A randomized translational study on protein- and glucose metabolism in skeletal muscles evaluated by gene-ontology, following preoperative oral carbohydrate loading compared to overnight peripheral parenteral nutrition (PPN) before major cancer surgery.

Background: Effects of preoperative drinks on muscle metabolism are unclear despite general recommendations. The aim of the present study was therefore to compare metabolic effects of a preoperative oral nutrition drink, recommended by protocols for enhanced recovery after surgery (ERAS), compared to overnight preoperative peripheral total parenteral nutrition (PPN) on skeletal muscle metabolism in patients aimed at major gastrointestinal cancer surgery.

Methods: Patients were randomized, based on diagnosis and clinical characteristics, to receive either a commercial carbohydrate-rich nutrition drink (Drink); or overnight (12 h) peripheral parenteral nutrition (PPN) as study regimens; compared to isotone Ringer-acetate as Control regimen.

Long-Term Changes to the Microbiome, Blood Lipid Profiles and IL-6 in Female and Male Swedish Patients in Response to Bariatric Roux-en-Y Gastric Bypass.

Lipid metabolism dysregulation is a critical factor contributing to obesity. To counteract obesity-associated disorders, bariatric surgery is implemented as a very effective method. However, surgery such as Roux-en-Y gastric bypass (RYGB) is irreversible, resulting in life-long changes to the digestive tract.

Acute appendicitis: A block-randomized study on active observation with or without antibiotic treatment.

Background: Antibiotic treatment of unselected patients with acute appendicitis is safe and effective. However, it is unknown to what extent early provision of antibiotic treatment may represent overtreatment due to spontaneous healing of appendix inflammation. The aim of the present study was to evaluate the role of antibiotic treatment versus active in-hospital observation on spontaneous regression of acute appendicitis.

Parathyroid hormone related protein (PTHrP) in patients with pancreatic carcinoma and overt signs of disease progression and host tissue wasting.

Background: Cancer-cachexia is a complex syndrome secondary to physiological mechanisms related to classical hormone and immune alterations, where contributions of neuro-endocrine involvement have been less evaluated. Therefore, the aim of our study was to explore relationships between PTHrP and whole body metabolism in patients with progressive pancreatic carcinoma; relevant to "fat tissue browning".

Methods: Patient serum samples and clinical information were retrieved from earlier translational projects (1995-2005), at Sahlgrenska University Hospital in Gothenburg.

Initiation of muscle protein synthesis was unrelated to simultaneously upregulated local production of IGF-1 by amino acids in non-proliferating L6 muscle cells.

Background: IGF-1 is considered an important regulator of muscle protein synthesis. However, its role in stimulation of muscle protein synthesis by amino acids (AA) is not clear, despite pronounced alterations in IGF-1 mRNA expression and signaling in muscle tissues by feeding. This study evaluates the role of locally produced IGF-1 and IGF-1 signaling when skeletal muscle protein synthesis is activated by increased amino acid availability in confluent, non-proliferating cells.

Reduced tumor growth in EP2 knockout mice is related to signaling pathways favoring an increased local anti‑tumor immunity in the tumor stroma.

Inflammatory signaling through prostaglandin E2 receptor subtype 2 (EP2) is associated with malignant tumor growth in both experimental models and cancer patients. Thus, the absence of EP2 receptors in host tissues appears to reduce tumor growth and systemic inflammation by inducing major alterations in gene expression levels across tumor tissue compartments. However, it is not yet well‑established how signaling pathways in tumor tissue relate to simultaneous signaling alterations in the surrounding tumor‑stroma, at conditions of reduced disease progression due to decreased host inflammation.

LPS immune challenge reduces arcuate nucleus TSHR and CART mRNA and elevates plasma CART peptides.

Background: The aim was to examine the impact of lipopolysaccharide-induced systemic inflammation on expression of mRNA for cocaine- and amphetamine-regulated transcript (CART) and the thyrotropin receptor (TSHR) and its ligands in CNS areas of relevance for feeding controls and metabolism. Lipopolysaccharide effects on plasma levels of TSH and CART peptides were also examined.

Methods: Lipopolysaccharide (150-200 μg/mouse) was injected in C57BL/6J mice and tissue and plasma samples taken after 24 h.

Estrogen biosynthesis in cultured skeletal muscle cells (L6) induced by amino acids.

