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British Medical Journal Jun 1955
Topics: Hodgkin Disease; Leukemia; Lymphoma; Triazines; Triethylenemelamine
PubMed: 14363905
DOI: No ID Found -
Communications Biology Aug 2020Transgenic rodent (TGR) models use bacterial reporter genes to quantify in vivo mutagenesis. Pairing TGR assays with next-generation sequencing (NGS) enables...
Transgenic rodent (TGR) models use bacterial reporter genes to quantify in vivo mutagenesis. Pairing TGR assays with next-generation sequencing (NGS) enables comprehensive mutation pattern analysis to inform mutational mechanisms. We used this approach to identify 2751 independent lacZ mutations in the bone marrow of MutaMouse animals exposed to four chemical mutagens: benzo[a]pyrene, N-ethyl-N-nitrosourea, procarbazine, and triethylenemelamine. We also collected published data for 706 lacZ mutations from eight additional environmental mutagens. We report that lacZ gene sequencing generates chemical-specific mutation signatures observed in human cancers with established environmental causes. For example, the mutation signature of benzo[a]pyrene, a carcinogen present in tobacco smoke, matched the signature associated with tobacco-induced lung cancers. Our results suggest that the analysis of chemically induced mutations in the lacZ gene shortly after exposure provides an effective approach to characterize human-relevant mechanisms of carcinogenesis and propose novel environmental causes of mutation signatures observed in human cancers.
Topics: Animals; Genes, Reporter; Genome, Human; High-Throughput Nucleotide Sequencing; Humans; Male; Mice, Transgenic; Mutation; Mutation Rate; Neoplasms; Transgenes; beta-Galactosidase
PubMed: 32796912
DOI: 10.1038/s42003-020-01174-y -
Dermatology Online Journal Nov 2018Cryotherapy is a commonly discussed method for treatment of basal cell carcinoma skin cancer. Some uncertainty remains about its efficacy relative to other modalities. (Comparative Study)
Comparative Study
BACKGROUND
Cryotherapy is a commonly discussed method for treatment of basal cell carcinoma skin cancer. Some uncertainty remains about its efficacy relative to other modalities.
OBJECTIVE
To determine the efficacy and adverse events profile of cryotherapy for the treatment of basal cell carcinoma compared to other therapeutic options or non-intervention.
METHODS
We systematically searched PubMed, OVID, Cochrane Library, EMBASE, CINHAL, and CANCERLIT databases for the following terms: "cryotherapy", AND "basal cell carcinoma", OR "cryosurgery" OR "cryoablation" up to April 2018. Two independent reviewers screened the results and extracted the data. Study endpoints included basal cell carcinoma recurrence, cosmetic outcome, and healing time. Study quality was assessed using the Jadad scale.
RESULTS
Six clinical studies met our inclusion criteria. The efficacy and safety of cryotherapy alone or with curettage in the treatment of primary superficial and nodular basal cell carcinoma was comparable to photodynamic therapy and surgery, respectively. Cryotherapy was inferior to radiation in terms of recurrence rate. Most patients had better cosmetic outcomes with photodynamic therapy and surgery compared to cryotherapy alone, and cryotherapy with curettage.
CONCLUSION
Current available data suggests equivalent efficacy of cryotherapy alone compared to photodynamic therapy or surgery, but inferior to radiotherapy. More studies are necessary to draw definitive conclusions.
Topics: Carcinoma, Basal Cell; Cryosurgery; Dermatologic Surgical Procedures; Humans; Neoplasm Recurrence, Local; Photochemotherapy; Skin Neoplasms; Triethylenemelamine; Wound Healing
PubMed: 30695972
DOI: No ID Found -
Archives of Toxicology Mar 2021The Organisation for Economic Co-Operation and Development Test Guideline 488 (TG 488) uses transgenic rodent models to generate in vivo mutagenesis data for regulatory...
The Organisation for Economic Co-Operation and Development Test Guideline 488 (TG 488) uses transgenic rodent models to generate in vivo mutagenesis data for regulatory submission. The recommended design in TG 488, 28 consecutive daily exposures with tissue sampling three days later (28 + 3d), is optimized for rapidly proliferating tissues such as bone marrow (BM). A sampling time of 28 days (28 + 28d) is considered more appropriate for slowly proliferating tissues (e.g., liver) and male germ cells. We evaluated the impact of the sampling time on mutant frequencies (MF) in the BM of MutaMouse males exposed for 28 days to benzo[a]pyrene (BaP), procarbazine (PRC), isopropyl methanesulfonate (iPMS), or triethylenemelamine (TEM) in dose-response studies. BM samples were collected + 3d, + 28d, + 42d or + 70d post exposure and MF quantified using the lacZ assay. All chemicals significantly increased MF with maximum fold increases at 28 + 3d of 162.9, 6.6, 4.7 and 2.8 for BaP, PRC, iPMS and TEM, respectively. MF were relatively stable over the time period investigated, although they were significantly increased only at 28 + 3d and 28 + 28d for TEM. Benchmark dose (BMD) modelling generated overlapping BMD confidence intervals among the four sampling times for each chemical. These results demonstrate that the sampling time does not affect the detection of mutations for strong mutagens. However, for mutagens that produce small increases in MF, sampling times greater than 28 days may produce false-negative results. Thus, the 28 + 28d protocol represents a unifying protocol for simultaneously assessing mutations in rapidly and slowly proliferating somatic tissues and male germ cells.
