Authors:

Topics: Hodgkin Disease; Leukemia; Lymphoma; Triazines; Triethylenemelamine

PubMed: 14363905
DOI: No ID Found

Comparative Study

Authors: Catherine N Tchanque-Fossuo, Daniel B Eisen

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

Authors:

Topics: Triethylenemelamine

PubMed: 14935258
DOI: No ID Found

Authors: Marc A Beal, Matthew J Meier, Danielle P LeBlanc...

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

Authors: A A MARLOW, G R BARTLETT

X-radiation remains the treatment of choice in most cases of leukemia and lymphoma, but new agents are playing an increasing role in therapy. Radioactive phosphorus does not produce radiation sickness and results with it are comparable to those of x-ray therapy in chronic leukemia. Urethane and nitrogen mustard may produce remissions in patients with chronic leukemia who have become resistant to radiation. Triethylene melamine may be administered orally with nitrogen mustard-like effects and is undergoing further trial. Aminopterin, ACTH and cortisone often cause short remissions in acute leukemia. Urethane is the best treatment available for multiple myeloma. Polycythemia vera is well controlled by radioactive phosphorus combined with venesection. Nitrogen mustard is often effective and triethylene melamine shows promise in Hodgkin's disease. Antianemic substances such as iron and liver extract are of no value in the treatment of anemia caused by leukemia, lymphoma and myeloma.

Topics: Aminopterin; Chronic Disease; Hodgkin Disease; Humans; Leukemia; Lymphoma; Mechlorethamine; Multiple Myeloma; Neoplasms; Phlebotomy; Polycythemia; Triethylenemelamine; Urethane; X-Ray Therapy

PubMed: 13019601
DOI: No ID Found

Authors: M D'Incalci, E Erba, G Balconi...

The cytotoxicity of hexamethylmelamine (HMM) and its metabolites pentamethylmelamine (PMM), N,2,2,4,6-tetramethylmelamine (TMM) and hydroxymethylpentamethylmelamine (HMPMM) and of the alkylating agent triethylenemelamine (TEM) were studied on a cell line derived from a human ovarian cancer, by measuring [3H]TdR uptake. After 24 h of incubation all the tested compounds inhibited [3H]TdR uptake, but only at a concentration of 100 micrograms/ml. However, after 120 h incubation, concentrations of 0.1--10 micrograms/ml resulted in highly significant cytotoxicity. HMPMM and TEM were the most active and their effect was not reversed 72 h after their removal. In our in vitro system no metabolism of HMM was observed.

Topics: Altretamine; Cell Line; Cells; Female; Humans; Ovarian Neoplasms; Thymidine; Time Factors; Triazines

PubMed: 6770884
DOI: 10.1038/bjc.1980.106

Authors: A E Kusi-Appiah, T W Lowry, E M Darrow...

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

Authors: M BOCK, H JACKSON

Small doses of triethylenemelamine (TEM) had a selective action on the fertility of male rats. One dose (0.2 mg./kg., i.p.) produced effects ranging from subfertility to sterility during the next 3 weeks. In the fourth week sterility was the rule, but normal fertility was restored in the fifth week. A short course of the drug (5 daily doses, 0.2 mg./kg., i.p.) resulted in sterility lasting about 5 weeks, after which fertility was rapidly regained. Daily doses (0.05 mg./kg., i.p.) caused infertility in about a week which was maintained throughout treatment (7 weeks), and persisted for several weeks after the drug was discontinued. Sexual activity of infertile animals seemed normal and sperm production appeared to continue. Spermatozoa from infertile animals were able to reach and penetrate ova. The results suggest that TEM acts directly on the germinal epithelium. An attempt has been made to provide some explanation for these results and correlate them with the time required for spermatogenesis.

Topics: Animals; Fertility; Infertility; Male; Rats; Spermatogenesis; Spermatozoa; Triethylenemelamine

PubMed: 13413142
DOI: 10.1111/j.1476-5381.1957.tb01352.x

Authors: H E Luippold, P C Gooch, J G Brewen...

The cytogenetic effects of triethylenemelamine (TEM) were studied using five different mammalian tissues. Treatments of 0.1 and 0.2 mg/kg TEM on differentiating mouse spermatogonia and bone marrow cells showed no significant differences in the frequency of chromosomal aberrations produced in these two tissues. At higher doses, however, the sensitivites of the two tissues appear to be different. The frequency of aberrations varies with time after treatment, with the greatest amount occurring at the latter fixation times. Results of an experiment on primary spermatocytes indicated a correlation between the frequency of chromosome aberrations and DNA replication. Human peripheral leukocytes were utilized in an attempt to clarify the cell-stage specificity of TEM-induced chromosome aberrations. Cultures were treated with TEM prior to PHA stimulation (G0), as well as various time intervals after stimulation (late G,1 S, and G2). The most sensitive stages of the cell cycle to aberration induction were later G1 and S, with chromatid aberrations the predominant type. A very low yield of chromosome damage was observed with the G0 and G1 treated stages. The experiments described tend to support the view that TEM is most effective at inducing aberrations when an intervening round of DNA replication has occurred.

Topics: Animals; Bone Marrow; Bone Marrow Cells; Cells, Cultured; Chromosome Aberrations; Chromosomes; Dose-Response Relationship, Drug; Leukocytes; Male; Mice; Spermatogonia; Triethylenemelamine

PubMed: 565312
DOI: 10.1093/genetics/88.2.317

Authors: Francesco Marchetti, Gu Zhou, Danielle LeBlanc...

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