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Proceedings of the Royal Society of... Aug 1963
Topics: Multiple Myeloma; Neoplasms; Neoplasms, Plasma Cell; Nitrogen Mustard Compounds; Plasmacytoma; Urethane
PubMed: 14052447
DOI: No ID Found -
Proceedings of the Royal Society of... Aug 1963
Topics: Chlorambucil; Cyclophosphamide; Genetic Diseases, X-Linked; Hodgkin Disease; Humans; Leukemia, Hairy Cell; Lymphatic Diseases; Melphalan; Nitrogen Mustard Compounds; Peptide Nucleic Acids; Prednisolone; Prednisone; Severe Combined Immunodeficiency; Thiotepa
PubMed: 14052445
DOI: No ID Found -
Journal of Hematology & Oncology May 2013Chronic lymphocytic leukemia (CLL) is a heterogeneous group of B-cell neoplasm. CLL is typically sensitive to a variety of cytotoxic agents, but relapse frequently... (Review)
Review
Chronic lymphocytic leukemia (CLL) is a heterogeneous group of B-cell neoplasm. CLL is typically sensitive to a variety of cytotoxic agents, but relapse frequently occurs with conventional approaches. The treatment of CLL is evolving rapidly with the introduction of novel drugs, such as bendamustine, ofatumumab, lenalidomide, ibrutinib, idelalisib, veltuzumab, XmAb5574, navitoclax, dasatinib, alvespimycin, and TRU-016. This review summarizes the most current clinical experiences with these agents in the treatment of CLL.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Humans; Lenalidomide; Leukemia, Lymphocytic, Chronic, B-Cell; Nitrogen Mustard Compounds; Thalidomide
PubMed: 23680477
DOI: 10.1186/1756-8722-6-36 -
Analytical Chemistry Mar 2021Route determination of sulfur mustard was accomplished through comprehensive nontargeted screening of chemical attribution signatures. Sulfur mustard samples prepared...
Route determination of sulfur mustard was accomplished through comprehensive nontargeted screening of chemical attribution signatures. Sulfur mustard samples prepared via 11 different synthetic routes were analyzed using gas chromatography/high-resolution mass spectrometry. A large number of compounds were detected, and multivariate data analysis of the mass spectrometric results enabled the discovery of route-specific signature profiles. The performance of two supervised machine learning algorithms for retrospective synthetic route attribution, orthogonal partial least squares discriminant analysis (OPLS-DA) and random forest (RF), were compared using external test sets. Complete classification accuracy was achieved for test set samples (2/2 and 9/9) by using classification models to resolve the one-step routes starting from ethylene and the thiodiglycol chlorination methods used in the two-step routes. Retrospective determination of initial thiodiglycol synthesis methods in sulfur mustard samples, following chlorination, was more difficult. Nevertheless, the large number of markers detected using the nontargeted methodology enabled correct assignment of 5/9 test set samples using OPLS-DA and 8/9 using RF. RF was also used to construct an 11-class model with a total classification accuracy of 10/11. The developed methods were further evaluated by classifying sulfur mustard spiked into soil and textile matrix samples. Due to matrix effects and the low spiking level (0.05% w/w), route determination was more challenging in these cases. Nevertheless, acceptable classification performance was achieved during external test set validation: chlorination methods were correctly classified for 12/18 and 11/15 in spiked soil and textile samples, respectively.
Topics: Gas Chromatography-Mass Spectrometry; Mass Spectrometry; Mustard Gas; Retrospective Studies; Soil
PubMed: 33709707
DOI: 10.1021/acs.analchem.0c04555 -
Environmental Health Perspectives Nov 1992The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and... (Review)
Review
The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and small quantities of the organic arsenical Lewisite [dichloro(2-chlorovinyl) arsine; agent L]. These agents can be dispersed in liquid, aerosol, or vapor form and are capable of producing severe chemical burns upon direct contact with tissue. Moist tissues such as the eyes, respiratory tract, and axillary areas are particularly affected. Available data summarizing acute dose response in humans and laboratory animals are summarized. Vesicant agents are also capable of generating delayed effects such as chronic bronchitis, carcinogenesis, or keratitis/keratopathy of the eye under appropriate conditions of exposure and dose. These effects may not become manifest until years following exposure. Risk analysis derived from carcinogenesis data indicates that sulfur mustard possesses a carcinogenic potency similar to that of benzo[a]pyrene. Because mustard agents are alkylating compounds, they destroy individual cells by reaction with cellular proteins, enzymes, RNA, and DNA. Once begun, tissue reaction is irreversible. Mustard agents are mutagenic; data for cellular and laboratory animal assays are presented. Reproductive effects have not been demonstrated in the offspring of laboratory rats. Acute Lewisite exposure has been implicated in cases of Bowen's disease, an intraepidermal squamous cell carcinoma. Lewisite is not known to generate reproductive or teratogenic effects.