Topics: Animals; Dose-Response Relationship, Drug; Germ Cells; Male; Mice; Mice, Transgenic; Mutagenesis; Mutagenicity Tests; Mutagens; Mutation; Time Factors
PubMed: 33506374
DOI: 10.1007/s00204-021-02977-6 -
British Journal of Cancer Sep 1958
Topics: Hodgkin Disease; Mechlorethamine; Nitrogen Mustard Compounds; Triethylenemelamine
PubMed: 13596499
DOI: 10.1038/bjc.1958.54 -
Lab on a Chip Aug 2015The dose-dependent bioactivity of small molecules on cells is a crucial factor in drug discovery and personalized medicine. Although small-molecule microarrays are a...
The dose-dependent bioactivity of small molecules on cells is a crucial factor in drug discovery and personalized medicine. Although small-molecule microarrays are a promising platform for miniaturized screening, it has been a challenge to use them to obtain quantitative dose-response curves in vitro, especially for lipophilic compounds. Here we establish a small-molecule microarray assay capable of controlling the dosage of small lipophilic molecules delivered to cells by varying the sub-cellular volumes of surface supported lipid micro- and nanostructure arrays fabricated with nanointaglio. Features with sub-cellular lateral dimensions were found necessary to obtain normal cell adhesion with HeLa cells. The volumes of the lipophilic drug-containing nanostructures were determined using a fluorescence microscope calibrated by atomic-force microscopy. We used the surface supported lipid volume information to obtain EC-50 values for the response of HeLa cells to three FDA-approved lipophilic anticancer drugs, docetaxel, imiquimod and triethylenemelamine, which were found to be significantly different from neat lipid controls. No significant toxicity was observed on the control cells surrounding the drug/lipid patterns, indicating lack of interference or leakage from the arrays. Comparison of the microarray data to dose-response curves for the same drugs delivered liposomally from solution revealed quantitative differences in the efficacy values, which we explain in terms of cell-adhesion playing a more important role in the surface-based assay. The assay should be scalable to a density of at least 10,000 dose response curves on the area of a standard microtiter plate.
Topics: Aminoquinolines; Antineoplastic Agents; Cell Adhesion; Cell Survival; Docetaxel; Drug Discovery; HeLa Cells; Humans; Imiquimod; Liposomes; Microarray Analysis; Microscopy, Atomic Force; Microscopy, Fluorescence; Nanostructures; Precision Medicine; Taxoids; Triethylenemelamine
PubMed: 26167949
DOI: 10.1039/c5lc00478k -
Canadian Medical Association Journal Mar 1964Chemotherapy of solid tumours is considered with respect to cell vulnerability, toxicity, tissue penetrability, tumour disruption and anatomical location. Chemotherapy...
Chemotherapy of solid tumours is considered with respect to cell vulnerability, toxicity, tissue penetrability, tumour disruption and anatomical location. Chemotherapy to date has dealt primarily with the first two factors. Even when the cell is vulnerable to the agent used and host toxicity can be controlled, the other factors can lead to treatment failures. It is suggested that combinations of cytotoxic agents may be of more value than single agents. Timing and dosage are also considered. It is recommended that terminal cases and extremely toxic patients not be submitted to chemotherapy. In 78 patients with bronchogenic carcinoma, to whom nicotinic acid was given as a possible aid to tissue penetrability by nitrogen mustard, there was some indication that further similar studies might be of some value. Specific cases are summarized to illustrate the importance of various factors in the treatment of individual patients.
Topics: Breast Neoplasms; Cyclophosphamide; Fluorouracil; Humans; Mechlorethamine; Neoplasms; Thiotepa; Toxicology; Triethylenemelamine; Vinblastine
PubMed: 14127380
DOI: No ID Found -
Environmental Health Perspectives Apr 1978Previously we reported negative terata and c-mitosis synergism of FireMaster (polybrominated biphenyls) with colchicine in subacutely treated rats. Now we report absence...
