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Archives of Dermatology Nov 1975Further attempts to induce immunological tolerance in 29 psoriatic patients treated topically with mechlorethamine hydrochloride have not been successful using the... (Comparative Study)
Comparative Study
Further attempts to induce immunological tolerance in 29 psoriatic patients treated topically with mechlorethamine hydrochloride have not been successful using the intravenous route. The rate of sensitization achieved (65%) is not substantially different from the rate for those patients who had no attempt to induce tolerance (55.5%).
Topics: Adult; Dermatitis, Contact; Humans; Hypersensitivity; Immune Tolerance; Male; Mechlorethamine; Psoriasis
PubMed: 1200651
DOI: 10.1001/archderm.111.11.1438 -
The Journal of Investigative... Oct 2003Alopecia areata is regarded as a tissue-restricted autoimmune disease of hair follicles in which follicular activity is arrested because of the continued activity of... (Review)
Review
Alopecia areata is regarded as a tissue-restricted autoimmune disease of hair follicles in which follicular activity is arrested because of the continued activity of lymphocytic infiltrates. Actual loss of hair follicles does not occur, even in hairless lesions. A variety of immunomodulating therapies, including contact sensitizers and immunomodulators, are part of the usual armamentarium for this disorder. None of these treatments have been consistent in their efficacy, and many have untoward side effects. Nevertheless, their uses in valid animal models provide a tool to dissect out molecular mechanisms of therapeutic effects. For several decades, both mechlorethamine (for the treatment of cutaneous T cell lymphoma) and anthralin (for the treatment of psoriasis) have been used successfully. When these therapies were tested in rat and mouse alopecia areata models, we found anthralin and mechlorethamine to be the most effective topical modalities, respectively. The underlying cellular mechanisms may act through targeting infiltrative lymphocytes, and the molecular mechanisms may involve specific cytokine expression changes. These visible, accessible, and unilaterally treated animal model systems are ideal for studying novel alopecia areata therapies, particularly in terms of their in vivo molecular mechanisms of action.
Topics: Alopecia Areata; Animals; Anthralin; Disease Models, Animal; Mechlorethamine; Rodentia
PubMed: 14582676
DOI: 10.1046/j.1087-0024.2003.00812.x -
Pharmacological Reports : PR 2011Nitrogranulogen (NTG) may modify the character of inflammatory reactions. These modifications are a result of cytotoxic and mutagenic effects. NTG has high affinity to...
Nitrogranulogen (NTG) may modify the character of inflammatory reactions. These modifications are a result of cytotoxic and mutagenic effects. NTG has high affinity to DNA and causes disorders in the synthesis of acute phase proteins (e.g., haptoglobin, transferrin, fibrinogen, and complement protein C3). Our previous studies have shown that small doses of NTG can enhance immunological defense reactions in the organism. The aim of the current studies was to determine how different NTG doses cause changes in the values of biochemical parameters in pleuritis-induced rats. The animals were randomized into five groups: Group I - control group; Group II - IP (induced pleuritis) group; Group III - NTG5 group; Group IV - NTG50 group; Group V - NTG600 group. Blood was collected from all groups of animals at 24, 48, and 72 h after the initiation of the carrageenin-induced inflammatory reaction. These investigations revealed that a dose of 5 μg NTG/kg b.w. (body weight) can change the character of the inflammation. Our studies also show that a dose of 600 μg NTG/kg b.w. causes a rapid decrease in the level of C3 at the 72 h of the experiment (after 3 applications every 24 h), which indicates a cytotoxic action of such a large NTG dose. NTG used at doses of 50 and 600 μg/kg b.w. causes the opposite metabolism of albumins and other serum proteins. Our studies show that the different doses of NTG have distinct effects on the inflammatory reaction.
Topics: Acute-Phase Proteins; Alkylating Agents; Animals; Carrageenan; Complement C3; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Mechlorethamine; Pleurisy; Rats; Rats, Inbred BUF; Time Factors
PubMed: 21602606
DOI: 10.1016/s1734-1140(11)70517-5 -
Dermatologic Therapy Sep 2022Gel formulation of chlormethine (CG) has gained a preeminent role among therapies available for mycosis fungoides (MF). To evaluate the frequency of use of CG for MF... (Review)
Review
Gel formulation of chlormethine (CG) has gained a preeminent role among therapies available for mycosis fungoides (MF). To evaluate the frequency of use of CG for MF treatment and to determine the limits and potentialities of CG in a real-world setting. A systematic review of articles published prior to October 2021 was performed. Articles were included in the review if a full-text English version was available. MEDLINE (PubMed), Scopus, and Web of Science were each queried from their date of inception with the following terms: "mechlorethamine gel", "chlormethine gel", and "mycosis fungoides". The reference lists of the studies retrieved were searched manually. Moreover, this study included all consecutive patients with different stages of MF (from IA to IIB) who started treatment with CG gel between July 2020 and May 2021. Data of the literature were compared to our single-center real-life experience. Of the surveyed literature, 11 publications were included in the final analysis describing a total of 548 patients with MF. Eleven patients with a median (standard deviation) age of 66 years (15.1) were enrolled and followed up, receiving CG (0.02% chlormethine HCl). Response to treatment resulted higher (90.1%) in our study population than in other real-world experiences published in literature. This systematic review supports the role of CG for MF treatment, showing its limits and potentialities. Our single-center real-life experience revealed an elevated percentage of clinical response with high safety and tolerance, demonstrating its versatile use with dose and application rate adaptability.
