Targeted Cox2 gene deletion in intestinal epithelial cells decreases tumorigenesis in female, but not male, ApcMin/+ mice.

Mice heterozygous for mutations in the adenomatous polyposis coli gene (Apc(+/-) mice) develop intestinal neoplasia. Apc(+/-) tumor formation is thought to be dependent on cyclooxygenase 2 (COX2) expression; both pharmacologic COX2 inhibition and global Cox2 gene deletion reduce the number of intestinal tumors in Apc(+/-) mice. COX2 expression is reported in epithelial cells, fibroblasts, macrophages and endothelial cells of Apc(+/-) mouse polyps.

Defining the critical-sized defect in a rat segmental mandibulectomy model.

Importance: Advances in tissue engineering offer potential alternatives to current mandibular reconstructive techniques; however, before clinical translation of this technology, a relevant animal model must be used to validate possible interventions.

Objective: To establish the critical-sized segmental mandibular defect that does not heal spontaneously in the rat mandible.

Design And Setting: Prospective study of mandibular defect healing in 29 Sprague-Dawley rats in an animal laboratory.

Association between tumor-associated macrophage infiltration, high grade prostate cancer, and biochemical recurrence after radical prostatectomy.

Background: Tumor-associated macrophages (TAMs) are a key component of the inflammatory microenvironment. Their role in prostate cancer development and progression remains unclear. We examined whether the amount of TAMs in prostate cancer is: 1) higher than prostatic intraepithelial neoplasia (PIN) and benign tissue 2) associated with poorly differentiated disease, and 3) predictive of biochemical recurrence among surgically treated men.

Effect of a low-fat fish oil diet on proinflammatory eicosanoids and cell-cycle progression score in men undergoing radical prostatectomy.

We previously reported that a 4- to 6-week low-fat fish oil (LFFO) diet did not affect serum insulin-like growth factor (IGF)-1 levels (primary outcome) but resulted in lower omega-6 to omega-3 fatty acid ratios in prostate tissue and lower prostate cancer proliferation (Ki67) as compared with a Western diet. In this post hoc analysis, the effect of the LFFO intervention on serum pro-inflammatory eicosanoids, leukotriene B4 (LTB4) and 15-S-hydroxyeicosatetraenoic acid [15(S)-HETE], and the cell-cycle progression (CCP) score were investigated. Serum fatty acids and eicosanoids were measured by gas chromatography and ELISA.

Preoperative cardiac variables of diastolic dysfunction and clinical outcomes in lung transplant recipients.

Background. Orthotopic lung transplantation is now widely performed in patients with advanced lung disease. Patients with moderate or severe ventricular systolic dysfunction are typically excluded from lung transplantation; however, there is a paucity of data regarding the prognostic significance of abnormal left ventricular diastolic function and elevated pretransplant pulmonary pressures.

Modification of hematopoietic stem/progenitor cells with CD19-specific chimeric antigen receptors as a novel approach for cancer immunotherapy.

Chimeric antigen receptors (CARs) against CD19 have been shown to direct T-cells to specifically target B-lineage malignant cells in animal models and clinical trials, with efficient tumor cell lysis. However, in some cases, there has been insufficient persistence of effector cells, limiting clinical efficacy. We propose gene transfer to hematopoietic stem/progenitor cells (HSPC) as a novel approach to deliver the CD19-specific CAR, with potential for ensuring persistent production of effector cells of multiple lineages targeting B-lineage malignant cells.

Role of pancreatic cancer-derived exosomes in salivary biomarker development.

Recent studies have demonstrated that discriminatory salivary biomarkers can be readily detected upon the development of systemic diseases such as pancreatic cancer, breast cancer, lung cancer, and ovarian cancer. However, the utility of salivary biomarkers for the detection of systemic diseases has been undermined due to the absence of the biological and mechanistic rationale as to why distal diseases from the oral cavity would lead to the development of discriminatory biomarkers in saliva. Here, we examine the hypothesis that pancreatic tumor-derived exosomes are mechanistically involved in the development of pancreatic cancer-discriminatory salivary transcriptomic biomarkers.

New methods for ALK status diagnosis in non-small-cell lung cancer: an improved ALK immunohistochemical assay and a new, Brightfield, dual ALK IHC-in situ hybridization assay.

