Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma.

Background And Aims: Pancreatic cancer risk is increased in Lynch syndrome (LS) patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI). However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI in surgically resected pancreatic cancers in a multicentric, retrospective study, and to assess the occurrence of pancreatic cancer in LS.

LGR4 and LGR6 are differentially expressed and of putative tumor biological significance in gastric carcinoma.

Gastric cancer (GC) is one of the most common causes of cancer-related deaths worldwide. We investigated the differential expression and putative tumor biological significance of five G-protein-coupled receptors (GPCRs) in GC, i.e.

Endosonographic large-bore biopsy of gastric subepithelial tumors: a prospective multicenter study.

Background: Once gastric subepithelial lesions (SEL) are found, tissue diagnosis is required, considering the possible differential diagnosis of gastrointestinal stromal tumors (GIST). Previous studies have shown insufficient accuracy of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) using cytologic analysis.

Methods: The feasibility and yield of EUS-FNA-based histologic tissue acquisition for gastric SEL, using 19 G large-bore needles, was assessed in a 4-year multicenter, prospective study.

HPV status in patients with head and neck of carcinoma of unknown primary site: HPV, tobacco smoking, and outcome.

Objectives: Infection with human papillomavirus (HPV) is linked to oropharyngeal cancer. This analysis investigated possible associations between HPV status, smoking history and survival outcome in patients with neck metastasis and carcinoma of unknown primary (CUP).

Materials And Methods: Registries at the Universities of Hamburg and Kiel were searched for patients with CUP diagnosed from 2002 to 2011 who had formalin-fixed and paraffin-embedded metastatic lymph node samples available.

Hepatitis B virus-induced lipid alterations contribute to natural killer T cell-dependent protective immunity.

In most adult humans, hepatitis B is a self-limiting disease leading to life-long protective immunity, which is the consequence of a robust adaptive immune response occurring weeks after hepatitis B virus (HBV) infection. Notably, HBV-specific T cells can be detected shortly after infection, but the mechanisms underlying this early immune priming and its consequences for subsequent control of viral replication are poorly understood. Using primary human and mouse hepatocytes and mouse models of transgenic and adenoviral HBV expression, we show that HBV-expressing hepatocytes produce endoplasmic reticulum (ER)-associated endogenous antigenic lipids including lysophospholipids that are generated by HBV-induced secretory phospholipases and that lead to activation of natural killer T (NKT) cells.

Green tea halts progression of cardiac transthyretin amyloidosis: an observational report.

Background: Treatment options in patients with amyloidotic transthyretin (ATTR) cardiomyopathy are limited. Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea (GT), inhibits fibril formation from several amyloidogenic proteins in vitro. Thus, it might also halt progression of TTR amyloidosis.

The spatial distribution of LGR5+ cells correlates with gastric cancer progression.

In this study we tested the prevalence, histoanatomical distribution and tumour biological significance of the Wnt target protein and cancer stem cell marker LGR5 in tumours of the human gastrointestinal tract. Differential expression of LGR5 was studied on transcriptional (real-time polymerase chain reaction) and translational level (immunohistochemistry) in malignant and corresponding non-malignant tissues of 127 patients comprising six different primary tumour sites, i.e.

HPV DNA, E6*I-mRNA expression and p16INK4A immunohistochemistry in head and neck cancer - how valid is p16INK4A as surrogate marker?

It has been proposed that p16(INK4A) qualifies as a surrogate marker for viral oncogene activity in head and neck cancer (HNSCC). By analyzing 78 HNSCC we sought to validate the accuracy of p16(INK4A) as a reliable marker of active HPV infections in HNSCC. To this end we determined HPV DNA (HPVD) and E6*I mRNA (HPVR) expression status and correlated these results with p16(INK4A) staining.

Bile acids down-regulate caveolin-1 in esophageal epithelial cells through sterol responsive element-binding protein.

