Nitrosourea represents one of the most active classes of chemotherapeutic alkylating agents for metastatic melanoma. Treatment with nitrosoureas caused severe systemic side effects which hamper its clinical use. Here, we provide pharmacological evidence that reactive oxygen species (ROS) induction and IKKβ inhibition cooperatively enhance nitrosourea-induced cytotoxicity in melanoma cells. We identified SC-514 as a ROS-inducing IKKβ inhibitor which enhanced the function of nitrosoureas. Elevated ROS level results in increased DNA crosslink efficiency triggered by nitrosoureas and IKKβ inhibition enhances DNA damage signals and sensitizes nitrosourea-induced cell death. Using xenograft mouse model, we confirm that ROS-inducing IKKβ inhibitor cooperates with nitrosourea to reduce tumor size and malignancy in vivo. Taken together, our results illustrate a new direction in nitrosourea treatment, and reveal that the combination of ROS-inducing IKKβ inhibitors with nitrosoureas can be potentially ...
Title:A Short Review on the Synthetic Strategies of Duocarmycin Analogs that are Powerful DNA Alkylating Agents. VOLUME: 15 ISSUE: 5. Author(s):Pravin C. Patil, Vijay Satam and Moses Lee. Affiliation:Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.. Keywords:Antitumor-antibiotics, apoptosis, centanamycin, duocarmycins, tafuramycin A.. Abstract:The duocarmycins and CC-1065 are members of a class of DNA minor groove, AT-sequence selective, and adenine-N3 alkylating agents, isolated from Streptomyces sp. that exhibit extremely potent cytotoxicity against the growth of cancer cells grown in culture. Initial synthesis and structural modification of the cyclopropa[c] pyrrolo[3,2-e]indole (CPI) DNA-alkylating motif as well as the indole non-covalent binding region in the 1980s have led to several compounds that entered clinical trials as potential anticancer drugs. However, due to significant systemic toxicity none of the analogs have passed clinical evaluation. As a result, ...
Alkylating Antineoplastic Agents: A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)
Melflufen is designed for targeted delivery of alkylating moieties to tumor cells. In contrast to other alkylating agents that are hydrophilic, the lipophilicity of melflufen leads to rapid and extensive distribution into tissues and cells. Inside cells, melflufen may directly bind DNA or is readily metabolized by intracellular peptidases into the well-known antitumor compound melphalan, or by esterases into des-ethylmelflufen, which also has alkylating properties. Due to the high activity of peptidases and esterases in human tumor cells, the formation of melflufens metabolites is rapid in these cells with subsequent inflow of more melflufen. Since des-ethylmelflufen and melphalan are relatively hydrophilic, there is a possibility for intracellular trapping of these alkylators ...
The major alkylating agents are the nitrogen mustards and the nitrosoureas. These drugs covalently alkylate various cellular constituents. Most importantly for
... definition, any of various potentially cytotoxic, carcinogenic, and mutagenic substances: used therapeutically to destroy cells, especially proliferating cancer cells. See more.
Read "The effect of the Primary Structure of DNA on Induction of Mutations by Alkylating Agents, Russian Journal of Genetics" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Learn about the veterinary topic of Alkylating Agents. Find specific details on this topic and related topics from the Merck Vet Manual.
Leukemia is not an important factor in the natural history of breast cancer, though its association with breast cancer therapy has frequently been reported. There are reports of therapy related hematological malignancies in breast cancer dated as early as 1980s describing the incidence as 1.68 ± .33% at 10 years with chemotherapy vis a vis 0.06% to 0.27% with surgery alone [1]. In 1992, a large case-control study of 82,700 women with breast cancer demonstrated a relative risk of developing AML as 2.4 for radiotherapy, 10 for therapy with alkylating agents and 17.4 when the two were used in combination [2] The chemotherapy regimens employed during these studies used mainly melphalan as alkylating agent and that for long durations (12 to 24 months) [1, 2]. Though over the last decade anthracyclines along with safer alkylating agents have formed the main core of the breast cancer therapy; the modern chemotherapy is not entirely safe. The more recent reports in the background of anthracycline and ...
Cisplatin is similar to the bifunctional alkylating agents. It covalently binds to DNA and disrupts DNA function. After cisplatin enters the cells, the chloride ligands are replaced by water molecules. This reaction results in the formation of positively charged platinum complexes that react with the nucleophilic sites on (...). ...
Melphalan is a DNA alkylating agent; induces cytotoxicity through the formation of stable interstrand and intrastrand crosslinks within DNA which inhibits growth of PC-3 cells (IC50 values are 0.074 and 0.77 μM for sequential dosing and single dosing respectively). Learn More ...
Reporting biases in published trials were first identified in 1986.1 Published randomized studies of combination chemotherapy compared with treatment with an alkylating agent as first line treatment for ovarian cancer showed a significant survival advantage for combination chemotherapy. Unpublished cancer trial registry data from the same studies, however, showed no such advantage.2 Similarly, in the treatment of multiple myeloma, registry data suggested a smaller survival advantage for combination chemotherapy (over prednisone and an alkylating agent) than the results of published studies. The author who reported the discrepancy concluded that his findings "demonstrate the value and importance of an international registry of all clinical trials."1Subsequent evidence for biased and selective reporting included prompt or delayed publication depending on whether trial results were positive or negative3 and more favorable results and conclusions in published studies funded by industry than in those ...
