MM41 is a quadruplex-interactive compound which binds strongly to the quadruplexes encoded in the promoter sequences of the BCL-2 and k-RAS genes, both of which are dis-regulated in many human pancreatic cancers.
Oncogene-directed increased expression of Nrf2 is a new mechanism for the activation of the Nrf2 antioxidant program, and is evident in primary cells and tissues of mice expressing K-Ras(G12D) and B-Raf(V619E), and in human pancreatic cancer.
The value of K-ras gene mutation for the detection of early pancreatic cancer and differentiation pancreatic cancer from chronic pancreatitis remains uncertain in clinical practice.
Similarly, in a mouse model of K-Ras-driven pancreatic cancer, loss of p27 accelerates tumor development and shortens survival, suggesting an important role for p27 in pancreatic tumorigenesis.
Loss of miR-143/145 expression is observed frequently in KRAS mutant pancreatic cancers, and restoration of these miRNAs abrogates tumorigenesis. miR-143/145 down-regulation requires the Ras-responsive element-binding protein (RREB1), which represses the miR-143/145 promoter.
The sensitivity, specificity, positive and negative predictive values of serum serum KRAS2 mutations for the diagnosis of pancreatic cancer were 47, 87, 85 and 52%, respectively.
K-Ras protein trafficking within the pancreatic cancer cells is effectively inhibited by the majority of statins; the inhibition is eliminated by isoprenoid intermediates of the mevalonate pathway.
Importantly, FGTI-2734 inhibited the growth of xenografts derived from four patients with pancreatic cancer with mutant KRAS (2G12D and 2 G12V) tumors.
K-ras gene point mutation and its style at codon 12 of human pancreatic cancer cell line Patu8988 were detected by using polymerase chain reaction with special sequence primers (PCR-SSP) and sequence analysis.
In an initial survey of KRAS2, TP53 and DPC4 genetic status in lethal metastatic pancreatic cancers, activating KRAS2 mutations were detected in 82% of cases and inactivating TP53 mutations in 55% of cases, consistent with rates of genetic alteration of these genes in early stage pancreatic cancers.
We studied the effects of nicotine administration on pancreatic cancer development in Kras(+/LSLG12Vgeo);Elas-tTA/tetO-Cre (Ela-KRAS) mice, Kras(+/LSLG12D);Trp53+/LSLR172H;Pdx-1-Cre (KPC) mice (which express constitutively active forms of KRAS), and C57/B6 mice.
These findings also showed that gene signatures related to KRAS dependency might be prospectively used to inform on decitabine sensitivity in a selected subset of patients with KRAS-mutated pancreatic cancer.
In this study we examined the potential of three intrinsically fluorescent benzo[α]phenoxazines or BPZs (R=Cl, CH3, H) to induce cytotoxic autophagy in chemo and apoptosis-resistant, KRAS and p53 mutated pancreatic cancer model cell line, MIAPaCa-2.
Western blot analysis revealed that LY-1816 markedly suppressed the Src signaling, and downregulated the expression of FOSL1; FOSL1 is an oncogene vulnerability in KRAS-driven pancreatic cancer.
RalA, RalB, and their major effectors RalBP1 and Sec5 were knocked down by stable expression of short hairpin RNAs in the K-Ras-dependent pancreatic cancer-derived cell line MIA PaCa-2.
Mutations in KRAS and p53 can be detected using genomic DNA from exosomes derived from pancreatic cancer cell lines and serum from patients with pancreatic cancer.
For PC cell lines with known KRAS mutations, single mutations were detected in 67% of homozygous cells but only 37.4% of heterozygous single cells, demonstrating that both coverage and allele dropout are important causes of mutation detection failure from single cells.