Toward predicting CYP2D6-mediated variable drug response from gene sequencing data.

Pharmacogenomics is a key component of personalized medicine that promises safer and more effective drug treatment by individualizing drug choice and dose based on genetic profiles. In clinical practice, genetic biomarkers are used to categorize patients into *-alleles to predict CYP450 enzyme activity and adjust drug dosages accordingly. However, this approach leaves a large part of variability in drug response unexplained.

Repurposing of Diagnostic Whole Exome Sequencing Data of 1,583 Individuals for Clinical Pharmacogenetics.

For ~ 80 drugs, widely recognized pharmacogenetics dosing guidelines are available. However, the use of these guidelines in clinical practice remains limited as only a fraction of patients is subjected to pharmacogenetic screening. We investigated the feasibility of repurposing whole exome sequencing (WES) data for a panel of 42 variants in 11 pharmacogenes to provide a pharmacogenomic profile.

Joint Assimilation of Leaf Area Index and Soil Moisture from Sentinel-1 and Sentinel-2 Data into the WOFOST Model for Winter Wheat Yield Estimation.

It is well known that timely crop growth monitoring and accurate crop yield estimation at a fine scale is of vital importance for agricultural monitoring and crop management. Crop growth models have been widely used for crop growth process description and yield prediction. In particular, the accurate simulation of important state variables, such as leaf area index (LAI) and root zone soil moisture (SM), is of great importance for yield estimation.

Flexible and Scalable Full-Length CYP2D6 Long Amplicon PacBio Sequencing.

Cytochrome P450 2D6 (CYP2D6) is among the most important genes involved in drug metabolism. Specific variants are associated with changes in the enzyme's amount and activity. Multiple technologies exist to determine these variants, like the AmpliChip CYP450 test, Taqman qPCR, or Second-Generation Sequencing, however, sequence homology between cytochrome P450 genes and pseudogene CYP2D7 impairs reliable CYP2D6 genotyping, and variant phasing cannot accurately be determined using these assays.

CCR 20th Anniversary Commentary: Paving the Way for Circulating Tumor Cells.

Cancer cells can enter the bloodstream, form distant metastases, and ultimately lead to death. A study by Allard and colleagues, which was published in the October 15, 2004, issue of Clinical Cancer Research, concluded that the CellSearch system could be used as a reliable tool to investigate circulating tumor cells and their clinical utility, and it spurred a still-growing interest in the field.

Combining clinical assessment and the Risk of Ovarian Malignancy Algorithm for the prediction of ovarian cancer.

Objectives: ACOG guidelines for the evaluation of women with a pelvic mass employ a combination of physical exam, imaging, and CA125 to guide physicians in the triage of women to gynecologic oncologists. We studied the use of ROMA with clinical assessment for cancer risk assessment in women with a pelvic mass.

Methods: This was a prospective, multicenter trial evaluating women with a pelvic mass who had an initial clinical risk assessment (ICRA) performed by a generalist.

Comparison of a novel multiple marker assay vs the Risk of Malignancy Index for the prediction of epithelial ovarian cancer in patients with a pelvic mass.

Objective: We sought to compare the Risk of Malignancy Index (RMI) to the Risk of Ovarian Malignancy Algorithm (ROMA) to predict epithelial ovarian cancer (EOC) in women with a pelvic mass.

Study Design: In all, 457 women with imaging results from ultrasound, computed tomography, magnetic resonance imaging, and serum HE4 and CA125 determined prior to surgery for pelvic mass were evaluable. RMI values were determined using CA125, imaging score, and menopausal status.

Protein profiling of pleural effusions to identify malignant pleural mesothelioma using SELDI-TOF MS.

Diagnosis of malignant pleural mesothelioma (MM) is limited. Novel proteomic techno_logies can be utilized to discover changes in expression of pleural proteins that might have diagnostic value. The objective of this study was to detect protein profiles that could be used to identify malignant pleural mesothelioma with surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS).

A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass.

Introduction: Patients diagnosed with epithelial ovarian cancer (EOC) have improved outcomes when cared for at centers experienced in the management of EOC. The objective of this trial was to validate a predictive model to assess the risk for EOC in women with a pelvic mass.

Methods: Women diagnosed with a pelvic mass and scheduled to have surgery were enrolled on a multicenter prospective study.

Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus.

Objective: Tumor markers with increased sensitivity and specificity for endometrial cancer are needed to help monitor response to therapy and to detect recurrent disease. Currently, the tumor maker CA125 is utilized in this role with limited value. The objectives of this study were to examine the levels of several novel tumor markers HE4, SMRP, CA72.

The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass.

Objectives: The CA125 tumor marker is used to help predict the presence of ovarian cancer in patients with an adnexal mass. Because elevated CA125 levels occur in many benign gynecologic conditions, we set out to identify other novel biomarkers that would increase the sensitivity and specificity of CA125.

Methods: Serum and urine samples were obtained preoperatively from women undergoing surgery for an adnexal mass.

