Tumor viability

Thirty-four patients vith advanced solid tumors were treated with CA-4-P receiving 167 infusions [47]. The drug CA-4-P was given weekly for 3 weeks followed by a gap of 1 week. Up to 40 mg/m, the only drug-related toxicity was tumor pain in 35%. Tumor pain was not considered a dose-limiting toxicity because it could be controlled by analgesics. Tumor viability and tumor blood flow were assessed by positron emission therapy (PET) and DCE-MRI. 

The traditional view of cancer as an anatomic disease is rapidly evolving into an understanding of cancer as a systemic molecular disease. More and more physicians now detect differences between anatomic masses by anatomic imaging and tumor viability by PET imaging of molecular processes. 

Dual phase, contrast-enhanced MRI with perfusion sequence will not only delineate the extent and viability of tumor but also serve as a baseline study to plan future treatment. A simple dual-phase MRI or CT is acceptable as well but inferior to MRI perfusion in quantifying viable tumor. In addition to information regarding tumor viability and morphology, cross-sectional provides information regarding the tumor s vascular supply and anatomy. For example, knowing the presence of portal vein thrombosis... 

For maximum benefit, patients should be seen at regular intervals, a perfusion MRl of the liver obtained (Figs. 10.7 and 10.8) and compared to the baseline or previous MRl. Six-week intervals between successive TACEs is currently the standard at our institution. Prior to each TACE the MRl will establish tumor viability (or necrosis). Necrosis is quantified as 0%-25%, 25%-50%, 50%-75%, and 75%-100% based on perfusion (or contrast enhancement) MRl. If no residual viable tumor is noted, a follow-up MRl is scheduled for 6 weeks later and no TACE is performed. Lack of satisfactory response after one TACE does not predict eventual response, and addihonal TACE should target the same tumor. We have observed many times patients having failed to respond to the first TACE, responding very favorably after the second or third... 

A massive body of evidence has already been presented clearly indicating that the medicinal plants of the Pacific Rim elaborate a broad array of cytotoxic substances. Most of these have been characterized using experimental procedures designed to examine the cytotoxicity of natural products against human tumor cell lines. These procedures involve in vitro screening where the viability of cultured cells after exposure to an extract or a purified substance is measured. 

For purposes of quality control, any cell preparation used in the screen (see below) needs to have a definitive or consensus diagnosis and grading determined by histological examination. Furthermore, tumor cell preparations must be at least 80% tumor cells (as determined by cytopathological examination), whereas normal cell preparations must be devoid of any tumor cells. Cell viability, determined by trypan-blue exclusion, must be a minimum of 70%, and the signal-to-noise ratios for a predetermined cell cluster concentration must be at least threefold. 

The supernatant was replaced after 3 days of exposure of cells (tumor and normal) to plant extracts and the cells were washed with PBS, then 500 pL MTT solution (0.25 mg/mL) was added to each well. The cells were washed after 3 h of incubation at 37 C, the formazan crystals formed in hving cells solubilized with 1 mL isopropanol, and the absorbance measured at 570 run with a Jasco UV-Vis spectrometer. Cell viability was expressed as a percentage of control treated with different concentrations of plant extracts. 

Tumor cells T11 and Vero cells viability after 72 hours of treatment with red onion extract... 

The tests for in vitro biocompatibility were performed on normal cells (Vero) and tumor cells (glioblastoma). No cytotoxicity was detected in cells (normal or tumor) cultured with red and white onion extracts at low concentrations (between 0% and 1%), the cell viability being aronnd 90%. At higher concentration, the viability decrease slowly at 80% (Fig. 41.4a). On the other hand, garlic extracts indnce toxicity both on normal and tnmor cells at very low concentrations (Fig. 41.4b). 

The presence of dietary carnosine in vitamin E-deficient rats was found to increase mammary tumor latency, while not affecting tumor incidence (Boissoneault et ah, 1998). Another beneficial effect of carnosine in relation to cancer has recently been reported carnosine was shown to inhibit metastasis of hepatocarcinoma SK-Hep-1 cells (Chung and Hu, 2008). Unlike the effects reported above, carnosine did not affect the viability of these cells but instead the dipeptide inhibited cell migration and invasion. The mechanism responsible apparently involves a decrease... 

The use of radiolabeled nucleosides as markers for anticancer activity has become a popular method due to the commercial availability of such compounds. The technique is based upon the knowledge that cells rendered unable to replicate or killed by the anticancer agent are unable to effectively incorporate nucleic acid precursors into their DNA or RNA structure. Therefore, a decrease in cell viability correlates with a decrease in radioactivity relative to a control cell population. Although specific procedures differ, the basic technique involves the incubation of tumor cells in the presence of the radiolabeled compound with or without anticancer agent followed by scintillation counting to determine the radioacti vity of the samples. 

The ability of a tumor cell to manufacture proteins is a result of intact DNA, RNA and biochemical intracellular mechanisms. Interference with any one of these structures or processes will result in the inability of the cell to produce required proteins. Hence, quantitation of tumor cell protein synthesis over a period of time may constitute a marker allowing determination of the efficacy of a macromolecular drug conjugate. The technique is based on the fact that decreased cell viability in the presence of radiolabeled amino adds correlates to a decrease in radioactivity relative to a control cell population. For example, 3H-leucine [175, 208], a mixture of [14C]-labeled amino acids [205], and 75Se-lenomethionine [54, 209] have been used to evaluate the activity of conjugates. 

Nanoparticles formulated with PLGA have been shown to be rapidly uptaken by the endothelial cells, the uptake was shown to depend on the nanoparticle concentration and the particles where mainly shown to localize in the cytoplasm (207). These nanoparticles were also shown to be biocompatible with the cells with no effect on cell viability (207). This is important due to the fact that endothelium is an important target for gene therapy in a number of disorders including angiogenesis, atherosclerosis, tumor growth, myocardial infarction, limb and cardiac ischemia, restenosis (207). 

The in vitro EBV-EA activation inhibition assay uses EBV genome-carrying lymphoblastoid cells (Raji cells derived from Burkitt s lymphoma). Many compounds which inhibit EBV-EA induction by tumor promoters have been demonstrated to act as inhibitors of tumor promotion in vivo [16,22,42,66-68]. This assay has an advantage since it obtaines the information on die cytotoxicity from the viability of Raji cells. High viability of these cells is an important factor in developing a compound for the chemoprevention of cancer [16]. So far, a number of triterpenoids and steroids from plants and their derivatives have been shown to possess... 

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