Human GPS1 blocking peptide

Background: Few studies have investigated whether the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score measured before resection of colorectal liver metastasis (CRLM), can predict postoperative survival. Patients and Methods: Sixty-three consecutive patients who underwent curative resection for CRLM were investigated. GPS was calculated on the basis of admission data as follows: patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminemia (<35 g/l) were allocated a GPS score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. Results: Significant factors concerning survival were the number of liver metastases (p = 0.0044), carcinoembryonic antigen level (p = 0.0191), GPS (p = 0.0029), grade of liver metastasis (p = 0.0033), and the number of lymph node metastases around the primary cancer (p = 0.0087). Multivariate analysis showed the two independent prognostic variables: liver metastases >= 3 (relative risk 2.83) and GPS1/2 (relative risk 3.07). Conclusions: GPS measured before operation and the number of liver metastases may be used as novel predictors of postoperative outcomes in patients who underwent curative resection for CRLM. Copyright (C) 2010 S. Karger AG, Basel

Pancreatic cancer remains one of the most lethal of all human malignancies with its incidence nearly equaling its mortality rate. Therefore, it's crucial to identify newer mechanism-based agents and targets to effectively manage pancreatic cancer. Plant-derived agents/drugs have historically been useful in cancer therapeutics. Sanguinarine is a plant alkaloid with anti-proliferative effects against cancers, including pancreatic cancer. This study was designed to determine the mechanism of sanguinarine's effects in pancreatic cancer with a hope to obtain useful information to improve the therapeutic options for the management of this neoplasm. We employed a quantitative proteomics approach to define the mechanism of sanguinarine's effects in human pancreatic cancer cells. Proteins from control and sanguinarine-treated pancreatic cancer cells were digested with trypsin, run by nano-LC/MS/MS, and identified with the help of Swiss-Prot database. Results from replicate injections were processed with the SIEVE software to identify proteins with differential expression. We identified 37 differentially expressed proteins (from a total of 3107), which are known to be involved in variety of cellular processes. Four of these proteins (IL33, CUL5, GPS1 and DUSP4) appear to occupy regulatory nodes in key pathways. Further validation by qRT-PCR and immunoblot analyses demonstrated that the dual specificity phosphatase-4 (DUSP4) was significantly upregulated by sanguinarine in BxPC-3 and MIA PaCa-2 cells. Sanguinarine treatment also caused down-regulation of HIF1 alpha and PCNA, and increased cleavage of PARP and Caspase-7. Taken together, sanguinarine appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of sanguinarine against pancreatic cancer.