We used direct sequencing of polymerase chain reaction at 101 p53-positive and 10 p53-negative www.selleckchem.com/products/kpt-8602.html sites to sequence exons 5 to 8 of
p53 and then analyzed these results in concert with detailed histologic features.\n\nResults: Regardless of the degree of p53 overexpression, we detected p53 point mutations in all p53-positive lesions, including 22 noninvasive sites, 17 invasive areas, and 1 lymph node metastasis. No significant correlations were measured between specific p53 mutations and histologic features. Within individual tumors, the same p53 mutation was generally, but not always, detected in different areas in invasive and noninvasive lesions.\n\nConclusions: Our results demonstrate that p53 mutation is an early genetic event affecting a diversity of molecular pathways in pancreatic carcinogenesis and indicates a possibility of early diagnosis of pancreatic Selleckchem Ro-3306 carcinoma by detecting a few p53-positive cells obtained from the pancreatic fluid.”
“Despite malignant glioma vascularity, anti-angiogenic
therapy is largely ineffective. We hypothesize that efficacy of the antiangiogenic agent cediranib is synergistically enhanced in intracranial glioma via combination with the late-stage autophagy inhibitor quinacrine.\n\nRelative cerebral blood flow and volume (rCBF, rCBV), vascular permeability (K-trans), and tumor volume were assessed in intracranial 4C8 mouse glioma using a dual-bolus perfusion MRI approach. Tumor necrosis and tumor mean vessel density (MVD) were assessed immunohistologically. Autophagic vacuole accumulation and apoptosis were assessed via Western blot in 4C8 glioma in vitro.\n\nCediranib Roscovitine cost or quinacrine treatment alone did not alter tumor growth. Survival was only marginally improved by cediranib and
unchanged by quinacrine. In contrast, combined cediranib/quinacrine reduced tumor growth by 2-fold (P .05) and increased median survival by 2-fold, compared with untreated controls (P .05). Cediranib or quinacrine treatment alone did not significantly alter mean tumor rCBF or K-trans compared with untreated controls, while combined cediranib/quinacrine substantially reduced both (P .05), indicating potent tumor devascularization. MVD and necrosis were unchanged by cediranib or quinacrine treatment. In contrast, MVD was reduced by nearly 2-fold (P .01), and necrosis increased by 3-fold (P .05, one-tailed), in cediranib quinacrine treated vs untreated groups. Autophagic vacuole accumulation was induced by cediranib and quinacrine in vitro. Combined cediranib/quinacrine treatment under hypoxic conditions induced further accumulation and apoptosis.\n\nCombined cediranib/quinacrine treatment synergistically increased antivascular/antitumor efficacy in intracranial 4C8 mouse glioma, suggesting a promising and facile treatment strategy for malignant glioma. Modulations in the autophagic pathway may play a role in the increased efficacy.