Membranous expression of Her3 is associated with a decreased survival in head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) still remains a lethal malignancy benefiting from the identification of the new target for early detection and/or development of new therapeutic regimens based on a better understanding of the biological mechanism for treatment. The overexpression of Her2 and Her3 receptors have been identified in various solid tumors, but its prognostic relevance in HNSCC remains controversial.

Methods: Three hundred eighty-seven primary HNSCCs, 20 matching metasis and 17 recurrent HNSCCs were arrayed into tissue microarrays.

Uterine gland formation in mice is a continuous process, requiring the ovary after puberty, but not after parturition.

Uterine gland formation occurs postnatally in an ovary- and steroid-independent manner in many species, including humans. Uterine glands secrete substances that are essential for embryo survival. Disruption of gland development during the postnatal period prevents gland formation, resulting in infertility.

Downregulation of Filamin A interacting protein 1-like is associated with promoter methylation and induces an invasive phenotype in ovarian cancer.

Ovarian cancer is the most lethal gynecologic malignancy with a five-year survival rate below 25% for patients with stages III and IV disease. Identifying key mediators of ovarian cancer invasion and metastasis is critical to the development of more effective therapeutic interventions. We previously identified Filamin A interacting protein 1-like (FILIP1L) as an important mediator of cell proliferation and migration.

Paracrine SLPI secretion upregulates MMP-9 transcription and secretion in ovarian cancer cells.

Objectives: Secretory leukocyte protease inhibitor (SLPI) is amplified in serous ovarian cancer. We have dissected its function, showing it is a survival factor for ovarian cancer and promotes tumorigenesis and paclitaxel-resistance. We hypothesized that the protease inhibitory function was responsible for modulating SLPI's invasive capacity.

5α-Estrane-3β,17β-diol and 5β-estrane-3α,17β-diol: definitive screening biomarkers to sign nandrolone abuse in cattle?

17β-Nandrolone (17β-NT) is one of the most frequently misused anabolic steroids in meat producing animals. As a result of its extensive metabolism combined with the possibility of interferences with other endogenous compounds, detection of its illegal use often turns out to be a difficult issue. In recent years, proving the illegal administration of 17β-NT became even more challenging since the presence of endogenous presence of 17β-NT or some of its metabolite in different species was demonstrated.

European School of Internal Medicine (ESIM) in Brighton: experiences and reflections.

The European School of Internal Medicine (ESIM) is a meeting aimed at young physicians training in internal medicine throughout Europe. Since 1998 the school has been held annually, and in this report we reflect on our experiences during the recent school in Brighton in July 2010. The school combined a broad mix of lectures, workshops and case presentations covering a variety of rare diseases, and both faculty and residents participated with noticeable enthusiasm, making this a special experience for all of us.

A prospective audit of referral patterns to a dedicated Foot and Ankle surgical service.

Introduction: In order to ensure we provided an appropriate patient focused service we undertook a prospective audit of referrals to our surgical foot and ankle department in a large District General Hospital/Treatment centre.

Methodology: An audit was conducted over a 12 month period to establish the initial referral patterns to a dedicated foot and ankle service. This was undertaken by completion of a dedicated audit form, with departmentally agreed terms and domains following the International coding of diseases (ICD) system.

Fascin and CK4 as biomarkers for esophageal squamous cell carcinoma.

Background: Several studies have suggested that fascin, cytokeratin 14 and cytokeratin 4 may have significant roles as biomarkers for the progression and survival of esophageal squamous cell carcinoma (ESCC).

Materials And Methods: This study performed immunohistochemistry in tissue microarrays, profiling premalignant lesions and invasive tumors.

Results: Fascin increased across the following states as follows: normal-appearing epithelium (26%) to dysplasia (46%) to ESCC (68%), while CK4 was undetectable in ESCC (0%) compared to normal-appearing epithelium (45%) or dysplasia (41%).

Phase IIA trial testing erlotinib as an intervention against intraductal pancreatic mucinous neoplasms.

Intraductal papillary mucinous neoplasms (IPMN) are a distinct type of precursor lesions that cause about 5% of pancreatic adenocarcinoma (1, 2). Four-year survival rates of 40% to 75% are reported (3-7). There is currently no chemotherapy specifically approved for treating IPMNs.

Methylation profiling of mediastinal gray zone lymphoma reveals a distinctive signature with elements shared by classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma.

Background: Mediastinal gray zone lymphoma is a newly recognized entity with transitional morphological and immunophenotypic features between the nodular sclerosis subtype of Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma. Diagnostic criteria for mediastinal gray zone lymphoma are still challenging, and the optimal therapy is as yet undetermined. Epigenetic changes have been implicated in the loss of the B-cell program in classical Hodgkin's lymphoma, and might provide a basis for the immunophenotypic alterations seen in mediastinal gray zone lymphoma.

A multifunctional element in the mouse Igκ locus that specifies repertoire and Ig loci subnuclear location.

Nonbiased V gene usage for V(D)J joining is essential for providing an optimal immune system, but no cis-acting sequence with this function has been uncovered. We previously identified a recombination silencer and heterochromatin targeting element in the Vκ-Jκ intervening sequence of germline Igκ transgenes, which we termed Sis. We now have generated Sis knockout mice in the endogenous locus.

RUNX transcription factor-mediated association of Cd4 and Cd8 enables coordinate gene regulation.