Topics: Animals; Arsenic Poisoning; Arsenicals; Cell Membrane Permeability; Chemical Warfare; DNA Damage; Dermatitis, Irritant; Female; Humans; Irritants; Keratitis; Lethal Dose 50; Lung Neoplasms; Male; Mustard Gas; Mutation; Pregnancy; Reproduction; Respiratory Tract Diseases
PubMed: 1486858
DOI: 10.1289/ehp.9298259 -
Chemical Research in Toxicology Feb 2016N,N-Bis-(2-chloroethyl)-phosphorodiamidic acid (phosphoramide mustard, PM) and N,N-bis-(2-chloroethyl)-amine (nornitrogen mustard, NOR) are the two biologically active...
N,N-Bis-(2-chloroethyl)-phosphorodiamidic acid (phosphoramide mustard, PM) and N,N-bis-(2-chloroethyl)-amine (nornitrogen mustard, NOR) are the two biologically active metabolites of cyclophosphamide, a DNA alkylating drug commonly used to treat lymphomas, breast cancer, certain brain cancers, and autoimmune diseases. PM and NOR are reactive bis-electrophiles capable of cross-linking cellular biomolecules to form covalent DNA-DNA and DNA-protein cross-links (DPCs). In the present work, a mass spectrometry-based proteomics approach was employed to characterize PM- and NOR-mediated DNA-protein cross-linking in human cells. Following treatment of human fibrosarcoma cells (HT1080) with cytotoxic concentrations of PM, over 130 proteins were found to be covalently trapped to DNA, including those involved in transcriptional regulation, RNA splicing/processing, chromatin organization, and protein transport. HPLC-ESI(+)-MS/MS analysis of proteolytic digests of DPC-containing DNA from NOR-treated cells revealed a concentration-dependent formation of N-[2-[cysteinyl]ethyl]-N-[2-(guan-7-yl)ethyl]amine (Cys-NOR-N7G) conjugates, confirming that it cross-links cysteine thiols of proteins to the N7 position of guanines in DNA. Cys-NOR-N7G adduct numbers were higher in NER-deficient xeroderma pigmentosum cells (XPA) as compared with repair proficient cells. Furthermore, both XPA and FANCD2 deficient cells were sensitized to PM treatment as compared to that of wild type cells, suggesting that Fanconi anemia and nucleotide excision repair pathways are involved in the removal of cyclophosphamide-induced DNA damage.
Topics: Alkylating Agents; Cell Line, Tumor; Chromatography, High Pressure Liquid; DNA; DNA Adducts; Humans; Nitrogen Mustard Compounds; Peptides; Phosphoramide Mustards; Proteins; Proteomics; Spectrometry, Mass, Electrospray Ionization
PubMed: 26692166
DOI: 10.1021/acs.chemrestox.5b00430 -
British Medical Journal Sep 1979
Topics: Adolescent; Adult; History, 20th Century; Hodgkin Disease; Humans; Lymphography; Nitrogen Mustard Compounds; Palliative Care; United Kingdom
PubMed: 91404
DOI: 10.1136/bmj.2.6190.587 -
Annals of Surgery Aug 1953
Topics: Aneurysm; Humans; Mechlorethamine; Nitrogen Mustard Compounds
PubMed: 13066011
DOI: 10.1097/00000658-195308000-00007 -
Proceedings of the Royal Society of... Dec 1973
Review
Topics: Carmustine; Chlorambucil; Colonic Neoplasms; Cyclophosphamide; Drug Therapy, Combination; Fluorouracil; Humans; Methotrexate; Nitrogen Mustard Compounds; Rectal Neoplasms; Vincristine
PubMed: 4591085
DOI: No ID Found -
Blood Aug 2014Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and... (Review)
Review
Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and treatment strategy have been proposed as part of the consensus panels of International Workshops on WM (IWWM). As part of the IWWM-7 and based on recently published and ongoing clinical trials, the panels updated treatment recommendations. Therapeutic strategy in WM should be based on individual patient and disease characteristics (age, comorbidities, need for rapid disease control, candidacy for autologous transplantation, cytopenias, IgM-related complications, hyperviscosity, and neuropathy). Mature data show that rituximab combinations with cyclophosphamide/dexamethasone, bendamustine, or bortezomib/dexamethasone provided durable responses and are indicated for most patients. New monoclonal antibodies (ofatumumab), second-generation proteasome inhibitors (carfilzomib), mammalian target of rapamycin inhibitors, and Bruton's tyrosine kinase inhibitors are promising and may expand future treatment options. A different regimen is typically recommended for relapsed or refractory disease. In selected patients with relapsed disease after long-lasting remission, reuse of a prior effective regimen may be appropriate. Autologous stem cell transplantation may be considered in young patients with chemosensitive disease and in newly diagnosed patients with very-high-risk features. Active enrollment of patients with WM in clinical trials is encouraged.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Bendamustine Hydrochloride; Boronic Acids; Bortezomib; Clinical Trials as Topic; Consensus Development Conferences as Topic; Disease Progression; Everolimus; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors; Nitrogen Mustard Compounds; Pyrazines; Rituximab; Salvage Therapy; Sirolimus; Treatment Outcome; Vidarabine; Waldenstrom Macroglobulinemia
PubMed: 25027391
DOI: 10.1182/blood-2014-03-565135