chromomycin-a3 and Neoplasms

Overactivation in Ras signaling has been under intensive study as the molecular basis for development of cancer. Such overactivation can occur in the presence or absence of mutations in Ras gene resulting in activation of a series of down-stream effectors such as transcription factors. Different studies have shown the activation of Ras down-stream effectors in non-Hodgkin lymphoma (NHL) although mutations in Ras are not prevalent in this malignancy. Since overactivation in Ras signaling also increases permissiveness of cancer cells to infection by oncolytic versions of herpes simplex virus (e.g. R3616), we were interested in evaluating the value of transcription factors down-stream of Ras as molecular indicators for permissiveness to herpes therapy. In order to accomplish this, and also to assess the permissiveness of lymphoma cells to infection with R3616, we used NHL cell lines Daudi, Jurkat, NC37, Raji, Ramos and ST486. Once the levels of phosphorylation (activation) of extracellular-signal regulated kinase (ERK, a Ras effector pathway) and its down-stream transcription factor ELK were evaluated, Raji and NC37 showed a significant increase in the phosphorylation levels of both molecules while ATF2 (another transcription factor down-stream of p38-kinase pathway) seemed to be activated in all studied cells. Raji and NC37 cells were also most permissive cells to infection with R3616 while their permissiveness was decreased upon treatment of cells with an inhibitor of ELK-DNA binding portraying ERK/ELK as a suitable predictive indicator for selection of cancer cells with increased sensitivity to R3616. This study, therefore, for the first time documents permissiveness of lymphoma cells to oncolytic herpes viruses and introduces ELK as a suitable factor for predicting tumor susceptibility to these novel anticancer agents.

Topics: Antibiotics, Antineoplastic; Cell Line, Tumor; Chromomycin A3; ets-Domain Protein Elk-1; Herpesviridae; Humans; Molecular Structure; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; ras Proteins; Signal Transduction; Transcription Factors

The total variation of chromosome peak positions, in bivariate distributions of Hoechst 33258 and chromomycin A3 fluorescence of 19 healthy individuals, was compared with the experimental variation, determined from 23 bivariate distributions of chromosomes prepared separately from a single cell lineage. The experimental variation in Hoechst and chromomycin fluorescence and the relative chromosomal DNA content were determined from experiments performed over several days. The additional variance contributed by time was the same as the daily variance. The accuracy by which the relative chromosomal DNA content can be calculated from bivariate peak positions was investigated. A least squares method was used to fit the distributions of relative DNA content, obtained, respectively, from mono- and bivariate flow analyses of chromosomes from the same cell lineage. In general the DNA contents match quite well, but for a few chromosomes a difference was found, statistically discernible at the 5% level. The average relative chromosomal DNA content of the chromosomes from the 19 normal individuals, calculated from bivariate peak positions, showed a linear relation with the estimates published by other investigators.

Topics: Bisbenzimidazole; Cells, Cultured; Chromomycin A3; Chromosomes, Human; Citrates; Citric Acid; DNA; Fibroblasts; Flow Cytometry; Fluorescent Dyes; Humans; Karyotyping; Least-Squares Analysis; Neoplasms

Vanadium is a trace element widely distributed in nature. It interferes with a variety of enzyme systems and is also reported to increase DNA-synthesis and in vitro clonal growth of human and mouse fibroblasts. The purpose of the present study was to determine the effect of vanadium salts on the in vitro growth of fresh human tumor specimens. Various concentrations of ammonium metavanadate (AMV), vanadyl sulfate trihydrate (VST) and ortho sodium vanadate (OSV) were tested in a human tumor cloning assay (HTCA). Thirty-four evaluable specimens were tested at concentrations of less than or equal to 10(-10) M of one or more vanadium salts. At this concentration, colony formation was increased by greater than or equal to 150% as compared to control at one or more concentrations in 16 specimens (47%). Twelve evaluable specimens were tested against various concentrations greater than 10(-10) M. Colony formation was inhibited by greater than or equal to 50% of the control at one or more concentrations in all specimens. In further experiments we performed a head-to-head comparison of OSV (10(-3)M) and our standard positive control for cell kill (chromomycin A3, 100 micrograms/ml) in 34 specimens. OSV led to a comparable or better cell kill in 28 tumors (82%). We conclude that vanadium salts at low concentrations (less than or equal to 10(-10)M) can stimulate in vitro colony formation from human tumors. At higher concentrations (greater than 10(-10)M) tumor colony formation is inhibited. OSV might be useful as a very inexpensive positive control in the HTCA. In addition, the value of vanadium salts as antitumor agents should be further investigated in vivo.

Topics: Cell Division; Cell Survival; Chromomycin A3; Clone Cells; Dose-Response Relationship, Drug; Humans; Neoplasms; Neoplastic Stem Cells; Vanadium

Topics: Adolescent; Antineoplastic Agents; Bone Neoplasms; Chromomycin A3; Drug Therapy; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Neoplasms; Sarcoma

Topics: Anti-Bacterial Agents; Ascites; Carcinoma, Hepatocellular; Cell Nucleus; Chromomycin A3; Dactinomycin; Liver Neoplasms; Mechlorethamine; Metabolism; Neoplasms; Neoplasms, Experimental; Pharmacology; Rats; Research; RNA; RNA, Neoplasm; RNA, Nuclear

Topics: Anti-Bacterial Agents; Chromomycin A3; Cyclophosphamide; Esophageal Neoplasms; Geriatrics; Laryngeal Neoplasms; Laryngectomy; Maxillary Neoplasms; Mesenchymoma; Neoplasm Metastasis; Neoplasms; Otolaryngology; Surgical Procedures, Operative; Tongue Neoplasms; Tonsillar Neoplasms

Topics: Anti-Bacterial Agents; Cell Biology; Chromomycin A3; Metabolism; Neoplasms; Neoplasms, Experimental; Nucleic Acids; Pharmacology

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Antineoplastic Agents; Chromomycin A3; Dermatologic Agents; Neoplasm Transplantation; Neoplasms