Sensitivity of Bragg gratings in birefringent optical fiber to transverse compression between conforming materials.

A theoretical and experimental investigation of the transverse load sensitivity of Bragg gratings in birefringent fibers to conforming contact is presented. A plane elasticity model is used to predict the contact dimensions between a conforming material and optical fiber and the principal stresses, indicating birefringence, created as a result of this contact. The transverse load sensitivity of commercially available birefringent fiber is experimentally measured for two cases of conforming contact.

Glucosylceramide synthesis inhibition affects cell cycle progression, membrane trafficking, and stage differentiation in Giardia lamblia.

Synthesis of glucosylceramide via glucosylceramide synthase (GCS) is a crucial event in higher eukaryotes, both for the production of complex glycosphingolipids and for regulating cellular levels of ceramide, a potent antiproliferative second messenger. In this study, we explored the dependence of the early branching eukaryote Giardia lamblia on GCS activity. Biochemical analyses revealed that the parasite has a GCS located in endoplasmic reticulum (ER) membranes that is active in proliferating and encysting trophozoites.

Serotonin promotes tumor growth in human hepatocellular cancer.

Unlabelled: In addition to its function as a neurotransmitter and vascular active molecule, serotonin is also a mitogen for hepatocytes and promotes liver regeneration. A possible role in hepatocellular cancer has not yet been investigated. Human hepatocellular cancer cell lines Huh7 and HepG2 were used to assess the function of serotonin in these cell lines.

Reduced expression of fibroblast growth factor receptor 2IIIb in hepatocellular carcinoma induces a more aggressive growth.

Fibroblast growth factor receptor 2 isoform b (FGFR2-IIIb) is highly expressed in hepatocytes and plays an important role in liver homeostasis and regeneration. Here, we analyzed the expression and function of FGFR2-IIIb in hepatocellular carcinoma (HCC). FGFR2-IIIb expression in HCC tissues and cell lines was lower than in primary human hepatocytes and nontumorous tissue.

Mining tissue microarray data to uncover combinations of biomarker expression patterns that improve intermediate staging and grading of clear cell renal cell cancer.

Purpose: Tumor stage and nuclear grade are the most important prognostic parameters of clear cell renal cell carcinoma (ccRCC). The progression risk of ccRCC remains difficult to predict particularly for tumors with organ-confined stage and intermediate differentiation grade. Elucidating molecular pathways deregulated in ccRCC may point to novel prognostic parameters that facilitate planning of therapeutic approaches.

Nuclear detection of Y-box protein-1 (YB-1) closely associates with progesterone receptor negativity and is a strong adverse survival factor in human breast cancer.

Background: Y-box binding protein-1 (YB-1) is the prototypic member of the cold shock protein family that fulfills numerous cellular functions. In the nucleus YB-1 protein orchestrates transcription of proliferation-related genes, whereas in the cytoplasm it associates with mRNA and directs translation. In human tumor entities, such as breast, lung and prostate cancer, cellular YB-1 expression indicates poor clinical outcome, suggesting that YB-1 is an attractive marker to predict patients' prognosis and, potentially, is suitable to individualize treatment protocols.

The application of artificial intelligence to microarray data: identification of a novel gene signature to identify bladder cancer progression.

Background: New methods for identifying bladder cancer (BCa) progression are required. Gene expression microarrays can reveal insights into disease biology and identify novel biomarkers. However, these experiments produce large datasets that are difficult to interpret.

AID protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma is associated with poor prognosis and complex genetic alterations.

The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood.

Cyclooxygenase 2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Are Stage-Dependent Prognostic Markers of Malignant Melanoma.

Using tissue microarrays (TMAs) we studied COX2/PPARG immunoreactivity in a broad spectrum of tumors focussing on clinicopathological correlations and the outcome of patients with malignant melanoma (MM). TMA-1 contained normal and tumor tissues (n = 3448) from 47 organs including skin neoplasms (n = 323); TMA-2 88 primary MM, 101 metastases, and 161 benign nevi. Based on a biomodulatory approach combining COX/PPAR-targeting with metronomic low-dose chemotherapy metastases of 36 patients participating in a randomized trial with metastatic (stage IV) melanoma were investigated using TMA-3.

