Pancreatic stellate cells in pancreatic cancer: In focus.

Pancreatic stellate cells are stromal cells that have multiple physiological functions such as the production of extracellular matrix, stimulation of amylase secretion, phagocytosis and immunity. In pancreatic cancer, stellate cells exhibit a different myofibroblastic-like morphology with the expression of alpha-smooth muscle actin, the activated form is engaged in several mechanisms that support tumorigenesis and cancer invasion and progression. In contrast to the aforementioned observations, eliminating the stromal cells that are positive for alpha-smooth muscle actin resulted in immune-evasion of the cancer cells and resulted in worse prognosis in animal models. Understanding the cancer-stromal signaling in pancreatic adenocarcinoma will provide novel strategies for therapy. Here we provide an updated review of studies that handle the topic "pancreatic stellate cells in cancer" and recent experimental approaches that can be the base for future directions in therapy.

Histone acetyltransferase inhibitors block neuroblastoma cell growth in vivo.

We have previously described novel histone acetyltransferase (HAT) inhibitors that block neuroblastoma cell growth in vitro. Here we show that two selected pyridoisothiazolone HAT inhibitors, PU139 and PU141, induce cellular histone hypoacetylation and inhibit growth of several neoplastic cell lines originating from different tissues. Broader in vitro selectivity profiling shows that PU139 blocks the HATs Gcn5, p300/CBP-associated factor (PCAF), CREB (cAMP response element-binding) protein (CBP) and p300, whereas PU141 is selective toward CBP and p300. The pan-inhibitor PU139 triggers caspase-independent cell death in cell culture. Both inhibitors block growth of SK-N-SH neuroblastoma xenografts in mice and the PU139 was shown to synergize with doxorubicin in vivo. The latter also reduces histone lysine acetylation in vivo at concentrations that block neoplastic xenograft growth. This is one of the very few reports on hypoacetylating agents with in vivo anticancer activity.

Genetics of inherited platelet disorders.

The current review describes inherited platelet disorders, illustrates their clinical phenotype and molecular genetic defects. Platelets are the key molecules mediating haemostasis via adhesion, activation and clot formation at the site of injury. The inherited platelet disorders can be classified according to their platelet defects: receptor/cytoskeleton defects, secretion disorder, and signal transduction defect. Patients with inherited thrombocytopathia present with mucous membrane bleedings (epistaxis, gingival bleeding) and may present with serious life threatening bleedings following surgery or trauma. Therefore, biochemical and molecular genetic characterization of inherited platelet disorders is important to understand these disorders and to support an efficient therapy.