A Companion Diagnostic With Significant Clinical Impact in Treatment of Breast and Gastric Cancer.

The development of trastuzumab (Herceptin) was one of the most significant cancer drug development projects of the 20th century. Not only was it a scientific and medical achievement but it also paved the way for the drug-diagnostic codevelopment model, where a predictive biomarker assay is developed in parallel to the drug. One of the challenges in the development of trastuzumab was to select the right patient population likely to respond and here, it was critical to have access to an accurate, robust and reliable assay for detection of HER2 overexpression in tumors.

Molecular prediction of adjuvant cisplatin efficacy in Non-Small Cell Lung Cancer (NSCLC)-validation in two independent cohorts.

Introduction: Effective predictive biomarkers for selection of patients benefiting from adjuvant platinum-based chemotherapy in non-small cell lung cancer (NSCLC) are needed. Based on a previously validated methodology, molecular profiles of predicted sensitivity in two patient cohorts are presented.

Methods: The profiles are correlations between in vitro sensitivity to cisplatin and vinorelbine and baseline mRNA expression of the 60 cell lines in the National Cancer Institute panel.

Independent validation of a model using cell line chemosensitivity to predict response to therapy.

Background: Methods using cell line microarray and drug sensitivity data to predict patients' chemotherapy response are appealing, but groups may be reluctant to release details to preserve intellectual property. Here we describe a case study to validate predictions while treating the methods as a "black box."

Methods: Medical Prognosis Institute (MPI) constructed cell-line-derived sensitivity scores (SSs) and combined scores (CSs) that incorporate clinical variables.

Market access challenges in the EU for high medical value diagnostic tests.

The clinical utility and medico-economic value of several personalized diagnostic tests has been well described in the literature. Development of such tests, including generation of the necessary supportive clinical validation data, is a complex and expensive endeavor. In general, sponsors of such tests lack sufficient clarity on appropriate reimbursement and regulatory pathways to provide the clear development framework necessary to incentivize the required level of investment.

Development of standard estrogen and progesterone receptor immunohistochemical assays for selection of patients for antihormonal therapy.

Estrogen receptor (ER) and progesterone receptor (PR) status in breast carcinomas are considered validated predictive factors for selecting patients for antihormonal therapy. Published surveys have shown a significant rate of disagreement and lack of reproducibility of immunohistochemistry (IHC) results from laboratories around the world. To address these limitations IHC assays for ER and PR were developed using characterized reagents, after careful calibration of the sensitivity and specificity to match established assays previously validated in large clinical studies.

Prostein expression is highly restricted to normal and malignant prostate tissues.

Background: Prostein is a recently described molecule expressed at the mRNA level in a prostate-specific manner. A murine monoclonal antibody was developed, characterized, and used to evaluate the expression of prostein protein in prostatic, other normal tissue and tumor samples.

Methods: The murine anti-prostein monoclonal antibody 10E3-G4-D3 was generated using recombinant prostein.

Localization of serglycin in human neutrophil granulocytes and their precursors.

Serglycin is a major proteoglycan of hematopoietic cells. It is thought to play a role in the packaging of granule proteins in human neutrophil granulocytes. The presence of serglycin in myeloid cells has been demonstrated only at the transcriptional level.

The prognostic value of epidermal growth factor receptor is related to tumor differentiation and the overall treatment time of radiotherapy in squamous cell carcinomas of the head and neck.

Accelerated repopulation in head-and-neck carcinomas might be related to the expression of proliferative factors such as epidermal growth factor receptor (EGFr). The present study focuses on the prognostic value of EGFr for T-site control and the relation to tumor cell differentiation and overall treatment time. We studied 336 patients treated with primary radiotherapy using 66-68 Gy, 2 Gy per fraction and overall treatment times of 912, 612, or 512 weeks.

Defensin-rich granules of human neutrophils: characterization of secretory properties.

The various granule subtypes of the human neutrophil differ in propensity for exocytosis. As a rule, granules formed at late stages of myelopoiesis have a higher secretory potential than granules formed in more immature myeloid cells. Neutrophils contain four closely related alpha-defensins, which are stored in a subset of azurophil granules.