Bile acids are synthesized from cholesterol and are major risk factors for Barrett adenocarcinoma (BAC) of the esophagus. Caveolin-1 (Cav1), a scaffold protein of membrane caveolae, is transcriptionally regulated by cholesterol via sterol-responsive element-binding protein-1 (SREBP1). Cav1 protects squamous epithelia by controlling cell growth and stabilizing cell junctions and matrix adhesion.

Pan-histone deacetylase inhibitor panobinostat sensitizes gastric cancer cells to anthracyclines via induction of CITED2.

Background & Aims: Chemotherapy modestly prolongs survival of patients with advanced gastric cancer, but strategies are needed to increase its efficacy. Histone deacetylase (HDAC) inhibitors modify chromatin and can block cancer cell proliferation and promote apoptosis.

Methods: Gastric cancer cell lines were incubated with the HDAC inhibitor LBH589 (Panobinostat, Novartis, Germany); levels of proliferation, apoptosis, histone acetylation, and gene expression were determined.

Reassessment of sst3 somatostatin receptor expression in human normal and neoplastic tissues using the novel rabbit monoclonal antibody UMB-5.

Background: Among the five somatostatin receptors (sst(1)-sst(5)), the sst(3) receptor displays a distinct pharmacological profile. Like sst(2), the sst(3) receptor efficiently internalizes radiolabeled somatostatin analogs. Unlike sst(2), however, internalized sst(3) receptors are rapidly transferred to lysosomes for degradation.

TFAP2E-DKK4 and chemoresistance in colorectal cancer.

Background: Chemotherapy for advanced colorectal cancer leads to improved survival; however, predictors of response to systemic treatment are not available. Genomic and epigenetic alterations of the gene encoding transcription factor AP-2 epsilon (TFAP2E) are common in human cancers. The gene encoding dickkopf homolog 4 protein (DKK4) is a potential downstream target of TFAP2E and has been implicated in chemotherapy resistance.

Immunohistochemistry in the classification of systemic forms of amyloidosis: a systematic investigation of 117 patients.

Amyloidoses are characterized by organ deposition of misfolded proteins. This study evaluated immunohistochemistry as a diagnostic tool for the differentiation of amyloid subentities, which is warranted for accurate treatment. A total of 117 patients were systematically investigated by clinical examination, laboratory tests, genotyping, and immunohistochemistry on biopsy specimens.

Detection of KRAS and BRAF mutations in advanced colorectal cancer by allele-specific single-base primer extension.

Evaluation of: Magnin S, Viel E, Baraquin A et al. A multiplex SNaPshot assay as a rapid method for detecting KRAS and BRAF mutations in advanced colorectal cancers. J.

Skeletal scintigraphy indicates disease severity of cardiac involvement in patients with senile systemic amyloidosis.

Background: Senile systemic amyloidosis (SSA) is a common aging phenomenon in the elderly population. Nevertheless, pre-mortem diagnosis of SSA is rare. Thus, data on clinical characterization and disease severity are limited.

KRAS, NRAS, PIK3CA exon 20, and BRAF genotypes in synchronous and metachronous primary colorectal cancers diagnostic and therapeutic implications.

Targeted therapy of advanced colorectal carcinoma (CRC) necessitates KRAS genotyping. Because we were interested in diagnostic and therapeutic consequences, we studied the KRAS, NRAS, PIK3CA exon 20, and BRAF genotypes in synchronous and metachronous primary CRCs; in addition, we studied their available metastases. We studied 21 patients with 43 synchronous and 2 metachronous adenocarcinomas of the colorectum (n = 20) and stomach (n = 1).

The Ras inhibitors caveolin-1 and docking protein 1 activate peroxisome proliferator-activated receptor γ through spatial relocalization at helix 7 of its ligand-binding domain.

Peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that promotes differentiation and cell survival in the stomach. PPARγ upregulates and interacts with caveolin-1 (Cav1), a scaffold protein of Ras/mitogen-activated protein kinases (MAPKs). The cytoplasmic-to-nuclear localization of PPARγ is altered in gastric cancer (GC) patients, suggesting a so-far-unknown role for Cav1 in spatial regulation of PPARγ signaling.

Farnesoid X receptor protects human and murine gastric epithelial cells against inflammation-induced damage.

Bile acids from duodenogastric reflux promote inflammation and increase the risk for gastro-oesophageal cancers. FXR (farnesoid X receptor/NR1H4) is a transcription factor regulated by bile acids such as CDCA (chenodeoxycholic acid). FXR protects the liver and the intestinal tract against bile acid overload; however, a functional role for FXR in the stomach has not been described.

Cohort study based on the seventh edition of the TNM classification for gastric cancer: proposal of a new staging system.

Purpose: We investigated the effect of the new TNM classification on gastric cancer staging.

Patients And Methods: From hospital records, information from patients with gastric cancer, who had undergone either total or partial gastrectomy for adenocarcinomas of the stomach or esophagogastric junction, was retrieved. The pathologic TNM stage was determined according to the sixth and seventh editions of the International Union Against Cancer guidelines and was based on surgical pathologic examination.

The level of secretory leukocyte protease inhibitor is decreased in metastatic head and neck squamous cell carcinoma.

Head and neck squamous cell carcinomas (HNSCC) represent the sixth largest group among all human malignancies. However, the exact molecular mechanisms inducing the genesis and the progression of metastasis in these tumors are poorly understood. The identification of molecular alterations involved in metastasis of HNSCC might influence the value of clinical diagnostics, impact therapy strategies and finally improve the prognosis of the patients.

Distinct DNA methylation patterns in cirrhotic liver and hepatocellular carcinoma.

Abberrant DNA methylation is one of the hallmarks of cancerogenesis. Our study aims to delineate differential DNA methylation in cirrhosis and hepatic cancerogenesis. Patterns of methylation of 27,578 individual CpG loci in 12 hepatocellular carcinomas (HCCs), 15 cirrhotic controls and 12 normal liver samples were investigated using an array-based technology.

Genotypic and phenotypic characterization of side population of gastric cancer cell lines.

The side population (SP) of tumor cell lines shares characteristics with tumor stem cells. The objective of this study was to phenotypically and genotypically characterize the SP of gastric cancer cell lines. SP cells were obtained from AGS and MKN45 gastric cancer cells using Hoechst 33342 staining and fluorescence-activated cell sorting.

PTAA and B10: new approaches to amyloid detection in tissue-evaluation of amyloid detection in tissue with a conjugated polyelectrolyte and a fibril-specific antibody fragment.

Aims: We analysed the suitability of two little known substances for the detection of amyloid in surgical pathology specimens, that is the conjugated polyelectrolyte polythiophene acetic acid (PTAA) and the camelid antibody domain B10.

Methods: We compared the amyloid detection of PTAA and B10 to Congo red in 106 amyloid-containing tissue biopsies of diverse anatomical and precursor origin by evaluating the accordance in four grades (grade 0: no staining, grade 1: staining of <33% of the amyloid deposits, grade 2: 33-66% and grade 3:>66%).

Results: PTAA showed grade 2-3 staining in 57 (54%) cases, while B10 presented this accordance in only 25 (24%) tissue biopsies.

Pattern recognition with a fibril-specific antibody fragment reveals the surface variability of natural amyloid fibrils.

Amyloid immunotherapy has led to the rise of antibodies, which target amyloid fibrils or structural precursors of fibrils, based on their specific conformational properties. Recently, we reported the biotechnological generation of the B10 antibody fragment, which provides conformation-specific binding to amyloid fibrils. B10 strongly interacts with fibrils from Alzheimer's β amyloid (Aβ) peptide, while disaggregated Aβ peptide or Aβ oligomers are not explicitly recognized.