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Skinmed 2016
Topics: Antineoplastic Agents, Alkylating; Humans; Mechlorethamine; Mycosis Fungoides
PubMed: 27319956
DOI: No ID Found -
Clinical Lymphoma, Myeloma & Leukemia Aug 2022Mycosis fungoides (MF), the most common subtype of Cutaneous T-cell lymphomas, is caused by malignant T-cell proliferations in the skin that can invade blood, lymph...
BACKGROUND
Mycosis fungoides (MF), the most common subtype of Cutaneous T-cell lymphomas, is caused by malignant T-cell proliferations in the skin that can invade blood, lymph nodes, or viscera. Currently, data on efficacy of maintenance therapies in MF are lacking. We developed a unique protocol to use chlormethine/mechlorethamine 0.016% gel formulation as maintenance regimen for MF patients in remission.
PURPOSE
To determine progression-free survival and efficacy of chlormethine/mechlorethamine as maintenance and active treatment regimens for MF.
MATERIALS AND METHODS
A retrospective review of MF patients seen at Thomas Jefferson University from 2012 to 2020 was conducted. Patients of all stages treated with chlormethine/mechlorethamine as maintenance or active treatment with 2 consecutive mSWATs (modified Severity Weighted Assessment Tool) documented were included. Treatment outcomes were assessed by change in mSWAT and progression-free survival. Dermatology Life Quality Index surveys before and after treatment were analyzed.
RESULTS
Of 186 MF patients, 44 met inclusion criteria. Patients on maintenance therapy had a 65.22% progression-free survival rate with median time to progression of 29.45 months. By-time analysis for responders on active and maintenance treatment showed an increased response over time. Peak responses were seen at last mSWAT recorded. Both cohorts experienced improved quality-of-life scores from initiation to discontinuation of chlormethine/mechlorethamine.
CONCLUSION
Patients on maintenance and active chlormethine/mechlorethamine treatment regimens demonstrated improvement in mSWAT and quality-of-life. Chlormethine/mechlorethamine treatment showed progression-free survival for a median of 29.45 months, indicating this therapy may be an effective maintenance regimen.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mechlorethamine; Mycosis Fungoides; Retrospective Studies; Skin Neoplasms
PubMed: 35393251
DOI: 10.1016/j.clml.2022.02.002 -
International Journal of Dermatology Apr 1984
Review
Topics: Administration, Topical; Dermatitis, Contact; Humans; Mechlorethamine; Mycosis Fungoides; Skin Neoplasms
PubMed: 6373639
DOI: 10.1111/j.1365-4362.1984.tb04507.x -
Annals of Internal Medicine Jun 1981
Topics: Drug Hypersensitivity; Female; Humans; Mechlorethamine; Middle Aged
PubMed: 7235433
DOI: 10.7326/0003-4819-94-6-823_2 -
Drug and Chemical Toxicology Jul 2020Mechlorethamine (HN2) is an alkylating agent and sulfur mustard mimetic. Topical exposure to HN2 is associated with tissue blistering. Previous work in our laboratory...
Mechlorethamine (HN2) is an alkylating agent and sulfur mustard mimetic. Topical exposure to HN2 is associated with tissue blistering. Previous work in our laboratory has shown that ebselen (EB-1) possesses anti-vesicant, anti-inflammatory, anti-bacterial, anti-fungal, and cytoprotective properties, both and . We recently reported that ebselen oxide (EB-2), an analog of EB-1 with a tetravalent selenium atom, also possesses anti-bacterial and anti-fungal activity and confers cytoprotection against HN2 . The purpose of the present study was to determine the vesicant countermeasure potential of EB-2 using the mouse ear vesicant model (MEVM). Compared to control ears, mouse ears exposed to a single dose of HN2 (0.500 µmol/ear) showed an increase in wet weights, ear thickness, hyperplasia, vesication, and inflammatory cell infiltration after 24 h. Fluorescence microscopy of terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL)-stained sections showed that the occurrence of apoptosis extended from the epidermis of the HN2-treated side, all the way to the contralateral epidermis. In contrast, HN2-exposed ears treated topically with EB-2 at a test dose of 0.250 mg/ear showed a significant decrease in wet weight (12% less vs. HN2 alone), morphometric thickness (13% less vs. HN2 alone), and vesication. In addition, TUNEL staining revealed that HN2 ears treated with EB-2 (0.250 mg/ear) showed a decrease in apoptosis as compared to the HN2 group. EB-2 also reduced the abundance of matrix metalloproteinase-9 (MMP-9) in ear tissues exposed to HN2. Taken together, our study demonstrates that EB-2 is an efficacious countermeasure to HN2.
Topics: Alkylating Agents; Animals; Apoptosis; Azoles; Cytoprotection; Ear; Irritants; Isoindoles; Mechlorethamine; Mice; Organoselenium Compounds; Skin
PubMed: 30257109
DOI: 10.1080/01480545.2018.1488858 -
Cells Jul 2023Sulfur mustard (SM) and nitrogen mustard (NM) are vesicant agents that cause skin injury and blistering through complicated cellular events, involving DNA damage, free...
