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Cancer Chemotherapy and Pharmacology, 1992
In the present study a slightly modified MTT assay was used in conjunction with cell counting to determine the antiproliferative efficacy of N-(2-chloroethyl)-Nnitroso-N'-2-hydroxyethylurea (HECNU), vinblastine, and hexadecylphosphocholine (HPC) in a panel of six tumor cell lines. This panel consisted of two human (MDA-MB231, MCF-7) and two rodent (1/C2, 1/C32) mammarycarcinoma cell lines as well as of two tumor cell lines of gastrointestinal origin (HT-29, KB). It was shown that the use of acid isopropanol as a solvent of the formazan crystals produced correlations between cell number and absorption that were as good as, if not better than, those seen after dimethylsulfoxide (DMSO) application. The optimal period of incubation with the MTT dye was 2 h. A comparison of the antiproliferative activity of HECNU revealed that the HT-29 cell line was most resistant [50% inhibition concentration (ICs0), 138.7 gmol/l], followed by MCF-7 cells (ICs0, 127.7 gmol/1), whereas MDA-MB231 cells showed the highest sensitivity (ICs0, 6 gmol/1). Vinblastine induced the highest (MCF-7 cells; ICs0, 0.68 nmol/1) and the lowest (1/C2 cells; ICs0, 7.69 nmol/1) degrees of growth inhibition in cell lines derived from mammary carcinoma. This contrasted with the activity of HPC, which was considerably less effective in the four mammary-carcinoma cell lines (ICs0 from 29.4 to 69.9 gmol/1) than in the two cell lines of gastrointestinal origin (ICs0, 1.9 mad 3.1 gmolB). Interestingly, treatment with HPC stimulated the growth of 1/C32 cells in the lower dose range. After treatment with HECNU, the average ICs0 value determined in the MTT assay was 2.4-fold that disclosed by cell counting, whereas the average values found for HPC and vinblastine by both methods corresponded
Comparison of in vivo acute lethal potency and in vitro cytotoxicity of 48 chemicals
Cell Biology and Toxicology, 1992
The cytotoxicity of 48 compounds included in the MEIC (Multicenter Evaluation of In Vitro Cytotoxicity) list was determined in cultures of rat hepatocytes, McCoy, and MDBK cells. The average minimum concentration of each compound inducing cytotoxicity was measured in each cell type. The cytotoxicity values were then compared with published oral LD50 values for rats and mice. The logarithmic transformation of in vivo toxic doses and the corresponding in vitro cytotoxic concentrations showed a statistically significant correlation between the in vitro and in vivo values. The results show that an accurate in vivo LD50 dose could be predicted from in vitro data for at least 75% of the selected compounds. It is hoped that this finding will not only stimulate others to pursue in vitro technique but will eventually lead to elimination of the in vivo LD50 test.
Toxicities of anticancer drugs and its management
International Journal of Basic & Clinical Pharmacology, 2012
Common toxicities encountered are haematological, gastrointestinal, skin and hair follicle toxicity, nervous system toxicity, local toxicity, metabolic abnormalities, hepatic toxicity, urinary tract toxicity, cardiac toxicity, pulmonary toxicity, gonadal toxicity etc. 3 These toxicities, drugs causing this and management of these toxicities are discussed in subsequent sections of this paper. HAEMATOLOGICAL TOXICITY Peripheral cytopenia from bone marrow suppression is a frequent dose limiting side effect of chemotherapy and can manifest as acute and chronic marrow damage. 4 Chemotherapy may result in the destruction of activity of proliferating haematopoietic precursor cells, leading to deprivation of formed elements, and incidence of life threatening haemorrhage and infection. 5 The drugs causing haematological toxicity are mentioned in Table 1. Management Management varies from dose reduction to treatment for neutropenic sepsis. Patient who develop grade 4 toxicity ABSTRACT One of the characteristics that distinguish anticancer agents from other drugs is the frequency and severity of side effects at therapeutic doses. Most cytotoxic drugs target rapidly multiplying cells and the putative targets are the nucleic acids and their precursors, which are rapidly synthesised during cell division. Many solid tumours have a lower growth fraction than the normal bone marrow, gastro intestinal lining, reticuloendothelial system and gonads. Drugs affect these tissues in a dose dependant manner and there is individual susceptibility also. So toxicities are more frequently associated with these tissues. The side effects may be acute or chronic, self-limited, permanent, mild or potentially life threatening. Management of these side effects is of utmost importance because they affect the treatment, tolerability and overall quality of life. This paper gives an overview of different toxicities of anticancer drugs and its management.
