Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells

Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial-mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk

High myeloperoxidase positive cell infiltration in colorectal cancer is an independent favorable prognostic factor

BACKGROUND Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG). METHODS A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491) was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets. RESULTS MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76). However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038) and validation (P = 0.002) sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15) and in both training (P = 0.048) and validation (P = 0.036) sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO-. CONCLUSIONS High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC

Internet of Things in Agricultural Innovation and Security

The agricultural Internet of Things (Ag-IoT) paradigm has tremendous potential in transparent integration of underground soil sensing, farm machinery, and sensor-guided irrigation systems with the complex social network of growers, agronomists, crop consultants, and advisors. The aim of the IoT in agricultural innovation and security chapter is to present agricultural IoT research and paradigm to promote sustainable production of safe, healthy, and profitable crop and animal agricultural products. This chapter covers the IoT platform to test optimized management strategies, engage farmer and industry groups, and investigate new and traditional technology drivers that will enhance resilience of the farmers to the socio-environmental changes. A review of state-of-the-art communication architectures and underlying sensing technologies and communication mechanisms is presented with coverage of recent advances in the theory and applications of wireless underground communications. Major challenges in Ag-IoT design and implementation are also discussed

Histone Deacetylase Inhibitors and Colorectal Cancer: what is new?

Colorectal cancer is the third most common cancer in humans. Cancer has always been regarded as a disease of genetic defects such as gene mutations and deletions, chromosomal abnormalities, which lead to the loss of function of tumor-suppressor genes and/or gain of function or hyperactivation of oncogenes. Modifications on chromatin are considered to be the result of the opposing activities of histone acetyltransferases and histone deacetylases, which affect gene expression. Targeting histone deacetylases, histone deacetylase inhibitors are promising agents, as in solid tumors they are characterized by relatively low toxicity profile and antiproliferative activities. In colorectal cancer, the current experience is mainly experimental but promising. Histone deacetylase inhibitors are currently being admitted as monotherapy or combination therapy either with the conventional chemotherapy or with other agents. Valproic acid combined with ionization may enhance tumor response. Vorinostat was the first drug of this group used in clinical trial in combination with conventional chemotherapy and managed to stabilize advanced colorectal cancer. Experimental results show that combination therapy of vorinostat and decitabine (DNA methyl transferase inhibitor) may have optimal results. However, patients with colorectal cancer need to be recruited in randomized clinical trials in order to evaluate the potential efficiency of these agents

Is routine MR cholangiopancreatography (MRCP) justified prior to cholecystectomy?

PURPOSE: We investigated routinely the bile ducts by magnetic resonance cholangiopancreaticography (MRCP) prior to cholecystectomy. The aim of this study was to analyze the rate of clinically inapparent common bile duct (CBD) stones, the predictive value of elevated liver enzymes for CBD stones, and the influence of the radiological results on the perioperative management. METHODS: In this prospective study, 465 patients were cholecystectomized within 18 months, mainly laparoscopically. Preoperative MRCP was performed in 454 patients. RESULTS: With MRCP screening, clinically silent CBD stones were found in 4%. Elevated liver enzymes have only a poor predictive value for the presence of CBD stones (positive predictive value, 21%; negative predictive value, 96%). Compared to the recent literature, the postoperative morbidity in this study was low (0 bile duct injury, 0.4% residual gallstones). CONCLUSIONS: Although MRCP is diagnostically useful in the perioperative management in some cases, its routine use in the DRG-era may not be justified due to the costs