Chemoresistance remains an unresolved problem in clinical oncology. Therefore it is impor tant to identify molecular factors that lead to an understanding of the mechanisms of drug resis tance in cancer cells. On the protein-expression level,this can be done using proteomics,which has ...
5-Fluorouracil (5-FU) is still a key drug in the treatment of various kinds of advanced cancer, including breast and gastrointestinal carcinomas. To predict the sensitivity of colorectal cancer to 5-FU, mRNA is extracted from surgically obtained cancer specimens and expression of thym ...
Fission and budding yeast have been regarded as valuable tools for studying several cellular processes in eukaryotic cells and have been exploited as model systems for the identification of determinants of chemosensitivity. Indeed, yeast mutants of DNA repair and cell cycle checkpoi ...
In an effort to identify genes involved in chemosensitivity and to evaluate the functional rela tionships between genes and anticancer drugs acting by the same mechanism, a supervised machine learning approach called support vector machine (SVM) is used to associate genes with any of five p ...
This chapter presents a protocol for using cDNA microarrays to acquire gene expression pro files that characterize anticancer drug sensitivity. The protocol includes steps for drug exposure, RNA isolation, preparation of fluorescently labeled samples, microarray hybridiza ...
Silicon sensor technologies, developed during the 1990s, allow measurement of extracellular chemical changes related to cell metabolism. Exposition of tumor cells in vitro to anticancer drugs modifies cell metabolism, making it possible to detect on-line with sensor chips patte ...
Telomerase, which is selectively expressed in germline or cancer cells, is a ribonucleoprotein polymerase that contains an integral RNA with a short template element that can compensate telomeric loss by synthesizing TTAGGG repeats at chromosome ends. Telomeres appear to be critic ...
The Bcl-2 family of proteins centrally regulates the cellular commitment to apoptosis (programmed cell death). Apoptosis, in turn, is critical for the development and homeostasis of multicellular organisms, and defects in apoptosis contribute to a broad range of human diseases and dis ...
Apoptosis is a distinct morphological and biochemical entity resulting in cell death, which occurs because of a variety of pathological and physiological stimuli. Chemotherapeutic agents, at least in part, result in cell death by inducing apoptosis. Quantitation of this process ena ...
The ultimate aim of cancer therapeutics is to eradicate tumor cells. Upon lethal exposure to chemotherapeutic agents, cells undergo apoptosis-an active, energy-requiring, programmed cell death. Apoptosis follows a well-orchestrated activation of cysteine proteases, known ...
A simple, sensitive, and reliable DNA diffusion assay for quantification of apoptosis is based on the principle that nuclear DNA of apoptotic cells have abundant alkali-labile sites and under alkaline conditions small pieces of DNA thus generated diffuse in agarose, giving the appearan ...
Chemotherapy induces injury to tumor cells, which subsequently die by a number of processes. One of those processes is apoptosis, and its measurement can be a useful tool to understanding the mechanisms of action of chemotherapy agents, drug resistance, and tumor biology. Cells undergoing a ...
Induction of tumor cell death by chemotherapeutic modalities often occurs in a cell cycle-dependent manner. It has also been observed that several regulatory proteins involved in tumor chemosensitivity and apoptosis are expressed periodically during the cell cycle progres sion. ...
The study of DNA damage at the chromosome level is an essential part of genetic toxicology because chromosomal mutation is an important event in carcinogenesis. The micronucleus assays have emerged as one of the preferred methods for assessing chromosome damage because they enable both c ...
Ceramide is a bioactive lipid involved in the induction of apoptosis and is the precursor to several sphingolipids, including sphingomyelin, the gangliosides, and sphingosine. Ceramide production is increased in response to stress and toxic agents. Because modulation of ceramide ...
The measurement of functional and phenotypic P-glycoprotein by flow cytometry is suitable for cells in suspension, and is particularly appropriate for blood and bone marrow cells. We describe a functional assay for P-glycoprotein using rhodamine 123, an assay for daunorubicin accum ...
Laser flow cytometry has been used for monitoring cellular retention of fluorescent drugs such as fluorescent anticancer antibiotics (e.g., doxorubicin) and fluorochromes used for the detection of cellular drug efflux and resistance (e.g., rhodamine 123, Hoechst 33342). Multi para ...
Drug resistance of tumor cells is recognized as the primary cause of failure of chemotherapeutic treatment of most human tumors. Although pharmacological factors-including inadequate drug concentration at the tumor site-can contribute to clinical resistance, cellular fact ...
Recurring chromosomal abnormalities are associated with distinct subtypes of leukemia or lymphoma that have unique morphologic, immunophenotypic, and clinical features, such as response to therapy (1–4). Thus, cytogenetic analysis of an individual’s malignant cells plays a ma ...
Genitourinary malignancies were diagnosed in over 250,000 U.S. men and women in the year 2000, and carcinomas of the prostate, kidney and urothelium accounted for over 20% of all adult malignancies (1). In the twenty-first century, oncologists and molecular biologists will be challenged to ex ...

