Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma.

Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce the salt-retaining steroid hormone aldosterone and cause millions of cases of severe hypertension worldwide. Either of 2 somatic mutations in the potassium channel KCNJ5 (G151R and L168R, hereafter referred to as KCNJ5MUT) in adrenocortical cells account for half of APAs worldwide. These mutations alter channel selectivity to allow abnormal Na+ conductance, resulting in membrane depolarization, calcium influx, aldosterone production, and cell proliferation.

Preclinical assesement of survivin and XIAP as prognostic biomarkers and therapeutic targets in gastroenteropancreatic neuroendocrine neoplasia.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) represent a rare and heterogenous tumor entity. Importantly, the highly proliferative subgroup of neuroendocrine carcinoma (GEP-NEC) is characterized by high resistance to conventional chemotherapy. Consequently, there is an urgent need to identify novel therapeutic targets, especially for GEP-NEC.

Efficacy of Monsel Solution After Cervical Biopsy: A Randomized Trial.

Objectives: To estimate the efficacy and side effects of Monsel solution for hemostasis after cervical punch biopsy.

Methods: In a prospective, randomized trial, we compared application of Monsel solution versus a "wait and see" approach in women undergoing cervical punch biopsies in a 1:1 ratio. The primary end point was vaginal bleeding (VB) after 15 minutes measured by scoring a sanitary pad with a 5-level pictogram.

A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas.

International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following: (1) To improve concordance and to align with practical consequences, a 2-tiered system (low vs. high grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low grade.

Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma.

Approximately 50-70 % of patients with retroperitoneal or intraabdominal sarcoma develop a relapse after surgical therapy, including peritoneal sarcomatosis, an extremely rare site of metastatic disease which is associated with an extremely poor prognosis. Accordingly, the establishment of a permanent cell line derived from peritoneal sarcomatosis might provide a helpful tool to understand the biological behavior and to develop new therapeutic strategies. Thus, we established and characterized a liposarcoma cell line (Lipo-DUE1) from a peritoneal sarcomatosis that was permanently cultured without showing any morphological changes.

CXCR4--A Prognostic and Clinicopathological Biomarker for Pancreatic Ductal Adenocarcinoma: A Meta-Analysis.

Adenocarcinomas of the pancreatic duct (PDAC) are characteristically aggressive tumors that are extremely challenging to treat as curative surgical resection, the definitive treatment, is seldom possible. Regretably, most patients are diagnosed with metastatic disease at the time of initial presentation. In addition, current chemotherapeutic concepts that are used for advanced disease stages show frustrating results.

Analysis of Copy-Number Alterations in Single Cells Using Microarray-Based Comparative Genomic Hybridization (aCGH).

In this unit, we describe a workflow that enables array comparative genomic hybridization (aCGH) of single cells. The unit first describes the isolation and preparation of single peripheral mononuclear cells from blood (PBMC) to prepare a suitable reference DNA for aCGH experiments. An alternative procedure is described for the preparation of single cells of GM14667 and GM05423 cell lines to use as reference DNA and for sex-mismatched control experiments.

Integrin expression in esophageal squamous cell carcinoma: loss of the physiological integrin expression pattern correlates with disease progression.

The integrins are a family of heterodimeric transmembrane signaling receptors that mediate the adhesive properties of epithelial cells affecting cell growth and differentiation. In many epithelial malignancies, altered integrin expression is associated with tumor progression and often correlates with unfavorable prognosis. However, only few studies have investigated the role of integrin expression in esophageal squamous cell carcinoma (ESCC).

Surgical strategies in the therapy of non-small cell lung cancer.

Lung cancer represents the leading cause of cancer mortality worldwide. Despite improvements in preoperative staging, surgical techniques, neoadjuvant/adjuvant options and postoperative care, there are still major difficulties in significantly improving survival, especially in locally advanced non-small cell lung cancer (NSCLC). To date, surgical resection is the primary mode of treatment for stage I and II NSCLC and has become an important component of the multimodality therapy of even more advanced disease with a curative intention.

Small bowel volvulus as a complication of von Recklinghausen's disease: a case report.

We report the case of a 25-year-old male with Neurofibromatosis type I (NF-1), who presented at the time of admission with clinical findings of an acute abdomen caused by a mechanical obstruction. Computerized tomography showed a volvulus of the terminal ileum with mesenteric swirling as the cause of the patient's symptoms. Consecutive exploratory laparotomy confirmed the diagnosis and 70 cm of the small intestine was resected due to an affection of the mesentery by multiple neurofibromas.

New model for gastroenteropancreatic large-cell neuroendocrine carcinoma: establishment of two clinically relevant cell lines.

Recently, a novel WHO-classification has been introduced that divided gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) according to their proliferation index into G1- or G2-neuroendocrine tumors (NET) and poorly differentiated small-cell or large-cell G3-neuroendocrine carcinomas (NEC). Our knowledge on primary NECs of the GEP-system is limited due to the rarity of these tumors and chemotherapeutic concepts of highly aggressive NEC do not provide convincing results. The aim of this study was to establish a reliable cell line model for NEC that could be helpful in identifying novel druggable molecular targets.

Predictors of mortality for necrotizing soft-tissue infections: a retrospective analysis of 64 cases.

Purpose: Necrotizing soft-tissue infection (NSTI) is a rare, but rapidly progressive and life-threatening disease with a high morbidity and mortality. The aim of the present study was to evaluate predictors of mortality in a group of patients with NSTIs treated at a single center.

Methods: The medical records of all patients that were treated because of a NSTI at our department between 1996 and 2011 were retrospectively analyzed.