Neogenesis and maturation of transient Golgi-like cisternae in a simple eukaryote.

The highly reduced protozoan parasite Giardia lamblia has minimal machinery for cellular processes such as protein trafficking. Giardia trophozoites maintain diverse and regulated secretory pathways but lack an identifiable Golgi complex. During differentiation to cysts, however, they produce specialized compartments termed encystation-specific vesicles (ESVs).

No mutations of FGFR3 in normal urothelium in the vicinity of urothelial carcinoma of the bladder harbouring activating FGFR3 mutations in patients with bladder cancer.

Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene causing constitutive oncogenic protein activation have been shown to be frequent in papillary noninvasive bladder tumours and are associated with a low risk of progression and a favourable outcome. FGFR3 alterations have also been found in benign urothelial papilloma and flat urothelial hyperplasia suggesting FGFR3 alterations as an early event in bladder tumorigenesis. To date there is no data available on FGFR3 mutations in normal urothelium from patients with bladder cancer.

Reassessing the current UICC/AJCC TNM staging for renal cell carcinoma.

Context: The outcome prediction for renal cell cancer (RCC) remains controversial, and although many parameters have been tested for prognostic significance, only a few have achieved widespread acceptance in clinical practice. The TNM staging system defines local extension of the primary tumour (T), involvement of regional lymph nodes (N), and presence of distant metastases (M).

Objective: This review focuses on reassessing the current TNM staging system for RCC.

Prognostic relevance of Wnt-inhibitory factor-1 (WIF1) and Dickkopf-3 (DKK3) promoter methylation in human breast cancer.

Background: Secreted Wnt signaling antagonists have recently been described as frequent targets of epigenetic inactivation in human tumor entities. Since gene silencing of certain Wnt antagonists was found to be correlated with adverse patient survival in cancer, we aimed at investigating a potential prognostic impact of the two Wnt antagonizing molecules WIF1 and DKK3 in breast cancer, which are frequently silenced by promoter methylation in this disease.

Methods: WIF1 and DKK3 promoter methylation were assessed by methylation-specific PCR with bisulfite-converted DNA from 19 normal breast tissues and 150 primary breast carcinomas.

Detection of urothelial bladder cancer cells in voided urine can be improved by a combination of cytology and standardized microsatellite analysis.

Purpose: To evaluate molecular and immunohistochemical markers to develop a molecular grading of urothelial bladder cancer and to test these markers in voided urine samples.

Experimental Design: 255 consecutive biopsies from primary bladder cancer patients were evaluated on a tissue microarray. The clinical parameters gender, age, adjacent carcinoma in situ, and multifocality were collected.

Loss of VHL and hypoxia provokes PAX2 up-regulation in clear cell renal cell carcinoma.

Purpose: The paired box gene 2, PAX2, encodes for a transcription factor that is up-regulated during nephrogenesis and becomes silenced in mature epithelium of the glomeruli, the proximal, and distal tubules. Reactivation of PAX2 has been frequently observed in clear cell renal cell carcinoma (ccRCC), a tumor type characterized by loss of von Hippel-Lindau (VHL) tumor suppressor function. The regulation of PAX2 expression in ccRCC is unknown.

Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas.

Unlabelled: Hepatocellular carcinomas (HCCs) and bile duct carcinomas (BDCs) have a poor prognosis. Therefore, surveillance strategies including sensitive and specific serum markers for early detection are needed. Recently, Golgi Phosphoprotein 2 (GOLPH2) has been proposed as a serum marker for HCC, but GOLPH2 expression data in liver tissues was not available.

Genetic and epigenetic SLC18A2 silencing in prostate cancer is an independent adverse predictor of biochemical recurrence after radical prostatectomy.

Purpose: This study investigates SLC18A2 (vesicular monoamine transporter 2) expression in prostate adenocarcinoma and examines its potential as a predictive marker for prostate cancer patient outcome after radical prostatectomy.

Experimental Design: Expression and single nucleotide polymorphism microarray analyses identified SLC18A2 as both down-regulated and subject to common loss-of-heterozygosity in prostate cancer. Down-regulated SLC18A2 expression was validated on tissue microarrays containing benign and malignant prostate specimens from an independent patient group (n=738).