Previously we reported negative terata and c-mitosis synergism of FireMaster (polybrominated biphenyls) with colchicine in subacutely treated rats. Now we report absence of chromosome aberrations from FireMaster and absence of c-mitosis synergism of FireMaster and colchicine in male mice. For the study of chromosome aberrations groups of three mice received 0, 50, or 500 mg/kg FireMaster or 4.5 mg/kg triethylenemelamine (TEM) dissolved in dimethyl sulfoxide through a single stomach gavage administration. Five hours before killing the animals were injected with 5 mg colchicine/kg. Groups of 3 mice from each treatment killed 12, 24, and 48 hr after treatment. From the bone marrow of each of 36 mice 100 metaphases were scored for gaps, chromatid and chromosome breaks, rearrangements and pulverized chromosomes. Only TEM induced chromosome damage. For detection of synergism between FireMaster and colchicine, slides prepared for chromosome analysis were also scored for metaphase and mitotic indeces. Control mice for detection of synergism were treated as for the chromosome study but were not injected with colchicine. Approximately 1000 cells were scored from each of 72 animals for determination of metaphase and mitotic indeces. FireMaster did not show c-mitosis synergism with colchicine in mice. Treatment with FireMaster did not cause visually recognizable toxicity.
Topics: Abnormalities, Drug-Induced; Animals; Biphenyl Compounds; Bone Marrow Cells; Chromosome Aberrations; Colchicine; Drug Synergism; Female; Flame Retardants; Male; Metaphase; Mice; Mitosis; Mitotic Index; Polybrominated Biphenyls; Pregnancy; Rats
PubMed: 209964
DOI: 10.1289/ehp.7823129 -
Trisethylene-imino-s-triazine (triethylene melamine or TEM) in the treatment of neoplastic diseases.California Medicine Jul 1951Trisethylene-imino-s-triazine (triethylene melamine or TEM) produced minimal effects in inhibiting transplantable lymphoma and mammary adenocarcinoma in mice. In strain...
Trisethylene-imino-s-triazine (triethylene melamine or TEM) produced minimal effects in inhibiting transplantable lymphoma and mammary adenocarcinoma in mice. In strain A mice, injection of the compound induced pulmonary tumors.TEM was tried on 32 patients with neoplastic disease, including nine patients with Hodgkin's disease and five with lymphosarcoma and lymphatic leukemia. The therapeutic and toxic effects were similar to those observed with nitrogen mustard (HN2). Satisfactory remissions of up to three months were observed in Hodgkin's disease and lymphosarcoma following parenteral administration of TEM. It is the authors' impression that the remissions obtained with TEM were not as complete and did not last as long as those obtained with HN2.TEM is effective by the oral route as well as parenterally, and produces much less emetic reaction than HN2. On the other hand, the chemotherapeutic range is narrower than that of HN2. Patients who do not respond to HN2 show no response to TEM.TEM is a drug of some clinical usefulness in the same conditions and with the same general limitations and toxic effects as HN2. The ease of administration of TEM increases its hazards, and close clinical and hematologic observations are essential on patients receiving the agent.
Topics: Animals; Hodgkin Disease; Humans; Lung Neoplasms; Lymphoma; Mechlorethamine; Mice; Neoplasms; Nitrogen Mustard Compounds; Triazines; Triethylenemelamine
PubMed: 14848718
DOI: No ID Found -
Immunology Jan 1964Mice were injected with T.A.B. vaccine and, 2 days later, with various doses of different compounds. The relation between dose of compound, mortality and antibody...
Mice were injected with T.A.B. vaccine and, 2 days later, with various doses of different compounds. The relation between dose of compound, mortality and antibody production was studied, and therapeutic indices were calculated for a number of compounds. The most effective agent in suppressing antibody production at relatively non-toxic doses was cyclophosphamide, with next amethopterin (the effect of which was, however, inexplicably erratic), 6-thioguanine and 6-mercaptopurine, in that order. Vincaleukoblastine, triethylene melamine, triethylenethiophosphoramide, mannomustine and 5-fluorouracil were less effective. Compounds of a miscellaneous group (boric acid, caffeine, sodium nitrite, bacitracin, neomycin and polymyxin `B') were studied in the same way: they had no effect on antibody production, even in lethal doses.
Topics: Allergy and Immunology; Antibody Formation; Antineoplastic Agents; Autoimmune Diseases; Cyclophosphamide; Fluorouracil; Immunity; Mannomustine; Mercaptopurine; Methotrexate; Mice; Mortality; Research; Thioguanine; Toxicology; Transplantation; Triethylenemelamine; Typhoid-Paratyphoid Vaccines; Vinblastine
PubMed: 14113077
DOI: No ID Found