Hematogenous metastasis is still a poorly understood phenomenon. The rate-limiting step within the metastatic cascade is not yet clear although it may be estimated that the extravasation of circulating tumor cells is a step of crucial importance, as most tumor cells that are shed into circu ...
Accurate and early evaluation of tumor response to chemotherapy is a growing clinical need for optimal management of oncology patients. This is even more warranted by the lack of appropriate response evaluation criteria to new molecularly targeted anticancer therapies. In the two last d ...
The breadth and substance of anatomic (structural) and novel physiological (functional) imaging methods to noninvasively monitor and assess anticancer therapies continues to grow. Current techniques span several imaging disciplines including magnetic resonance (MR) im ...
Most anticancer agents act by inducing apoptosis in sensitive tumor cells. Hence, in many types of cancers, significant increase of tumor apoptosis after chemotherapy correlates with tumor chemosensitivity. Theoretically, a reliable evaluation of apoptotic changes, postche ...
The chemosensitivity of micrometastasis is an important factor in therapeutic approaches to micrometastasis. The protocol in this chapter presents procedures capable of examining the drug sensitivity of micrometastases to anticancer agents, especially those in the perito ...
Rodent models provide an important means of assessing antitumor activity vs toxicity for new cancer therapies. Tumors are often grown subcutaneously on the flank or back of animals, allowing accurate serial determination of tumor volume with calipers by measuring the tumors in three dim ...
Acute lymphoblastic leukemia (ALL) is predominantly a disease of the bone marrow that disseminates to multiple organ sites throughout the body and, without aggressive treatment, eventually results in multiorgan failure and death. Experimental models that mimic the disseminati ...
Currently-used rodent tumor models, including transgenic tumor models, or subcutaneously growing human tumors in immunodeficient mice, do not sufficiently represent clinical-cancer, especially with regard to metastasis and drug sensitivity. In order to obtain clinically ...
Metastatic disease, notably to the lungs, liver, bone, and brain, is the most common cause of death from breast cancer, despite advances in surgical and clinical management. Two basic principles govern the process of metastasis: first, that tumors are heterogeneous populations of cells; and s ...
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 ...