Topics: Aged; Gels; Humans; Mechlorethamine; Mycosis Fungoides; Skin Neoplasms
PubMed: 35778940
DOI: 10.1111/dth.15683 -
Archives of Dermatology Nov 1970
Clinical Trial
Topics: Adult; Drug Hypersensitivity; Edema; Erythema; Female; Humans; Lactose; Male; Mechlorethamine; Middle Aged; Pigmentation Disorders; Pruritus; Psoriasis; Solutions; Time Factors
PubMed: 5474112
DOI: No ID Found -
Dalton Transactions (Cambridge, England... Sep 2011The reaction of K(2)PtCl(4) with the alkylating agent mechlorethamine hydrochloride, at a molar ratio of 1:2, results in the formation of...
Insight into hydrolytic reaction of N-acetylated L-histidylglycine dipeptide with novel mechlorethamine platinum(II) complex. NMR and DFT study of the hydrolytic reaction.
The reaction of K(2)PtCl(4) with the alkylating agent mechlorethamine hydrochloride, at a molar ratio of 1:2, results in the formation of 2-chloro-N-(2-chloroethyl)-N-methylethylammonium-tetrachloridoplatinate(II) complex. The hydrolytic activity of the novel Pt(II) complex was tested in the reaction with N-acetylated L-histidylglycine dipeptide at a molar ratio 1:1. It was shown that the hydrolytic reaction, performed at 60 °C in acidic medium, leads to the regioselective cleavage of the amide bond involving the carboxylic group of histidine. Density functional theory was used to explore the structures of the proposed participants in the hydrolytic reaction.
Topics: Acetylation; Alkylating Agents; Dipeptides; Hydrolysis; Magnetic Resonance Spectroscopy; Mechlorethamine; Models, Molecular; Organoplatinum Compounds; Quantum Theory
PubMed: 21837317
DOI: 10.1039/c1dt10593k -
Journal Der Deutschen Dermatologischen... May 2022In Europe chlormethine gel is licensed for the management of patients with mycosis fungoides of all stages. However, the optimal regimen regarding frequency and dosing... (Review)
Review
BACKGROUND
In Europe chlormethine gel is licensed for the management of patients with mycosis fungoides of all stages. However, the optimal regimen regarding frequency and dosing as well as combination and maintenance therapy is not well established.
METHODS
Ten experts experienced in research and management of cutaneous T-cell lymphomas from Germany, Austria, and Switzerland (DACH region) were asked in written form to report on indication for chlormethine gel, frequency of use, monitoring, concomitant therapies, adverse effects, combination therapies in later stages of the disease, maintenance therapy, and adherence to this therapy for mycosis fungoides. The structured answers were discussed in a consensus conference and recommendations were developed.
RESULTS
Essential for therapy with chlormethine gel is an individualized and symptom-oriented management. Because of the lack of systemic resorption of topically administered chlormethine gel, systemic adverse events are unlikely. An allergic or irritative-toxic contact dermatitis is common but manageable with adaptation of the regimen, interruption of administration, and symptom-specific supportive measurements. A step-up initial approach with application of chlormethine gel every other day is associated with a better tolerability, especially if it is alternated with topical corticosteroids.
CONCLUSIONS
The use of chlormethine gel in the management of mycosis fungoides is often limited by a concomitant contact dermatitis. An adequate therapeutic regimen and the management of adverse effects can preclude an unnecessary withdrawal of therapy so that more patients can benefit from this treatment option.
