Oxidative Stress, Inflammation, and Cancer: How Are They Linked?

Elevated rates of reactive oxygen species (ROS) have been detected in almost all cancers, where they promote many aspects of tumour development and progression. However, tumour cells also express increased levels of antioxidant proteins to detoxify from ROS, suggesting that a delicate balance of intracellular ROS levels is required for cancer cell function. Further, the radical generated, the location of its generation, as well as the local concentration is important for the cellular functions of ROS in cancer. A challenge for novel therapeutic strategies will be the fine tuning of intracellular ROS signalling to effectively deprive cells from ROS-induced tumour promoting events, towards tipping the balance to ROS-induced apoptotic signalling. Alternatively, therapeutic antioxidants may prevent early events in tumour development, where ROS are important. However, to effectively target cancer cells specific ROS-sensing signalling pathways that mediate the diverse stress-regulated cellular functions need to be identified. This review discusses the generation of ROS within tumour cells, their detoxification, their cellular effects, as well as the major signalling cascades they utilize, but also provides an outlook on their modulation in therapeutics.

/pdf/reactive-oxygen-species-in-cancer-2cc2eau8py.pdf

Reactive oxygen species in cancer

https://home.ccr.cancer.gov/ncifdaproteomics/pdf/CancerCell-PanIN.pdf

Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse

Two-dimensional gel electrophoresis (2-DE) with immobilized pH gradients (IPGs) combined with protein identification by mass spectrometry (MS) is currently the workhorse for proteomics. In spite of promising alternative or complementary technologies (e.g. multidimensional protein identification technology, stable isotope labelling, protein or antibody arrays) that have emerged recently, 2-DE is currently the only technique that can be routinely applied for parallel quantitative expression profiling of large sets of complex protein mixtures such as whole cell lysates. 2-DE enables the separation of complex mixtures of proteins according to isoelectric point (pI), molecular mass (Mr), solubility, and relative abundance. Furthermore, it delivers a map of intact proteins, which reflects changes in protein expression level, isoforms or post-translational modifications. This is in contrast to liquid chromatography-tandem mass spectrometry based methods, which perform analysis on peptides, where Mr and pI information is lost, and where stable isotope labelling is required for quantitative analysis. Today's 2-DE technology with IPGs (Gorg et al., Electrophoresis 2000, 21, 1037-1053), has overcome the former limitations of carrier ampholyte based 2-DE (O'Farrell, J. Biol. Chem. 1975, 250, 4007-4021) with respect to reproducibility, handling, resolution, and separation of very acidic and/or basic proteins. The development of IPGs between pH 2.5-12 has enabled the analysis of very alkaline proteins and the construction of the corresponding databases. Narrow-overlapping IPGs provide increased resolution (delta pI = 0.001) and, in combination with prefractionation methods, the detection of low abundance proteins. Depending on the gel size and pH gradient used, 2-DE can resolve more than 5000 proteins simultaneously (approximately 2000 proteins routinely), and detect and quantify < 1 ng of protein per spot. In this article we describe the current 2-DE/MS workflow including the following topics: sample preparation, protein solubilization, and prefractionation; protein separation by 2-DE with IPGs; protein detection and quantitation; computer assisted analysis of 2-DE patterns; protein identification and characterization by MS; two-dimensional protein databases.

Current two‐dimensional electrophoresis technology for proteomics

https://www.spg.pt/wp-content/uploads/2015/11/2013-ACG_Guideline_AcutePancreatitis_September_2013.pdf

American College of Gastroenterology guideline: management of acute pancreatitis.

Background The results of case-control studies and anecdotal reports suggest that pancreatitis may be a risk factor for pancreatic cancer, but there have been no studies of sufficient size and power to assess the magnitude of the relation between these two diseases. Methods and Results We undertook a multicenter historical cohort study of 2015 subjects with chronic pancreatitis who were recruited from clinical centers in six countries. A total of 56 cancers were identified among these patients during a mean (±SD) follow-up of 7.4 ±6.2 years. The expected number of cases of cancer calculated from country-specific incidence data and adjusted for age and sex was 2.13, yielding a standardized incidence ratio (the ratio of observed to expected cases) of 26.3 (95 percent confidence interval, 19.9 to 34.2). For subjects with a minimum of two or five years of follow-up, the respective standardized incidence ratios were 16.5 (95 percent confidence interval, 11.1 to 23.7) and 14.4 (95 percent confidence interval, 8...

https://www.nejm.org/doi/pdf/10.1056/NEJM199305203282001

Pancreatitis and the risk of pancreatic cancer

Course and outcome of chronic pancreatitis. Longitudinal study of a mixed medical-surgical series of 245 patients.

https://www.gastrojournal.org/article/S0016-5085(99)70016-8/pdf

The natural history of pain in alcoholic chronic pancreatitis

Surveillance for alveolar echinococcosis in central Europe was initiated in 1998. On a voluntary basis, 559 patients were reported to the registry. Most cases originated from rural communities in regions from eastern France to western Austria; single cases were reported far away from the disease-"endemic" zone throughout central Europe. Of 210 patients, 61.4% were involved in vocational or part-time farming, gardening, forestry, or hunting. Patients were diagnosed at a mean age of 52.5 years; 78% had symptoms. Alveolar echinococcosis primarily manifested as a liver disease. Of the 559 patients, 190 (34%) were already affected by spread of the parasitic larval tissue. Of 408 (73%) patients alive in 2000, 4.9% were cured. The increasing prevalence of Echinococcus multilocularis in foxes in rural and urban areas of central Europe and the occurrence of cases outside the alveolar echinococcosis-endemic regions suggest that this disease deserves increased attention.

European echinococcosis registry: human alveolar echinococcosis, Europe, 1982-2000.

https://www.gastrojournal.org/article/S0016-5085(96)00321-6/pdf

Rudolf W. Ammann

Papers

Pancreatitis and the risk of pancreatic cancer

Course and outcome of chronic pancreatitis. Longitudinal study of a mixed medical-surgical series of 245 patients.

The natural history of pain in alcoholic chronic pancreatitis

European echinococcosis registry: human alveolar echinococcosis, Europe, 1982-2000.

Course of alcoholic chronic pancreatitis: a prospective clinicomorphological long-term study.