molecular markers, in order to improve the risk evaluation scheme for recurrence, metastatic spread and survival for patients with GIST. A total of 201 cases of patients with GIST were investigated according to standardized morphological markers, including nuclear pleomorphism, tumor cell necrosis, mucosal infiltration, ulceration, skeinoid fibers and growth pattern. In addition, all cases were immunohistochemically analyzed using a tissue microarray platform for various markers of differentiation (CD34, CD44, CD117, desmin, discovered on GIST 1, platelet-derived growth factor receptor α, S-100 and smooth muscle actin) and proliferation (B-cell lymphoma 2, P16, P53, phosphohistone H3 and Ki-67).

Autophagy-related cell death by pan-histone deacetylase inhibition in liver cancer.

Autophagy is a homeostatic, catabolic degradation process and cell fate essential regulatory mechanism. Protracted autophagy triggers cell death; its aberrant function is responsible for several malignancies. Panobinostat, a potent pan-deacetylase inhibitor, causes endoplasmic reticulum stress-induced cell death.

Role of histone deacetylases in pancreas: Implications for pathogenesis and therapy.

In the last years, our knowledge of the pathogenesis in acute and chronic pancreatitis (AP/CP) as well as in pancreatic cancerogenesis has significantly diversified. Nevertheless, the medicinal therapeutic options are still limited and therapeutic success and patient outcome are poor. Epigenetic deregulation of gene expression is known to contribute to development and progression of AP and CP as well as of pancreatic cancer.

Endoplasmic Reticulum Stress in Pancreatic Neuroendocrine Tumors is Linked to Clinicopathological Parameters and Possible Epigenetic Regulations.

Background: Endoplasmic reticulum (ER) stress is a highly-conserved cellular defense mechanism in response to perturbations of ER function. The role of ER stress in pancreatic neuroendocrine tumors (pNET) still remains unclear.

Materials And Methods: We analyzed the protein expression pattern of the four key players of ER stress, (chaperone binding imunoglobluin protein (BiP), C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4) and caspase 4) as well as histone deacetylases (HDACs) by a tissue microarray (TMA) of 49 human pNET resected between 1997 and 2013 following, extensive clinicopathological characterization.