Topics: Austria; Cyclohexylamines; Dermatitis, Contact; Humans; Mechlorethamine; Mycosis Fungoides; Skin Neoplasms; Switzerland
PubMed: 35429108
DOI: 10.1111/ddg.14688 -
Advances in Therapy Sep 2022Mycosis fungoides (MF) is a rare disease and is the most common form of cutaneous T cell lymphoma. Topical chlormethine (CL) gel is the first cytotoxic chemotherapy gel... (Review)
Review
Mycosis fungoides (MF) is a rare disease and is the most common form of cutaneous T cell lymphoma. Topical chlormethine (CL) gel is the first cytotoxic chemotherapy gel that was specifically developed for treatment of MF. In this review, we provide an overview of all available data on the use of CL gel for treatment of patients with MF. On the basis of the current data collected, CL gel is highly effective, with good response rates observed both in clinical trial and real-world settings. While the gel is approved for monotherapy, it is also used in combination with concomitant skin-directed or systemic therapies in clinical practice. Responses to CL gel treatment can be rapid, but they also frequently occur with a delayed onset of up to 6 months. This indicates that continued treatment with CL gel is important. CL gel has a manageable safety profile, with most adverse events being mild and skin related. Contact dermatitis is one of the more common skin-related adverse events to occur with CL gel treatment that can potentially lead to treatment discontinuation. The data from the literature indicate that patients being treated with CL gel should be monitored carefully, and that dermatitis must be managed effectively to allow patients to continue treatment and achieve the best possible response to treatment.
Topics: Clinical Trials as Topic; Gels; Humans; Lymphoma, T-Cell, Cutaneous; Mechlorethamine; Mycosis Fungoides; Skin Neoplasms
PubMed: 35852707
DOI: 10.1007/s12325-022-02219-w -
Chemical Research in Toxicology Apr 2022Cytotoxic blistering agents such as sulfur mustard and nitrogen mustard (HN2) were synthesized for chemical warfare. Toxicity is due to reactive chloroethyl side chains...
Cytotoxic blistering agents such as sulfur mustard and nitrogen mustard (HN2) were synthesized for chemical warfare. Toxicity is due to reactive chloroethyl side chains that modify and damage cellular macromolecules including DNA and proteins. In response to DNA damage, cells initiate a DNA damage response directed at the recruitment and activation of repair-related proteins. A central mediator of the DNA damage response is p53, a protein that plays a critical role in regulating DNA repair. We found that HN2 causes cytosolic and nuclear accumulation of p53 in HaCaT keratinocytes; HN2 also induced post-translational modifications on p53 including S15 phosphorylation and K382 acetylation, which enhance p53 stability, promote DNA repair, and mediate cellular metabolic responses to stress. HN2 also cross-linked p53, forming dimers and high-molecular-weight protein complexes in the cells. Cross-linked multimers were also modified by K48-linked ubiquitination indicating that they are targets for proteasome degradation. HN2-induced modifications transiently suppressed the transcriptional activity of p53. Using recombinant human p53, HN2 alkylation was found to be concentration- and redox status-dependent. Dithiothreitol-reduced protein was more efficiently cross-linked indicating that p53 cysteine residues play a key role in protein modification. LC-MS/MS analysis revealed that HN2 directly alkylated p53 at C124, C135, C141, C176, C182, C275, C277, H115, H178, K132, and K139, forming both monoadducts and cross-links. The formation of intermolecular complexes was a consequence of HN2 cross-linked cysteine residues between two molecules of p53. Together, these data demonstrate that p53 is a molecular target for mustard vesicants. Modification of p53 likely mediates cellular responses to HN2 including DNA repair and cell survival contributing to vesicant-induced cytotoxicity.
Topics: Chromatography, Liquid; Cysteine; Humans; Keratinocytes; Mechlorethamine; Tandem Mass Spectrometry; Tumor Suppressor Protein p53
PubMed: 35312310
DOI: 10.1021/acs.chemrestox.1c00420 -
Cancer Dec 1977The feasibility of employing adjuvant topical mechlorethamine after electron beam therapy in the treatment of patients with mycosis fungoides is demonstrated. Patients... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The feasibility of employing adjuvant topical mechlorethamine after electron beam therapy in the treatment of patients with mycosis fungoides is demonstrated. Patients treated with a planned adjuvant topical mechlorethamine schedule had a median disease-free interval of 25 months compared to 17 months for the group treated with electron beam therapy alone. Projected relapse-free survivals are slightly better in the adjuvant group--37% versus 29%. Patients receiving adjuvant topical mechlorethamine after the electron beam were observed to have a low incidence of contact allergy to the medication. The topical medication can be continued if a contact allergy develops by using a planned desensitization program. We currently treat all mycosis fungoides patients with electron beam therapy, randomizing half to receive adjuvant topical mechlorethamine.
Topics: Administration, Topical; Dermatitis, Contact; Female; Humans; Male; Mechlorethamine; Middle Aged; Mycosis Fungoides; Radiotherapy, High-Energy; Remission, Spontaneous; Skin Neoplasms; Time Factors
PubMed: 412580
DOI: 10.1002/1097-0142(197712)40:6<2851::aid-cncr2820400615>3.0.co;2-x