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BACKGROUND RRM1, the regulatory subunit of ribonucleotide reductase, is involved in carcinogenesis, tumor progression, and the response of non-small-cell lung cancer to treatment. METHODS We developed an automated quantitative determination of the RRM1 protein in routinely processed histologic specimens. In these specimens, we measured the expression of(More)
BACKGROUND New tumor markers and markers of tumor progression are needed for improved staging and for better assessment of treatment of many cancers. Gene expression profiling techniques offer the opportunity to discover such markers. We investigated the feasibility of sample pooling strategy in combination with a novel analysis algorithm to identify(More)
The pH of solid tumors is acidic due to increased fermentative metabolism and poor perfusion. It has been hypothesized that acid pH promotes local invasive growth and metastasis. The hypothesis that acid mediates invasion proposes that H(+) diffuses from the proximal tumor microenvironment into adjacent normal tissues where it causes tissue remodeling that(More)
We investigate a three-dimensional multiscale model of vascular tumour growth, which couples blood flow, angiogenesis, vascular remodelling, nutrient/growth factor transport, movement of, and interactions between, normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. In particular, we determine how the domain size, aspect(More)
BACKGROUND Thymidylate synthase (TS) is important for maintenance of the intracellular thymidine pool, which is crucial for DNA synthesis and repair. TS messenger RNA and protein levels are predictive of response to 5-fluorouracil-containing therapy for patients with colorectal cancer and gastric cancer. High levels of expression of 2 other genes important(More)
INTRODUCTION One-size-fits-all chemotherapy does not improve survival in patients with small cell lung cancer (SCLC). Excision repair cross-complementing group 1 (ERCC1), ribonucleotide reductase 1 (RRM1), thymidylate synthase (TS), and topoisomerase 2alpha (Topo2alpha) expression levels are predictive of chemotherapeutic efficacy in some malignancies. Our(More)
Identifying molecular markers for colon cancer is a top priority. Using a pooled sample approach with Affymetrix GeneChip technology, we assayed colon cancers derived from a series of clinical stages to identify molecular markers of potential prognostic value. Of 12000 genes assessed, osteopontin emerged as the leading candidate tumor progression marker.(More)
The adenomatous polyposis coli (APC) gene, a member of the WNT pathway, has been shown to assign intestinal epithelial cells to a program of proliferation or differentiation through regulation of the beta-catenin/TCF-4 complex. Wild-type APC, in certain cellular contexts, appears to induce differentiation and apoptosis, although mutant forms of APC, known(More)
Clusterin is a widely expressed glycoprotein that has been paradoxically observed to have both pro- and antiapoptotic functions. Recent reports suggest this apparent dichotomy of function may be related to two different isoforms, one secreted and cytoplasmic, the other nuclear. To clarify the functional role of clusterin in regulating apoptosis, we examined(More)
Despite the great progress that has been made in understanding cancer biology and the potential molecular targets for its treatment, the majority of drugs fail in the clinical trials. This may be attributed (at least in part) to the complexity of interstitial drug transport in the patient's body, which is hard to test experimentally. Similarly, recent(More)