Background: Previous investigations have indicated upregulation of gene expression in cellular pathways related to the biosynthesis of steroids in response to amino acids (AA) in skeletal muscle cells. This suggests AA as modulators of de novo synthesis of sex steroids for muscle growth and improved functional capacity. The aim of the present study was to investigate if increased availability of amino acids induced biosynthesis of sex steroids in skeletal muscles.

EGFR, but not COX-2, protein in resected pancreatic ductal adenocarcinoma is associated with poor survival.

The effects of EGFR and COX-2 protein overexpression on clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) patients remains unclear. Therefore, the aim of the present study was to evaluate the protein expression of epithelial growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in tumor cells in surgically resected PDAC, in comparison with clinicopathological characteristics and clinical outcomes. Immunohistochemical staining of formalin-fixed paraffin-embedded tissue derived from surgically resected tumors was performed.

Determinants of change in resting energy expenditure in patients with stage III/IV colorectal cancer.

Background & Aims: Resting energy expenditure (REE) is variable in cancer and might be influenced by changes in tumor burden, systemic inflammation, and body composition. The objective of this study was to assess REE change and the predictors of such in patients with stage III or IV colorectal cancer.

Methods: REE was measured via indirect calorimetry and fat mass and fat-free mass (FFM) were assessed using dual X-ray absorptiometry as part of a unique analysis of two studies.

Fractional uptake of circulating tumor cells into liver-lung compartments during curative resection of periampullary cancer.

Circulating tumor cells (CTCs) are able to predict outcome in patients with breast, colon and prostate cancer and appear to be promising biomarkers of pancreatic carcinoma. The aim of the present study was to demonstrate a statistically significant portal-arterial difference of CTCs during curative resection of periampullary cancer. A commercially available instrument (Isoflux) was used to quantify blood content of CTC in 10 patients with periampullary cancer according to preoperative diagnostics.

Overnight Steady-State Infusions of Parenteral Nutrition on Myosin Heavy Chain Transcripts in Rectus Abdominis Muscle Related to Amino Acid Transporters, Insulin-like Growth Factor 1, and Blood Amino Acids in Patients Aimed at Major Surgery.

Background: Evaluation of improvements by nutrition support to severely ill patients requires sensitive methods to demonstrate activation of protein synthesis in various tissues from groups with a limited number of patients to be statistically efficient. This study examines effects of standard parenteral nutrition (PN) on abdominal muscle transcripts of amino acid (AA) transporters, myosin heavy chains (MHCs), and the insulin-like growth factor 1 and its receptor (IGF-1/IGF-1R) in patients aimed at major surgery.

Methods: Twenty-two randomized patients received steady-state PN (0.

Long-Term Results Following Antibiotic Treatment of Acute Appendicitis in Adults.

Background: Antibiotic treatment of acute appendicitis has gained interest and inquiries. Reports have demonstrated both safety and high resolution of symptoms and inflammation following antibiotic treatment of appendicitis, but information on long-term results is required. Our present aim was therefore to evaluate long-term recurrence rate of initial antibiotics-alone treatment for suspected acute appendicitis.

Host knockout of E-prostanoid 2 receptors reduces tumor growth and causes major alterations of gene expression in prostaglandin E-producing tumors.

Prostaglandin E (PGE) is elevated in a variety of malignant tumors and has been shown to affect several hallmarks of cancer. Accordingly, the PGE receptor, E-prostanoid 2 (EP2), has been reported to be associated with patient survival and reduced tumor growth in EP2-knockout mice. Thus, the aim of the present study was to screen for major gene expression alterations in tumor tissue growing in EP2-knockout mice.

Preoperative overnight parenteral nutrition (TPN) improves skeletal muscle protein metabolism indicated by microarray algorithm analyses in a randomized trial.

Loss of muscle mass is associated with increased risk of morbidity and mortality in hospitalized patients. Uncertainties of treatment efficiency by short-term artificial nutrition remain, specifically improvement of protein balance in skeletal muscles. In this study, algorithmic microarray analysis was applied to map cellular changes related to muscle protein metabolism in human skeletal muscle tissue during provision of overnight preoperative total parenteral nutrition (TPN).

Presence of TSH receptors in discrete areas of the hypothalamus and caudal brainstem with relevance for feeding controls-Support for functional significance.

Aims: Previous studies have shown that brain-derived thyroid-stimulating hormone (TSH) and its receptor (TSHr) are present in hypothalamic extracts. No studies investigating both the anatomical location and functional significance of putative TSHr proteins in specific central nervous system (CNS) nuclei involved in feeding controls have yet been conducted. The aim was thus to determine whether TSHr are present in nuclei associated with feeding behavior, and if such receptors may be functional.