MESOMARK(®) in vitro diagnostic test for mesothelioma.

Mesothelioma is a highly progressive tumor with a poor prognosis. In this article, the authors give a thorough introduction into and evaluation of the MESOMARK(®) in vitro test - the only blood test for the management of patients with mesothelioma approved by the US FDA. In Europe, Australia, New Zealand and Canada, the test is approved or licensed for the measurement of the soluble mesothelin, also termed as soluble mesothelin-related peptides.

MESOMARK: a potential test for malignant pleural mesothelioma.

Background: Soluble mesothelin-related peptides (SMRP)have been reported to be potential biomarkers for malignant pleural mesothelioma (MPM). We report analytical and preliminary clinical studies of MESOMARK, a quantitative assay for SMRP.

Methods: The MESOMARK assay is a 2-step immunoenzymatic assay in an ELISA format with a 6-point calibration curve (0-32 nmol/L).

Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival.

Purpose: We reported previously that >or=5 circulating tumor cells (CTC) in 7.5 mL blood at baseline and at first follow-up in 177 patients with metastatic breast cancer (MBC) were associated with poor clinical outcome. In this study, additional follow-up data and CTC levels at subsequent follow-up visits were evaluated.

Circulating tumor cells predict survival in patients with metastatic prostate cancer.

Objectives: To determine whether circulating tumor cells (CTCs) predict for survival in patients with metastatic prostate cancer (PCa) and to compare its prognostic abilities with other clinical factors.

Methods: Blood samples from 37 patients with metastatic PCa were analyzed for CTCs. CTCs were enriched from 7.

Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer.

Purpose: Metastatic breast cancer (MBC) is incurable; its treatment is palliative. We investigated whether the presence of circulating tumor cells (CTCs) predicts treatment efficacy, progression-free survival (PFS), and overall survival (OS) in patients with newly diagnosed MBC who were about to start first-line therapy.

Patients And Methods: One hundred seventy-seven patients with measurable MBC were enrolled onto a prospective study.

Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases.

Purpose: The purpose of this study was to determine the accuracy, precision, and linearity of the CellSearch system and evaluate the number of circulating tumor cells (CTCs) per 7.5 mL of blood in healthy subjects, patients with nonmalignant diseases, and patients with a variety of metastatic carcinomas.

Experimental Design: The CellSearch system was used to enumerate CTCs in 7.

Circulating tumor cells, disease progression, and survival in metastatic breast cancer.

Background: We tested the hypothesis that the level of circulating tumor cells can predict survival in metastatic breast cancer.

Methods: In a prospective, multicenter study, we tested 177 patients with measurable metastatic breast cancer for levels of circulating tumor cells both before the patients were to start a new line of treatment and at the first follow-up visit. The progression of the disease or the response to treatment was determined with the use of standard imaging studies at the participating centers.

The rise of the rhizosolenid diatoms.

The 18S ribosomal DNA molecular phylogeny and lipid composition of over 120 marine diatoms showed that the capability to biosynthesize highly branched isoprenoid (HBI) alkenes is restricted to two specific phylogenetic clusters, which independently evolved in centric and pennate diatoms. The molecular record of C25 HBI chemical fossils in a large suite of well-dated marine sediments and petroleum revealed that the older cluster, composed of rhizosolenid diatoms, evolved 91.5 +/- 1.

Effects of auxosporulation on distributions of C(25) and C(30) isoprenoid alkenes in Rhizosolenia setigera.

The effect of life cycle on the distributions of C(25) and C(30) highly branched isoprenoid (HBI) alkene lipids has been investigated for the marine diatom Rhizosolenia setigera. The concentrations of the C(30) compounds are largely independent of the cell volume, though the ratios of the individual isomers possessing five and six double bonds show a dependence on the position of the cell during its life cycle, especially during auxosporulation. In contrast to the C(30) pseudo-homologues, the C(25) isomers are not always detected in cultures of R.

Factors influencing the distributions of polyunsaturated terpenoids in the diatom, Rhizosolenia setigera.

Polyunsaturated highly branched isoprenoid (HBI) hydrocarbon distributions of laboratory cultures of five strains of the planktonic diatom Rhizosolenia setigera (Brightwell) are shown herein to be highly variable. Some strains produced both haslenes with from three to five double bonds and rhizenes. The haslenes comprised not only Delta5 alkenes but also those with C7(20) unsaturation, including hasla-7(20),9E,Z, 23-trienes and hasla-7(20),9E,Z-13, 23-tetraenes.

Variable stereochemistry in highly branched isoprenoids from diatoms.

C(25) highly branched isoprenoid (HBI) alkenes are ubiquitous lipids found in geochemical samples around the globe. The origins of these widespread geochemicals are believed to be restricted to a limited number of diatoms, including Haslea ostrearia (and related species), Rhizosolenia setigera, and Pleurosigma intermedium. The unsaturation of the HBI alkenes ranges from 2-6 in different species and cultures.