Encapsulation status of papillary thyroid microcarcinomas is associated with the risk of lymph node metastases and tumor multifocality.

The management of papillary microcarcinoma (PMC) of the thyroid is controversial, especially after partial thyroid resection for benign thyroid disease. In order to detect prognostic factors for PMC, we analyzed 116 patients with PMC for encapsulation status and lymph node metastases. Between 10/1992 and 12/2010, 116 patients with PMC have been operated in our department (87 females, 29 males, median age 49 years).

Role of survivin as prognostic and clinicopathological marker in gastric cancer: a meta-analysis.

Survivin has been implicated as a potential prognostic marker in a wide range of malignant tumours. However, the prognostic impact of survivin in gastric cancer remains to be controversial and published data are sometimes heterogeneous. Thus, aim of this study was to review the literature by performing an electronical database search via PubMed and EMBASE to identify eligible studies that assessed the impact of survivin as prognostic marker and its association with clinicopathological variables.

Expression of TRAIL-splice variants in gastric carcinomas: identification of TRAIL-γ as a prognostic marker.

Background: TNF-related apoptosis inducing ligand (TRAIL) belongs to the TNF-superfamily that induces apoptotic cell death in a wide range of neoplastic cells in vivo as well as in vitro. We identified two alternative TRAIL-splice variants, i.e.

Intrahepatic endometriosis as differential diagnosis: case report and literature review.

Intrahepatic endometriosis is one of the rarest forms of atypical endometriosis; only eighteen cases have been reported in the English literature. We describe the case of a 32-year-old woman, who presented with persistent, non-cyclical upper right quadrant abdominal pain, a central liver cyst, and no history of endometriosis. Three years previous, she was diagnosed with an intrahepatic cyst.

High EpCAM expression is linked to proliferation and lauren classification in gastric cancer.

Background: The association of EpCAM expression with the progression of gastric cancer remains unclear. Here, we investigated the expression of EpCAM in gastric cancer subtypes and correlated the data to tumor cell proliferation and clinicopathologic factors.

Methods: The intratumoral expression of EpCAM was assessed in 163 primary gastric cancers (61 diffuse-, 62 intestinal-, 32 mixed-type and 8 unclassified tumors) by immunohistochemistry, using the monoclonal antibody Ber-EP4.

A robust method to analyze copy number alterations of less than 100 kb in single cells using oligonucleotide array CGH.

Comprehensive genome wide analyses of single cells became increasingly important in cancer research, but remain to be a technically challenging task. Here, we provide a protocol for array comparative genomic hybridization (aCGH) of single cells. The protocol is based on an established adapter-linker PCR (WGAM) and allowed us to detect copy number alterations as small as 56 kb in single cells.

Prognostic and clinicopathological significance of survivin in colorectal cancer: a meta-analysis.

Survivin/BIRC5 is a potentially interesting prognostic marker and therapeutic target in colorectal cancer (CRC). However, the available data on survivin expression in CRC are heterogeneous. Thus, to clarify the prognostic relevance of survivin in patients with CRC and its association with clinicopathological parameters we performed a meta-analysis.

Impact of the 3D microenvironment on phenotype, gene expression, and EGFR inhibition of colorectal cancer cell lines.

Three-dimensional (3D) tumor cell cultures grown in laminin-rich-extracellular matrix (lrECM) are considered to reflect human tumors more realistic as compared to cells grown as monolayer on plastic. Here, we systematically investigated the impact of ECM on phenotype, gene expression, EGFR signaling pathway, and on EGFR inhibition in commonly used colorectal cancer (CRC) cell lines. LrECM on-top (3D) culture assays were performed with the CRC cell lines SW-480, HT-29, DLD-1, LOVO, CACO-2, COLO-205 and COLO-206F.

Snail1 expression in colorectal cancer and its correlation with clinical and pathological parameters.

Background: Snail1 is a transcription regulator of E-cadherin. The loss of E-cadherin seems to be a crucial step in the process of Epithelial-mesenchymal transition (EMT). EMT initiates invasion and proliferation in many tumours.

Infusion of CD133+ bone marrow-derived stem cells after selective portal vein embolization enhances functional hepatic reserves after extended right hepatectomy: a retrospective single-center study.

Objective: This study was designed to evaluate the clinical outcome of patients undergoing portal vein embolization (PVE) and autologous CD133 bone marrow-derived stem cell (CD133+ BMSC) application before extended right hepatectomy.

Background: We have previously shown that portal venous infusion of CD133+ BMSCs substantially increases hepatic proliferation, when compared with PVE alone.

Methods: : Among 40 consecutive patients with a median follow-up of 28 months (7.

Missense variants in hMLH1 identified in patients from the German HNPCC consortium and functional studies.

Missense mutations of the DNA mismatch repair gene MLH1 are found in a significant fraction of patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC) and their pathogenicity often remains unclear. We report here all 88 MLH1 missense variants identified in families from the German HNPCC consortium with clinical details of these patients/families. We investigated 23 MLH1 missense variants by two functional in vivo assays in yeast; seven map to the ATPase and 16 to the protein interaction domain.

Genetic disparity between primary tumours, disseminated tumour cells, and manifest metastasis.

Recent genetic analyses of paired samples from primary tumours and disseminated tumour cells have uncovered a bewildering genetic disparity. It was therefore proposed that ectopically residing tumour cells disseminate early and develop independently into metastases parallel to the primary tumour. Alternatively, these cells may represent an irrelevant cell population unable to spawn metastases whereas only cells that disseminated late in primary tumour development (which therefore are similar to the primary tumour) will form manifest metastasis.