Immune-Based Therapies and the Role of Microsatellite Instability in Pancreatic Cancer

Pancreatic cancer is one of the most aggressive malignancies with limited treatment options thus resulting in high morbidity and mortality. Among all cancers, with a five-year survival rates of only 2–9%, pancreatic cancer holds the worst prognostic outcome for patients. To improve the overall survival, an earlier diagnosis and stratification of cancer patients for personalized treatment options are urgent needs. A minority of pancreatic cancers belong to the spectrum of Lynch syndrome-associated cancers and are characterized by microsatellite instability (MSI). MSI is a consequence of defective mismatch repair protein functions and it has been well characterized in other gastrointestinal tumors such as colorectal and gastric cancer. In the latter, high levels of MSI are linked to a better prognosis and to an increased benefit to immune-based therapies. Therefore, the same therapies could offer an opportunity of treatment for pancreatic cancer patients with MSI. In this review, we summarize the current knowledge about immune-based therapies and MSI in pancreatic cancer

MMP-13, p53 in the Progression of Malignant Peripheral Nerve Sheath Tumors

Malignant peripheral nerve sheath tumors (MPNST) are sarcomas with poor prognosis, limited treatment options. Factors contributing to tumor progression are largely unknown. We therefore examined MPNST from 22 neurofibromatosis type 1 (NF1) patients, 14 nonNF1 patients, 14 neurofibroma patients for matrix metalloproteinase 13 (MMP-13) expression. Because wild-type, mutant p53 were shown to differentially regulate MMP-13 expression, TP53 status, protein levels were also determined. MMP-13 expression was detected in 58% of MPNST, was significantly associated with recurrent MPNST (P = .019). p53 was observed in 78% of MPNST, was found to be strongly associated with MMP-13 expression (P = .005). In contrast, 14 neurofibromas lacked MMP-13, p53 expressions. TP53 mutations were found in only 11% of MPNST, were associated with high tumor grades (P = .029). No significant association between mutant TP53, MMP-13 was observed, indicating that other factors drive MMP-13 expression in MPNST. The presence of metastasis was linked to p53Pro72 polymorphism (P= .041), shorter survival. In summary, our data suggest that MMP-13 expression in nerve sheath tumors is coupled with malignant progression. Therefore, MMP-13 may serve as a marker for progression, as a therapeutic target

Intrinsically radiopaque iodine-containing polyvinyl alcohol as a liquid embolic agent: evaluation in experimental wide-necked aneurysms

OBJECT: To evaluate iodine-containing polyvinyl alcohol (I-PVA) as a precipitating liquid embolic agent, implant characteristics--including radiopacity, setting behavior, and biocompatibility--were studied in an aneurysm model in swine. METHODS: Twelve broad-based carotid artery (CA) sidewall aneurysms were surgically constructed in six pigs. Iodine-containing polyvinyl alcohol dissolved in dimethyl sulfoxide (DMSO) was injected during temporary balloon occlusion bridging the aneurysm neck. Control angiography as well as multidetector row computerized tomography (CT) angiography was performed after 4 weeks. Harvested aneurysms were investigated histopathologically and by 3-tesla high-field magnetic resonance (MR) imaging. The mean degree of aneurysm occlusion achieved was 96%. In two aneurysms a minimal protrusion of I-PVA into the CA lumen was observed. During one embolization, leakage of the liquid embolic agent due to DMSO-induced damage of the microcatheter resulted in CA occlusion. Aneurysms embolized with I-PVA could be discriminated clearly from the parent artery on CT angiograms because there was no beam-hardening artifact. High-field MR imaging allowed a detailed depiction of the liquid embolic distribution within the aneurysm. Histologically, a mild to moderate inflammatory response was found in successfully embolized aneurysms, and the polymer mass was frequently covered by a membrane of fibroblasts and endothelial cells. CONCLUSIONS: Iodine-containing polyvinyl alcohol is a ready-to-use liquid embolic agent clearly visible under fluoroscopy; additives are not required. The setting behavior allows for controlled delivery in aneurysm cavities. Histological studies performed 4 weeks after embolization revealed no sign of toxic tissue response to the liquid embolic agent. Overall, I-PVA exhibits interesting implant characteristics in that radiopaque admixtures are not necessary, thus allowing for artifact-free evaluation of treated aneurysms by using CT Ad MR angiography