Analysis of Antineoplastic Drugs: Clinical Pharmacology and Therapeutic Study
The current study depicts that it is observed the even the slight presence of easily oxidizable substance like thio-urea, ascorbic acid, hydrazine; alcohols etc. interfere in the estimation. In such case higher recovery is obtained because the compound reacts with the reagent. Therefore, the presence of such substances was avoided. Excipients like starch, calcium carbonate, sodium carbonate, cellulose, magnesium tri-silicate, tri-calcium phosphate and gum acacia if present in the pharmaceutical preparations do not interfere in the estimation. Background: Antineoplastic agents are a group of specialized drugs used primarily to treat cancer (the term "neoplastic" refers to cancer cells). The first antineoplastic agents used in the 1940s, were made from either synthetic chemicals or natural plants. Antineoplastic agents are classified by origin and by how they work to destroy cancer cells. Antineoplastic agents can be administered to patients alone or in combination with other antineoplastic drugs. They can also be given before, during or after a patient receives surgery radiation therapy. Antineoplastic agents travel the body and destroy cancer cells.Side effects are expected to occur when treated with these agents, and can include nausea, mouth sores, hair loss, and lowering of the blood counts. Many of the side effects associated with antineoplastic agents occur because chemotherapy treatment destroys the body's normal cells in addition to cancerous cells. Materials and Methods: An aliquot containing 5mg of the sample was taken in a l00mL stoppered conical flask and 5mL of 0.02NNCS reagent, prepared in hydrochloric acid and 5mL of 4N hydrochloric acid was added to it. The reaction mixture was shaken thoroughly and allowed to react for 15minutes at room temperature (25-300C). After the reaction is over 5mL of 5% potassium iodide was added to it. Contents were shaken thoroughly and allowed to react for a minute. The unconsumed NCS was determined iodometrically. A blank experiment was also run under identical conditions using all the reagents except the sample. Results: Methotrexate is a complex compound having six membered heterocyclic ring attached to substituted benzene ring which has got a side chain at para position attached to-NH2 group. The most probable reaction may be chlorination of the benzene ring at ortho position to substituted nitrogen atom. On this basis following reaction product may be postulated.Cytarabine is a derived pyrimidine base nucleus. One of the nitrogen is substituted five membered heterocyclic ring which contain a side chain having a primary hydroxy group. Etoposide is another complex molecule containing two benzene ring along with two five membered rings. One of the ring is highly substituted at ortho and meta position. The other benzene ring has got two five membered substituted cyclic rings. It has also got a glucopyranose ring attached through live membered cyclic ring. It becomes difficult to predict the reaction of this compound with NCS. The central benzene ring has got two active positions at para positions. Therefore chlorination may happen on these available positions. Doxorubicin hydrochloride has got four cyclic rings of which the main molecule is anthraquinone derivative. Conclusion: The current study depicts that it is observed the even the slight presence of easily oxidizable substance like thio-urea, ascorbic acid, hydrazine; alcohols etc. interfere in the estimation. In such case higher recovery is obtained because the compound reacts with the reagent. Therefore, the presence of such substances was avoided. Excipients like starch, calcium carbonate, sodium carbonate, cellulose, magnesium tri-silicate, tri-calcium phosphate and gum acacia if present in the pharmaceutical preparations do not interfere in the estimation.
2012
Captopril (D-3-mercapto-2-methylpropranoyl-L-proline) is an angiotensin converting enzyme inhibitor (ACEI), used in the treatment of hypertension and congestive heart failure. Angiotensin converting enzyme inhibitors have strong cytostatic properties on in-vitro cultures of many normal and neoplastic cells. 5 MATERIALS AND METHODS 1 millimolar (mM) Stock solution of captopril was prepared by dissolving 25mg of captopril oral tablet from Bristol-Myers Squibb company in 0.2 ml of dimethyl sulphoxide (DMSO) (USA-Sigma), and the volume was completed to 115.0483 ml by addition of phosphate buffered saline (PBS), filter using sterile millipore paper (0.22µm) and the PH was adjusted to (7.4) .Six concentrations were used in the study which were 7.5, 15, 22.5, 30.0, 37.5, 45.0 micromolar (μM). The cell lines were exposed to different concentrations of captopril solution, the periods of exposure of cell lines were measured at 24, 48, 72 and 96hrs in a microtitration plate under complete sterile conditions, and this was done in tri replicate for each concentration. Cancer cell lines Human Epidermoid Larynx Carcinoma (Hep-2) and Ahmed-Mohammed-Nahi-2003 (AMN-3) were obtained for biotechnology center/Al-Nahrain university/Baghdad. These cell lines were maintained in RPMI-1640 media with 10% (v/v) calf bovine serum and incubated at 37° C in a humidified atmosphere containing 5% C02 and 95% air. Cytotoxic assay The cytotoxic assay performed using the crystal violet was conducted as on 96-well plates. Tumor cells were seeded in 96-well microplates (Nunclon) at a concentration of 2x10 5 cell/well. Cancer cells were treated with each concentration of captopril solution in two fold serial
Antineoplastic Drugs : Treatment Principles and Toxicity
Veterinary World, 2011
The therapy of cancer has improved dramatically during the past half century. This improvement can be traced to a number of factors: a better understanding of cancer's cause and natural history, better technologies for early detection and diagnosis, improved control of primary tumors through surgery and radiation therapy and more effective drugs. The evolution of drug therapy for cancer has progressed rapidly from alkylating agents and antimetabolites to natural products, and most recently, molecular targeted drugs such as imatinib and gefitinib. As our understanding of the biology of cancer improves, new targets for therapy are being identified daily.
Cancer research, 1981
The cytotoxicities of a number of antineoplastic agents to oxygenated and hypoxic EMT6 mouse mammary tumor cells in culture were examined. Based on the relative sensitivities of cells under aerobic and hypoxic conditions, drugs were placed into three categories. Drugs that were preferentially toxic to cells under oxygenated conditions were classified as type 1 agents; this group includes bleomycin, procarbazine, streptonigrin, actinomycin D, and vincristine. Type 2 agents were those preferentially toxic to cells under hypoxic conditions. These include mitomycin C and Adriamycin. On the basis of other published reports, the glucose analogs, 5-thio-D-glucose and 2-deoxy-D-glucose, and the radiosensitizers, misonidazole and metronidazole, can also be placed in this category. Several antineoplastic agents showed no major preferential toxicity to cells under the conditions of oxygenation or hypoxia used in these experiments and were placed in a third class. This group (type 3) includes 1...