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Several potential urinary biomarkers exhibiting an association with upper gastrointestinal tumour growth have been previously identified, of which S100A6, S100A9, rabenosyn-5 and programmed cell death 6-interacting protein (PDCD6IP) were further validated and found to be upregulated in malignant tumours. The cancer cohort from our previous study was subclassified to assess whether distinct molecular markers can be identified for each individual cancer type using a similar approach. Urine samples from patients with cancers of the stomach, oesophagus, oesophagogastric junction or pancreas were analysed by surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry using both CM10 and IMAC30 (Cu2+-complexed) chip types and LC-MS/MS-based mass spectrometry after chromatographic enrichment. This was followed by protein identification, pattern matching and validation by western blotting. We found 8 m/z peaks with statistical significance for the four cancer types investigated, of which m/z 2447 and 2577 were identified by pattern matching as fragments of cathepsin-B (CTSB) and cystatin-B (CSTB); both molecules are indicative of pancreatic cancer. Additionally, we observed a potential association of upregulated α-1-antichymotrypsin with pancreatic and gastric cancers, of PDCD6IP, vitelline membrane outer layer protein 1 homolog (VMO1) and triosephosphate isomerase (TPI1) with oesophagogastric junctional cancers, and of complement C4-A, prostatic acid phosphatase, azurocidin and histone-H1 with oesophageal cancer. Furthermore, the potential pancreatic cancer biomarkers CSTB and CTSB were validated independently by western blotting. Therefore, the present study identified two new potential urinary biomarkers that appear to be associated with pancreatic cancer. This may provide a simple, non-invasive screening test for use in the clinical setting. [ABSTRACT FROM AUTHOR]

Liver export protein synthetic rates are increased by oral meal feeding in weight-losing cancer patients. Am J Physiol Endocrinol Metab 279: E707-E714, 2000.--We have demonstrated previously that, in the fasting state, whereas albumin synthesis is similar in cachectic cancer patients compared with controls, fibrinogen synthesis is increased. Whether synthesis of these proteins is altered after an oral meal was examined in eight weight-losing pancreatic cancer patients and six healthy controls by use of an intravenous flooding dose of [[sup.2][H.sub.5]]- or [[.sup.2][H.sub.8]]phenylalanine. Cancer patients had a median weight loss of 19%, a significantly lower serum albumin concentration, and a significantly higher plasma fibrinogen concentration than controls (P [is less than] 0.005). Fasting albumin synthesis rates were similar between cancer patients and controls (median total synthesis rate 11.3 vs. 13.9 g/day, respectively) and rose on feeding by a similar degree (median 29 and 24%). The fasting fibrinogen total synthetic rate was significantly higher in cancer patients than in controls (median 3.3 vs. 1.0 g/day, P = 0.0019). In cancer patients in the fed state, fibrinogen synthetic rate rose, by a median of 38% (P = 0.012), whereas in controls there was no significant change. These findings demonstrate significant upregulation by feeding of acute-phase protein synthesis in cachectic cancer patients. albumin; fibrinogen; acute-phase protein response; pancreatic cancer

Abstract: Background: Sarcopenia is defined as the age‐related loss of skeletal muscle mass and function. While all humans lose muscle with age, 2–5% of elderly adults develop functional consequences (disabilities). The aim of this study was to investigate muscle myogenesis in healthy elderly adults, with or without sarcopenia, compared with middle‐aged controls using both in vivo and in vitro approaches to explore potential biomarker or causative molecular pathways associated with sarcopenic versus non‐sarcopenic skeletal muscle phenotypes during ageing. Methods: Biomarkers of multiple molecular pathways associated with muscle regeneration were analysed using quantitative polymerase chain reaction in quadriceps muscle samples obtained from healthy elderly sarcopenic (HSE, n = 7) or non‐sarcopenic (HENS, n = 21) and healthy middle‐aged control (HMC, n = 22) groups. An in vitro system of myogenesis (using myoblasts from human donors aged 17–83 years) was used to mimic the environmental challenges of muscle regeneration over time. Results: The muscle biopsies showed evidence of satellite cell activation in HENS (Pax3, P < 0.01, Pax7, P < 0.0001) compared with HMC. Early myogenesis markers Myogenic Differentiation 1 (MyoD1) and Myogenic factor 5 (Myf5) (P < 0.0001) and the late myogenesis marker myogenin (MyoG) (P < 0.01) were increased in HENS. In addition, there was a 30‐fold upregulation of TNF‐α in HENS compared with HMC (P < 0.0001). The in vitro system demonstrated age‐related upregulation of pro‐inflammatory cytokines (2‐fold upregulation of interleukin (IL)‐6, IL‐8 mRNA, increased secretion of tumor necrosis factor‐α (TNF‐α) and IL‐6, all P < 0.05) associated with impaired kinetics of myotube differentiation. The HSE biopsy samples showed satellite cell activation (Pax7, P < 0.05) compared with HMC. However, no significant upregulation of the early myogenesis (MyoD and Myf5) markers was evident; only the late myogenesis marker myogenin was upregulated (P < 0.05). Higher activation of the oxidative stress pathway was found in HENS compared with the HSE group. In contrast, there was 10‐fold higher upregulation of HSPA1A a stress‐induced chaperone acting upon misfolded proteins in HSE compared with the HENS group. Conclusions: Both pathological and adaptive processes are active in skeletal muscle during healthy ageing. Muscle regeneration pathways are activated during healthy ageing, but there is evidence of dysregulation in sarcopenia. In addition, increased cellular stress, with an impaired oxidative‐stress and mis‐folded protein response (HSPA1A), may be associated with the development of sarcopenia. The in vitro system of young and old myoblasts replicated some of the differences between young and old muscle. [ABSTRACT FROM AUTHOR]