Down-regulation of CYLD expression by Snail promotes tumor progression in malignant melanoma.

High malignancy and early metastasis are hallmarks of melanoma. Here, we report that the transcription factor Snail1 inhibits expression of the tumor suppressor CYLD in melanoma. As a direct consequence of CYLD repression, the protooncogene BCL-3 translocates into the nucleus and activates Cyclin D1 and N-cadherin promoters, resulting in proliferation and invasion of melanoma cells.

Computational pathology analysis of tissue microarrays predicts survival of renal clear cell carcinoma patients.

Renal cell carcinoma (RCC) can be diagnosed by histological tissue analysis where exact counts of cancerous cell nuclei are required. We propose a completely automated image analysis pipeline to predict the survival of RCC patients based on the analysis of immunohistochemical staining of MIB-1 on tissue microarrays. A random forest classifier detects cell nuclei of cancerous cells and predicts their staining.

Expression of the endothelin axis in noninvasive and superficially invasive bladder cancer: relation to clinicopathologic and molecular prognostic parameters.

Background: The endothelin (ET) axis plays a role in cancer biology and plays a potential role as a target for molecular therapy in urogenital tumours. Alterations of several proteins of the ET axis were detected in invasive bladder cancer.

Objectives: To examine the potential role of the expression of ET axis proteins compared to other prognostic parameters (kinase inhibitor 67 [Ki-67], tumour protein 53 [TP53], and fibroblast growth factor receptor 3 gene [FGFR3] mutations) in noninvasive and invasive bladder cancer.

Frequent expression of the novel cancer testis antigen MAGE-C2/CT-10 in hepatocellular carcinoma.

Cancer testis (CT) antigens are attractive targets for immunotherapy in cancer patients. Immunohistochemistry was used to study the expression of the CT antigens MAGE-C2/CT-10, MAGE-C1/CT-7, GAGE, MAGE-A4 and NY-ESO-1 in 146 hepatocellular carcinomas, 13 intrahepatic cholangiocarcinomas, 37 extrahepatic cholangiocarcinomas and 32 gallbladder carcinomas. Immunopositivity was correlated with clinicopathological parameters, MHC Class 1 expression, intratumoral CD4+, CD8+ and FOXP3+ T cells and CD163+ antigen-presenting cells.

Exploring the nuclear envelope of herpes simplex virus 1-infected cells by high-resolution microscopy.

Herpesviruses are composed of capsid, tegument, and envelope. Capsids assemble in the nucleus and exit the nucleus by budding at the inner nuclear membrane, acquiring tegument and the envelope. This study focuses on the changes of the nuclear envelope during herpes simplex virus 1 (HSV-1) infection in HeLa and Vero cells by employing preparation techniques at ambient and low temperatures for high-resolution scanning and transmission electron microscopy and confocal laser scanning microscopy.

HER3 is a determinant for poor prognosis in melanoma.

Purpose: The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated with poor prognosis in breast, lung, and ovarian cancer. However, the relevance of HER3 with regard to its prognostic significance and function in primary melanoma and metastases remains largely elusive.

Experimental Design: HER3 protein expression was analyzed immunohistochemically using tissue microarrays of 130 primary melanoma and 87 metastases relative to established clinical variables.

Validation of a novel minimally invasive intervertebral disc pressure sensor utilizing in-fiber Bragg gratings in a porcine model: an ex vivo study.

Study Design: Nucleus pressure was measured within porcine intervertebral discs (IVDs) with a novel in-fiber Bragg grating (FBG) sensor (0.4 mm diameter) and a strain gauge (SG) sensor (2.45 mm).

Microarray comparative genomic hybridization analysis of tubular breast carcinoma shows recurrent loss of the CDH13 locus on 16q.

Tubular breast carcinoma is a highly differentiated carcinoma with an excellent prognosis. Distinct genetic alterations in tubular breast carcinoma cells have been described, especially broad genetic losses on the q-arm of chromosome 16. These are more common in lobular breast carcinoma and low-grade ductal carcinoma in situ than in ductal breast carcinoma and high-grade ductal carcinoma in situ.