Sulfur mustard (SM) and nitrogen mustard (NM) are vesicant agents that cause skin injury and blistering through complicated cellular events, involving DNA damage, free radical formation, and lipid peroxidation. The development of therapeutic approaches targeting the multi-cellular process of tissue injury repair can potentially provide effective countermeasures to combat vesicant-induced dermal lesions. MG53 is a vital component of cell membrane repair. Previous studies have demonstrated that topical application of recombinant human MG53 (rhMG53) protein has the potential to promote wound healing. In this study, we further investigate the role of MG53 in NM-induced skin injury. Compared with mice, mice are more susceptible to NM-induced dermal injuries, whereas mice with sustained elevation of MG53 in circulation are resistant to dermal exposure of NM. Exposure of keratinocytes and human follicle stem cells to NM causes elevation of oxidative stress and intracellular aggregation of MG53, thus compromising MG53's intrinsic cell membrane repair function. Topical rhMG53 application mitigates NM-induced dermal injury in mice. Histologic examination reveals the therapeutic benefits of rhMG53 are associated with the preservation of epidermal integrity and hair follicle structure in mice with dermal NM exposure. Overall, these findings identify MG53 as a potential therapeutic agent to mitigate vesicant-induced skin injuries.
Topics: Mice; Humans; Animals; Mechlorethamine; Irritants; Keratinocytes; Wound Healing; Membrane Proteins
PubMed: 37508578
DOI: 10.3390/cells12141915 -
Cancer Dec 1983The treatment of skin disease with topical mechlorethamine has been restricted because of the frequent development of contact dermatitis. A series of 43 patients with...
The treatment of skin disease with topical mechlorethamine has been restricted because of the frequent development of contact dermatitis. A series of 43 patients with mycosis fungoides in Stages 1A (17), IB (22), II (2), and III (2) were treated with an ointment-based mechlorethamine, prepared by an anhydrous method. Complete clearing occurred in 26 patients over a 42-month evaluation period. The incidence of contact dermatitis was very low. Only 1 of 31 patients exposed to mechlorethamine for the first time, and only 3 of 12 patients with a history of previous hypersensitivity to mechlorethamine, developed contact dermatitis to the ointment-based mechlorethamine.
Topics: Administration, Topical; Dermatitis, Contact; Evaluation Studies as Topic; Humans; Mechlorethamine; Mycosis Fungoides; Ointments
PubMed: 6640491
DOI: 10.1002/1097-0142(19831215)52:12<2214::aid-cncr2820521207>3.0.co;2-h -
The British Journal of Dermatology Nov 1977Patients with limited skin involvement by mycosis fungoides were treated with daily topical mechlorethamine. Seven of thirteen patients had a complete remission of...
Patients with limited skin involvement by mycosis fungoides were treated with daily topical mechlorethamine. Seven of thirteen patients had a complete remission of diseases. Six of these seven experienced a contact dermatitis and four underwent a successful topical desensitization programme. The possible beneficial therapeutic effects of developing a contact allergy are discussed.
Topics: Administration, Topical; Dermatitis, Contact; Desensitization, Immunologic; Female; Humans; Male; Mechlorethamine; Middle Aged; Mycosis Fungoides; Skin Neoplasms
PubMed: 588466
DOI: 10.1111/j.1365-2133.1977.tb14133.x -
JAMA Feb 1968
Clinical Trial Comparative Study Randomized Controlled Trial
Topics: Chlorambucil; Clinical Trials as Topic; Cyclophosphamide; Dosage Forms; Follow-Up Studies; Hodgkin Disease; Humans; Injections, Intravenous; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mechlorethamine
PubMed: 4865234
DOI: No ID Found -
Biochemistry Jan 1995The dG-to-dG, DNA-DNA interstrand cross-link at the duplex sequence 5'-d(GNC) formed by the antitumor drug mechlorethamine (bis(2-chloroethyl)methylamine) was studied...
The dG-to-dG, DNA-DNA interstrand cross-link at the duplex sequence 5'-d(GNC) formed by the antitumor drug mechlorethamine (bis(2-chloroethyl)methylamine) was studied both theoretically and experimentally. Computer models of cross-linked DNA were energy minimized using molecular mechanics. The energy minimized structures possessed local distortion of the DNA helix, especially propeller twisting and buckling, caused by the tether length being too small to bridge the spacing of N7 atoms of dG at the sequence 5'-d(GNC) in B DNA. Overwinding of 2-6 degrees was present at each of the two dinucleotide steps spanned by the cross-link. The predicted structural changes were compatible with the possibility that this cross-link would introduce a static bend into the DNA double helix axis. An experimental study provided evidence for this induced bending of the helix axis in interstrand cross-linked samples. DNAs containing multiple mechlorethamine-induced interstrand cross-links exhibited anomalously low electrophoretic mobility in polyacrylamide gels when the lesions were separated by one or two turns. From the degree of gel retardation, the cross-linked DNAs were estimated to be bent by 12.4-16.8 degrees per lesion; estimation of the extent to which this bend was induced by the lesion was complicated by a preexisting bend in the non-cross-linked DNAs used. The data did not allow distinction of a static from an anisotropic dynamic bend; "universal" and "hinge" joints were excluded. Anomalous mobility was maximal when the lesion spacing was 21 bp, suggesting a helical repeat of 10.5 bp per turn.
Topics: Base Sequence; Cross-Linking Reagents; DNA; Electrophoresis, Polyacrylamide Gel; Mechlorethamine; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; Oligodeoxyribonucleotides
PubMed: 7827092
DOI: 10.1021/bi00004a039