HER2 gene amplification in patients with breast cancer with equivocal IHC results.

Aims: Equivocal human epidermal growth factor receptor 2 protein (HER2) (2+) immunohistochemistry (IHC) is subject to significant interobserver variation and poses a challenge in obtaining a definitive positive or negative test result. This equivocal test result group accounts for approximately 15% of all tumours, and for optimal guidance of HER2 targeted therapy, a further analysis of quantification of gene copy number and amplification status is needed for patients with early or metastatic breast cancer.

Methods: 553 breast-cancer specimens with equivocal HER2 IHC(2+) test results were collected and subsequently centrally retested by chromogenic in situ hybridisation (CISH), and HER2 gene copy numbers per tumour cell nucleus were determined.

An Unexpected Detrimental Effect on the Incidence of Heel Pressure Ulcers After Local 5% DMSO Cream Application: A Randomized, Double-blind Study in Patients at Risk for Pressure Ulcers.

Unlabelled: Background. Ischemia-reperfusion injury and reactive oxygen species (ROS) are considered to play an important role in the pathogenesis of pressure ulcers (PU). Antioxidants may diminish the inflammation and damage of these ROS in pressure ulcer formation.

Is the distinction between superficial pressure ulcers and moisture lesions justifiable? A clinical-pathologic study.

Objective: Pressure ulcers are classified into 4 distinct stages, which allows comparisons between institutions and even countries. Recently, attempts have been made to single out so-called moisture lesions from the early stages of pressure ulcer lesions as a distinct entity.

Methods: To investigate the justification for this development, 14 histopathologic samples from patients with both incontinence and pressure ulcer lesions were studied in an attempt to delineate differences in the pathophysiology and histopathology.

Does glutamine-enriched parenteral nutrition really affect intestinal morphology and gut permeability?

Background: Nutritional depletion has been related to low glutamine levels in plasma and gut mucosa. This study was set up to investigate the effects of glutamine-enriched total parenteral nutrition on intestinal morphology and permeability.

Methods: Twenty-three depleted patients were randomized and after stabilization baseline measurements were performed.

Isolation of human antibodies to tumor-associated endothelial cell markers by in vitro human endothelial cell selection with phage display libraries.

Human antibodies selectively targeting angiogenic vessels hold great promise for the immunotherapy of human malignancies and can help to elucidate the molecular mechanisms regulating angiogenesis. By selecting a large antibody phage display library on proliferating stimulated HUVEC, we have isolated 15 human antibodies that bind to HUVEC in flow cytometric analysis, 11 of which target the vasculature of colorectal carcinomas as demonstrated by immunohistochemical analysis. The four most specific antibodies, TEM-A, TEM-C, TEM-M and TEM-Q, also stain the vasculature of a series of carcinomas derived from liver, ovary, kidney, bladder, lung and breast, and either react weakly or not all with the vasculature of corresponding normal tissues.

Simultaneous detection of apoptosis and proliferation in colorectal carcinoma by multiparameter flow cytometry allows separation of high and low-turnover tumors with distinct clinical outcome.

Background: Dukes C colorectal carcinoma is treated with adjuvant chemotherapy. Adjuvant treatment is not standard for patients with Dukes B tumors, even though about 20% of patients within this tumor stage die of recurrent disease. The authors investigated whether a novel method of simultaneous detection of apoptosis and proliferation would improve the assessment of prognosis in colorectal carcinoma patients, with the ultimate goal of accurately identifying patients eligible for adjuvant therapy.

Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability.

Background & Aims: Current models of colorectal adenoma to carcinoma progression do not fully reflect the genetic heterogeneity and complexity of the disease. The aim of the present study was to identify genetic changes discriminating adenomas that have progressed to carcinoma from adenomas that have not progressed, and to refine the current genetic models of colorectal adenoma to carcinoma progression, based on a genome-wide analysis of chromosomal aberrations.

Methods: Sixty-six nonprogressed colorectal adenomas, 46 progressed adenomas (malignant polyps), and 36 colorectal carcinomas were screened for chromosomal aberrations by comparative genomic hybridization, and for mutations in the adenomatous polyposis coli (APC) and K-ras gene.

Target validation for genomics using peptide-specific phage antibodies: a study of five gene products overexpressed in colorectal cancer.

Genomic approaches are providing a wealth of information on differential gene expression in cancer. To identify the most interesting genes amongst the many identified, high-throughput methods for analysis of genes at the translational level are required. We have used a rapid method for the in vitro selection of antibodies to peptide antigens for the generation of probes to 5 gene products that we have found to be overexpressed in colorectal cancer.

A panel of candidate tumor antigens in colorectal cancer revealed by the serological selection of a phage displayed cDNA expression library.

In the last few years it has been shown that the humoral immune response in cancer patients is a rich source of putative cancer vaccine candidates. To fully explore the complex information present within the Ab repertoire of cancer patients, we have applied a method, serological Ag selection, to molecularly define tumor Ags recognized by the humoral immune response in colorectal cancer (CRC). First, we built a cDNA display library by cloning a cDNA library from CRC cell line HT-29 for expression as a fusion protein with a filamentous phage minor coat protein, pVI.

K-ras mutations and RASSF1A promoter methylation in colorectal cancer.

Human cancer is characterized by genetic and epigenetic alterations. In this study we provide evidence for the interruption of Ras signaling in sporadic colorectal cancer (CRC) by either genetic activation of the K-ras oncogene or epigenetic silencing of the putative tumor suppressor gene RASSF1A. Paraffin embedded tumor tissue samples from 222 sporadic CRC patients were analysed for K-ras codon 12 and codon 13 activating mutations and RASSF1A promoter hypermethylation.

A human immunoglobulin G1 antibody originating from an in vitro-selected Fab phage antibody binds avidly to tumor-associated MUC1 and is efficiently internalized.

We describe the engineering and characterization of a whole human antibody directed toward the tumor-associated protein core of human MUC1. The antibody PH1 originated from the in vitro selection on MUC1 of a nonimmune human Fab phage library. The PH1 variable genes were reformatted for expression as a fully human IgG1.