Highly aggressive, rapidly growing tumors are often hypoxic, owing to an inadequate supply relative to consumption of oxygen (O2) in the expanding tumor mass, or growth in tissues with physiologically low O2 concentrations (such as bone marrow). Selection of tumor cells that can grow or survi ...
We provide a detailed explanation of the procedure of the histoculture drug response assay (HDRA) with 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) end point among several modified HDRA procedures. Fresh surgical specimens are cut into approx 1- to 2-mm3 pie ...
The assessment of the degree or rate of cellular proliferation and cell viability is critical to the assessment of the effects of drugs, antibodies, or cytokines on both normal and malignant cell populations. This can be accomplished by either direct or indirect counting methods. Direct coun ...
For effective cancer chemotherapy, chemosensitivity testing of anticancer drugs should be performed using fresh surgical specimens obtained from the cancer. We have developed a new in vitro chemosensitivity test named the collagen gel droplet embedded culture drug sensitivity ...
The differential staining cytotoxicity (DiSC) assay is one of the total cell-kill assays that can be used for drug resistance testing. Numerous publications have demonstrated the clinical value of chemosensitivity testing with that assay (and similar ones). The DiSC assay is successf ...
The sulforhodamine B (SRB) assay was developed by Skehan and colleagues to measure drug-induced cytotoxicity and cell proliferation for large-scale drug-screening applications. Its principle is based on the ability of the protein dye sulforhodamine B to bind electrostatically a ...
The clonogenic cell survival assay determines the ability of a cell to proliferate indefinitely, thereby retaining its reproductive ability to form a large colony or a clone. This cell is then said to be clonogenic. A cell survival curve is therefore defined as a relationship between the dose of the ...
High-sensitivity cytotoxicity assays refer to assays that can detect high levels of cell kill, to many powers of 10, and that can detect, ideally, a single remaining viable cell. Two such assays are described here, which have been used with Raji B-lymphoma cells, and are applicable to other nonadher ...
This overview chapter presents the importance of chemosensitivity testing for screening new therapeutic agents, identifying patterns of chemosensitivity for different types of tumors, establishing patterns of cross-resistance and sensitivity in treatment naive and re ...
Chemosensitivity is affected by molecular biological factors, including factors related to the induction of apoptosis and the activity of proliferation. We analyzed immunohistochemically the expression of p53, Bcl-2, and Ki-67 in various types of cancers and assessed the correla ...
The development of reliable methods for the in vitro testing of sensitivity of cancer cells to various drugs has been a longstanding objective in cancer treatment. The development of individualized chemotherapy could minimize undesired toxic side effects and increase the chance of re ...
A method of assessing chemosensitivity of tissue utilizing tissue fluorescence and image analysis was implemented to provide a rapid and quantitative means of assessing the effect of drugs on tissue metabolic activity and proliferative capacity. The fluorescent microscopic im ...
ATP-binding cassette (ABC) drug efflux transporters limit intracellular concentration of their substrates by pumping them out of cell through an active, energy dependent mechanism. Several of these proteins have been originally associated with the phenomenon of multidrug resi ...
Millions of new cancer patients are diagnosed each year and over half of these patients die from this devastating disease. Thus, cancer causes a major public health problem worldwide. Chemotherapy remains the principal mode to treat many metastatic cancers. However, occurrence of cellu ...
Breast cancer resistance protein (BCRP/ABCG2) was discovered in multidrug resistant breast cancer cells having an ATP-dependent transport-based resistance phenotype. This ABC transporter functions (at least in part) as a xenobiotic protective mechanism for the organism: in t ...
A newly identified form of multidrug resistance (MDR) in tumor cells is presented, pertaining to the commonly encountered resistance of cancer cells to anticancer drug combinations at discrete drug:drug ratios. In vitro studies have revealed that whether anticancer drug combinati ...
The multidrug resistance (MDR) phenotype exhibited by cancer cells is believed to be the major barriers to successful chemotherapy in cancer patients. The major form of MDR phenotype is contributed by a group of ATP-binding cassette (ABC) drug transporters which include P-glycoprotein, ...
Chemotherapy remains the mainstay in the treatment and management of many cancers. However, this treatment modality is fraught with difficulties associated with toxicity and also the emergence of chemotherapy resistance is a considerable problem. Cancer scientists and oncolo ...
Modulation of P-glycoprotein (Pgp)-mediated transport has significant pharmacokinetic implications for Pgp substrates. Pharmacokinetic alterations may be at the systemic (blood concentrations), regional (organ or tissue concentrations), or local (intracellular c ...
The prominent role for the drug efflux pump ABCB1 (P-glycoprotein) in mediating resistance to chemotherapy was first suggested in 1976 and sparked an incredible drive to restore the efficacy of anticancer drugs. Achieving this goal seemed inevitable in 1982 when a series of calcium channel ...