Introduction: The demonstration of anaplastic lymphoma kinase (ALK) positivity in non-small-cell lung cancer (NSCLC) has been hindered by the technical complexity and interpretative challenges of fluorescence in situ hybridization methods for detection of ALK gene rearrangement and by the inadequate sensitivity of existing immunohistochemistry (IHC) methods for ALK protein detection. In this study, we sought to increase the sensitivity of ALK IHC detection and to develop a brightfield assay for concurrent detection of ALK protein expression and ALK gene rearrangement.

Methods: We developed a horseradish peroxidase-based IHC detection system using the novel, nonendogenous hapten 3-hydroxy-2-quinoxaline (HQ) and tyramide.

Correlation of a novel noninvasive tissue oxygen saturation monitor to serum central venous oxygen saturation in pediatric patients with postoperative congenital cyanotic heart disease.

Using a novel noninvasive, visible-light optical diffusion oximeter (T-Stat VLS Tissue Oximeter; Spectros Corporation, Portola Valley, CA) to measure the tissue oxygen saturation (StO2) of the buccal mucosa, the correlation between StOz and central venous oxygen saturation (ScvO2) was examined in children with congenital cyanotic heart disease undergoing a cardiac surgical procedure. Paired StO2 and serum ScvO2 measurements were obtained postoperatively and statistically analyzed for agreement and association. Thirteen children (nine male) participated in the study (age range, 4 days to 18 months).

Mutation-specific antibody detects mutant BRAFV600E protein expression in human colon carcinomas.

Background: A point mutation (V600E) in the BRAF oncogene is a prognostic biomarker and may predict for nonresponse to anti-EGFR antibody therapy in patients with colorectal carcinoma. BRAFV600E mutations are frequently detected in tumors with microsatellite instability and indicate a sporadic origin. We used a mutation-specific antibody to examine mutant BRAFV600E protein expression and its concordance with BRAFV600E mutation data.

Bone morphogenetic protein-2-impregnated biomimetic scaffolds successfully induce bone healing in a marginal mandibular defect.

Objectives/hypothesis: To test the osteoregenerative potential and dosing of bone morphogenetic protein-2 (BMP-2)-impregnated biomimetic scaffolds in a rat model of a mandibular defect.

Study Design: Prospective study using an animal model.

Methods: Varied doses of BMP-2 (0.

Another look at follicular lymphoma: immunophenotypic and molecular analyses identify distinct follicular lymphoma subgroups.

Aims: The aim of this study was to analyse the immunophenotypic and molecular features of a large series of follicular lymphomas, focusing in particular on atypical cases that fail to express CD10 and/or bcl-2. Such cases present diagnostic pitfalls, especially with regard to the differential diagnosis from follicular hyperplasia and marginal zone B-cell lymphoma. Therefore, we also included an immunohistochemical evaluation of stathmin, which is strongly expressed by germinal centre B cells, as a putative new marker for follicular lymphomas, particularly those with an atypical phenotype.

Bright-field in situ hybridization methods to discover gene amplifications and rearrangements in clinical samples.

Brightfield in situ hybridization (BISH) applications have significant advantages over traditional fluorescence in situ hybridization (FISH). BISH slides can be analyzed using a regular microscope while FISH slides require the use of a specialized fluorescence microscope. BISH slides allow observers for correlating the gene status (gene amplifications, gene rearrangements, and gene deletions) and tissue morphology better than FISH slides.

Sinonasal rhabdomyosarcoma: prognostic factors and treatment outcomes.

Background: Despite the improvement in survival of pediatric patients with rhabdomyosarcoma, the outcome of patients with sinonasal rhabdomyosarcoma is poor and has not significantly changed. Since few institutions have extensive experience with sinonasal rhabdomyosarcoma in children and adults, our objective was to determine prognostic factors and treatment outcomes for this rare malignancy.

Methods: A retrospective review was performed of consecutive patients with sinonasal rhabdomyosarcoma treated at our institution from 1992 to 2012.

Acute liver failure in an obstetric patient: challenge of critical care for 1 patient with 2 subspecialty needs.

Acute fatty liver of pregnancy is a rare and life-threatening disease associated with a defect in fatty acid metabolism in the fetus that causes liver disease in the mother. Prompt diagnosis and management are critical to the outcome of both the mother and the fetus and require involvement of several medical specialties, including hepatology, obstetrics, and, possibly, critical care. The included case study describes a woman with acute fatty liver of pregnancy decompensating to acute liver failure complicated by encephalopathy, cerebral edema, and intracranial hypertension.

Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma.