MCG101-induced cancer anorexia-cachexia features altered expression of hypothalamic Nucb2 and Cartpt and increased plasma levels of cocaine- and amphetamine-regulated transcript peptides.

The aim of the present study was to explore central and peripheral host responses to an anorexia-cachexia producing tumor. We focused on neuroendocrine anorexigenic signals in the hypothalamus, brainstem, pituitary and from the tumor per se. Expression of mRNA for corticotropin-releasing hormone (CRH), cocaine- and amphetamine-regulated transcript (CART), nesfatin-1, thyrotropin (TSH) and the TSH receptor were explored.

Alterations in Tumor DNA Are Related to Short Postoperative Survival in Patients Resected for Pancreatic Carcinoma Aimed at Cure.

Objectives: Pancreatic ductal adenocarcinomas (PDACs) are found in more than 85% of patients with pancreatic cancer and with 5-year survival of less than 10%. Effective treatment may be radical surgery, which is hampered by rapid relapse. Therefore, our aim was to compare DNA sequence alterations in patients with short and long survival to evaluate if confirmed DNA alterations predict short postoperative survival.

Food intake, tumor growth, and weight loss in EP2 receptor subtype knockout mice bearing PGE2-producing tumors.

Previous studies in our laboratory have demonstrated that prostaglandin (PG) E2 is involved in anorexia/cachexia development in MCG 101 tumor-bearing mice. In the present study, we investigate the role of PGE receptor subtype EP2 in the development of anorexia after MCG 101 implantation in wild-type (EP2 (+/+)) or EP2-receptor knockout (EP2(-/-)) mice. Our results showed that host absence of EP2 receptors attenuated tumor growth and development of anorexia in tumor-bearing EP2 knockout mice compared to tumor-bearing wild-type animals.

Circulating carnosine dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer.

Background: Cancer cachexia (CC) is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia.

Loss of muscle mass in the end of life in patients with advanced cancer.

Purpose: Muscle mass depletion is associated with adverse outcomes in cancer patients. There is limited information on the impact of age, sex, tumor type, and inflammation on muscle loss in the end of life of cancer patients.

Methods: Muscle depletion and loss of muscle in the last 2 years of life was estimated in 471 cancer patients from 779 dual-energy X-ray absorptiometry scans.

Expression of major histocompatibility complex class I-related chain A/B (MICA/B) in pancreatic carcinoma.

Major histocompatibility complex class I-related chain A and B (MICA/B) are two stress-inducible ligands that bind to the immunoreceptor NKG2D and play an important role in mediating cytotoxicity of NK and T cells. Release of MIC molecules from the cell surface is thought to constitute an immune escape mechanism of tumor cells and thus could be associated with more aggressive course of tumor growth. In this study, we investigated the expression of MICA/B in ductal pancreatic carcinoma and serum in relation to tumor stage, differentiation and survival.

EGF receptor and COX-1/COX-2 enzyme proteins as related to corresponding mRNAs in human per-operative biopsies of colorectal cancer.

Background: Cyclooxygenase (COX) and epidermal growth factor receptor (EGFR) activities promote progression of colorectal cancer. Combined treatment against these targets has not been more effective than single treatments alone. Therefore, our aim was to analyze relationships between COX and EGFR in peroperative colorectal tumor biopsies.

Pituitary adenylate cyclase-activating polypeptide 6-38 blocks cocaine- and amphetamine-regulated transcript Peptide-induced hypophagia in rats.

Cocaine- and amphetamine-regulated transcript peptides (CARTp) suppress nutritional intake after administration into the fourth intracerebral ventricle. Recent in vitro studies have shown that PACAP 6-38, a pituitary adenylate cyclase-activating polypeptide (PACAP) fragment, could act as a competitive antagonist against CARTp 55-102 on a common CARTp-sensitive receptor structure. Here, we show for the first time in vivo that the reduction in solid food intake induced by exogenous CARTp 55-102 (0.

Liver-derived endocrine IGF-I is not critical for activation of skeletal muscle protein synthesis following oral feeding.

Background: Insulin-like growth factor-1 (IGF-1) is produced in various tissues to stimulate protein synthesis under different conditions. It is however, difficult to distinguish effects by locally produced IGF-1 compared to liver-derived IGF-1 appearing in the circulation. In the present study the role of liver-derived endocrine IGF-I for activation of skeletal muscle protein synthesis following feeding was evaluated.