T cell fate is associated with mutually exclusive expression of CD4 or CD8 in helper and cytotoxic T cells, respectively. How expression of one locus is temporally coordinated with repression of the other has been a long-standing enigma, though we know RUNX transcription factors activate the Cd8 locus, silence the Cd4 locus, and repress the Zbtb7b locus (encoding the transcription factor ThPOK), which is required for CD4 expression. Here we found that nuclear organization was altered by interplay among members of this transcription factor circuitry: RUNX binding mediated association of Cd4 and Cd8 whereas ThPOK binding kept the loci apart.

Factors influencing the degradation of archival formalin-fixed paraffin-embedded tissue sections.

The loss of antigenicity in archival formalin-fixed paraffin-embedded (FFPE) tissue sections negatively affects both diagnostic histopathology and advanced molecular studies. The mechanisms underlying antigenicity loss in FFPE tissues remain unclear. The authors hypothesize that water is a crucial contributor to protein degradation and decrement of immunoreactivity in FFPE tissues.

Global gene expression profiling and validation in esophageal squamous cell carcinoma and its association with clinical phenotypes.

Purpose: Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with poor prognosis. Understanding molecular changes in ESCC will enable identification of molecular subtypes and provide potential targets for early detection and therapy.

Experimental Design: We followed up a previous array study with additional discovery and confirmatory studies in new ESCC cases by using alternative methods.

Surgical management of pes cavus deformity with an underlying neurological disorder: a case presentation.

Charcot-Marie-Tooth disease is a complex group of motor and sensory disorders presenting with varying levels of deformity dependent on the chronology and specific subgroup of the disease. In this report, we discuss a 19-year-old man with Charcot-Marie-Tooth 1A, a progressive and aggressive form of hereditary sensorimotor neuropathy, with rigid forefoot and rearfoot deformity. The authors discuss the etiology, tests, and sequential surgical management of this condition, focusing on a triple arthrodesis including a closingwedge subtalar joint fusion and a dorsal closing wedge osteotomy of the first metatarsal.

Cell biology. A hand to support the implantation window.

A signaling pathway connects ovarian hormones to preparation of the mammalian uterus for pregnancy.

It takes two: communication between homologous alleles preserves genomic stability during V(D)J recombination.

Chromosome pairing is involved in X chromosome inactivation, a classic instance of monoallelic gene expression. Antigen receptor genes are also monoallelically expressed ("allelically excluded") by B and T lymphocytes, and we asked whether pairing contributed to the regulation of V(D)J recombination at these loci. We found that homologous immunoglobulin (Ig) alleles pair up during recombination.

Multimodal microscopy for automated histologic analysis of prostate cancer.

Background: Prostate cancer is the single most prevalent cancer in US men whose gold standard of diagnosis is histologic assessment of biopsies. Manual assessment of stained tissue of all biopsies limits speed and accuracy in clinical practice and research of prostate cancer diagnosis. We sought to develop a fully-automated multimodal microscopy method to distinguish cancerous from non-cancerous tissue samples.

An N-terminal truncated carboxypeptidase E splice isoform induces tumor growth and is a biomarker for predicting future metastasis in human cancers.

Metastasis is a major cause of mortality in cancer patients. However, the mechanisms governing the metastatic process remain elusive, and few accurate biomarkers exist for predicting whether metastasis will occur, something that would be invaluable for guiding therapy. We report here that the carboxypeptidase E gene (CPE) is alternatively spliced in human tumors to yield an N-terminal truncated protein (CPE-ΔN) that drives metastasis.

Observer variability in the interpretation of HER2/neu immunohistochemical expression with unaided and computer-aided digital microscopy.

Context: Observer variability in digital microscopy and the effect of computer-aided digital microscopy are underexamined areas in need of further research, considering the increasing use and future role of digital imaging in pathology. A reduction in observer variability using computer aids could enhance the statistical power of studies designed to determine the utility of new biomarkers and accelerate their incorporation in clinical practice.

Objectives: To quantify interobserver and intraobserver variability in immunohistochemical analysis of HER2/neu with digital microscopy and computer-aided digital microscopy, and to test the hypothesis that observer agreement in the quantitative assessment of HER2/neu immunohistochemical expression is increased with the use of computer-aided microscopy.

Detection of somatic mutations by high-resolution DNA melting (HRM) analysis in multiple cancers.

Identification of somatic mutations in cancer is a major goal for understanding and monitoring the events related to cancer initiation and progression. High resolution melting (HRM) curve analysis represents a fast, post-PCR high-throughput method for scanning somatic sequence alterations in target genes. The aim of this study was to assess the sensitivity and specificity of HRM analysis for tumor mutation screening in a range of tumor samples, which included 216 frozen pediatric small rounded blue-cell tumors as well as 180 paraffin-embedded tumors from breast, endometrial and ovarian cancers (60 of each).

Association of prion protein expression with pancreatic adenocarcinoma survival in the SEER residual tissue repository.

Pancreatic ductal adenocarcinoma (PDAC) is an important cause of cancer death with no clear prognostic biomarker. Expression of prion (PrP) has been reported to be a marker of poor prognosis in a series of Caucasian PDAC cases. We determined the prognostic value of PrP in a racially and geographically diverse population-based series of PDAC cases.

Systematic proteome analysis identifies transcription factor YY1 as a direct target of miR-34a.

MicroRNA 34a (miR-34a) is a potential tumor suppressor gene and has been identified as a miRNA component of the p53 network. To better understand the biological pathways involved in miR-34a action, a parallel global protein and mRNA expression profiling on miR-34a treated neuroblastoma cells (IMR32) was performed using isotope-coded affinity tags (ICAT) and Affymetrix U133plus2 microarray, respectively. Global profiling showed that miR-34a causes much smaller mRNA expression changes compared to changes at the protein level.