Abnormalities of the MYC oncogene on chromosome 8 are characteristic of Burkitt lymphoma and other aggressive B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We recently described a colorimetric in situ hybridization (CISH) method for detecting extra copies of the MYC gene in DLBCL and the frequent occurrence of excess copies of discrete MYC signals in the context of diploidy or polyploidy of chromosome 8, which correlated with increased mRNA signals. We further observed enlarged MYC signals, which were counted as a single gene copy but, by their dimension and unusual shape, likely consisted of "clusters" of MYC genes.

Insulin-like growth factor-1 receptor protein expression and gene copy number alterations in non-small cell lung carcinomas.

Insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor implicated in the pathogenesis of several malignancies and is potentially an attractive target for anticancer treatment. In this study, we included 379 patients who underwent surgical resection (179 diagnosed as having adenocarcinoma [ADC]; 150, squamous cell carcinoma [SCC]; 41, sarcomatoid carcinoma and 9, large cell carcinoma). IGF-1R expression and gene copy number were assessed by immunohistochemistry and bright-field in situ hybridization (BISH), respectively.

Diagnostic value of sentinel lymph node biopsy in head and neck cancer: a meta-analysis.

This study aimed to evaluate the diagnostic reliability of sentinel lymph node biopsy in patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx by reviewing the published literature. A systematic literature review was performed using MEDLINE from 1970 to 2011. With Boolean search strings, search terms included sentinel node, supraglottic, supraglottis, tongue, head and neck, oral, pharynx, laryngeal, and larynx.

Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis.

Protein expression and gene copy number changes of receptor tyrosine kinase in thymomas and thymic carcinomas.

Background: Insulin-like growth factor-1 receptor (IGF-1R), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-type 2 (HER2), and c-Met are members of the receptor tyrosine kinases (RTKs). The associations between the RTK status [protein expression and gene copy number (GCN)] and patient characteristics and between the RTK status and prognosis remain undetermined.

Materials And Methods: The study included 140 patients who underwent surgery for thymic tumors.

A gene-protein assay for human epidermal growth factor receptor 2 (HER2): brightfield tricolor visualization of HER2 protein, the HER2 gene, and chromosome 17 centromere (CEN17) in formalin-fixed, paraffin-embedded breast cancer tissue sections.

Background: The eligibility of breast cancer patients for human epidermal growth factor receptor 2 (HER2)-directed therapies is determined by the HER2 gene amplification and/or HER2 protein overexpression status of the breast tumor as determined by in situ hybridization (ISH) or immunohistochemistry (IHC), respectively. Our objective was to combine the US Food and Drug Administration (FDA)-approved HER2 & chromosome 17 centromere (CEN17) brightfield ISH (BISH) and HER2 IHC assays into a single automated HER2 gene-protein assay allowing simultaneous detection of all three targets in a single tissue section.

Methods: The HER2 gene-protein assay was optimized using formalin-fixed, paraffin-embedded (FFPE) samples of the xenograft tumors MCF7 [HER2 negative (non-amplified gene, protein negative)] and Calu-3 [HER2 positive (amplified gene, protein positive)].

Partial plasma cell differentiation as a mechanism of lost major histocompatibility complex class II expression in diffuse large B-cell lymphoma.

Loss of major histocompatibility complex class II (MHC II) expression is associated with poor patient outcome in diffuse large B-cell lymphoma (DLBCL). As MHC II molecules are lost with plasmacytic differentiation in normal cells, we asked whether MHC II loss in DLBCL is associated with an altered differentiation state. We used gene expression profiling, quantum dots, and immunohistochemistry to study the relationship between MHC II and plasma cell markers in DLBCL and plasmablastic lymphoma (PBL).

Liver transplantation: issues and nursing care requirements.

Liver transplantation has evolved into an accepted treatment for many suffering from end-stage liver failure. The complex nature of the liver results in every organ system being impacted by either the failing or the transplanted liver. Organ shortage remains problematic, and work to ensure maximizing the organ donor pool as well as the success of each organ transplant continues.

Bright-field dual-color chromogenic in situ hybridization for diagnosing echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase-positive lung adenocarcinomas.

Introduction: A subset of lung cancers harbors an EML4-ALK (echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase) gene fusion, and detecting this subset may hold therapeutic implications. Many prior studies used fluorescence in situ hybridization (FISH) analysis for this detection, but FISH may have disadvantages including signal decay and dark-field examination that may obscure tissue architecture. In this study, we explored the potential of the ALK-break-apart chromogenic in situ hybridization (CISH) method to detect ALK-rearranged lung cancer.