Reporting biases in published trials were first identified in 1986.1 Published randomized studies of combination chemotherapy compared with treatment with an alkylating agent as first line treatment for ovarian cancer showed a significant survival advantage for combination chemotherapy. Unpublished cancer trial registry data from the same studies, however, showed no such advantage.2 Similarly, in the treatment of multiple myeloma, registry data suggested a smaller survival advantage for combination chemotherapy (over prednisone and an alkylating agent) than the results of published studies. The author who reported the discrepancy concluded that his findings "demonstrate the value and importance of an international registry of all clinical trials."1Subsequent evidence for biased and selective reporting included prompt or delayed publication depending on whether trial results were positive or negative3 and more favorable results and conclusions in published studies funded by industry than in those ...
S. B. J. Kan, H. Maruyama, M. Akakura, T. Kano, K. Maruoka, Angew. Chem. Int. Ed., 56, 9487-9491 (2017). (Highlighted in SYNFACTS, 2017, 985). Alkylsilyl Peroxides as Alkylating Agents in the Copper-Catalyzed Selective Mono-N-Alkylation of Primary Amides and Arylamines ...
O6-methylguanine-DNA methyltransferase plays vital roles in preventing induction of mutations and cancer as well as cell death related to alkylating agents. Mice defective in the Mgmt gene, encoding the methyltransferase, were used to evaluate cell death-inducing and tumorigenic activities of therapeutic agents which have alkylation potential. Mgmt-/- mice were considerably more sensitive to dacarbazine, a monofunctional triazene, than were wild-type mice, in terms of survival. When dacarbazine was administered i.p. to 6-week-old mice and survival at 30 days was enumerated, LD50 values of Mgmt-/- and Mgmt+/+ mice were 20 and 450 mg/kg body wt, respectively. Increased sensitivity of Mgmt-/- mice to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), a bifunctional nitrosourea, was also noted. On the other hand, there was no difference in survival of Mgmt+/+ and Mgmt-/- mice exposed to cyclophosphamide, a bifunctional nitrogen mustard. It appears that dacarbazine and ...
Many chemotherapeutic agents have been associated with pulmonary toxicities. Busulfan was the first chemotherapeutic drug with evidence of drug-induced lung disease 6. Other alkylating agents, such as cyclophophamide and chlorambucil have been clearly associated with pulmonary toxicity as well 7. Dacarbazine, which is closely related to temozolomide has been associated with pulmonary adverse effects only when used in combination with fotemustine, a nitrosourea agent 8.. Temozolomide is an imidazotetrazine compound and a derivative of the alkylating agent dacarbazine (second-generation oral alkylating agent). Temozolomide has proven activity against recurrent glioma 9. In a recent randomised trial, concomitant and adjuvant temozolomide chemotherapy with radiation significantly improved progression free survival and overall survival in glioblastoma multiforme patients 2.. Various adverse reactions have been reported, but they are usually mild to moderate and in the majority of cases do not require ...
Bendamustine has demonstrated clinical efficacy in the treatment of haematological malignancies and distinguish itself from other alkylating agents. The mechanistic and clinical differences associated with Bendamustine may be related to its structural features including a benzimidazole ring, although the mechanism of action is poorly understood. Understanding the molecular mechanism of Bendamustine could explain the therapeutic efficacy and identify potential biomarkers for response. The Bendamustine-DNA interaction in naked DNA, cytotoxicity, and ICL formation and repair (unhooking) in naked DNA or in cell lines and patient multiple myeloma cells by the single cell gel electrophoresis (comet) assay, were analyzed. DNA damage response (DDR) and potential mechanisms of acquired resistance to Bendamustine were also evaluated. Bendamustine alkylated DNA at guanine-N7 positions, produced ICLs in naked DNA and in cells, and demonstrated a cytotoxic effect comparable to conventional ICL drugs ...
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene (or their equivalents).[1] An alkyl group is a piece of a molecule with the general formula CnH2n+1, where n is the integer depicting the number of carbons linked together. For example, a methyl group (n = 1, CH3) is a fragment of a methane molecule (CH4). Alkylating agents use selective alkylation by adding the desired aliphatic carbon chain to the previously chosen starting molecule. This is one of many known chemical syntheses. Alkyl groups can also be removed in a process known as dealkylation. Alkylating agents are often classified according to their nucleophilic or electrophilic character. In oil refining contexts, alkylation refers to a particular alkylation of isobutane with olefins. For upgrading of petroleum, alkylation produces a premium blending stock for gasoline.[2]. In medicine, alkylation of DNA is used in ...
DNA damaging alkylating agents are present abundantly in the environment and also produced endogenously.The majority of the DNA adducts caused by such alkylating agents would be in double-stranded DNA. However, single-strand- specific lesions canarise when DNA double helix is temporarily unwound during replication or recombination. The N1 position of purines and the N3 of pyrimidines, which are normally protected from alkylation by base pairing in duplex DNA, can be alkylated in single-stranded DNA. The Escherichia coliAlkB protein is an oxidative demethylase that repairs such alkylatedbases present in single stranded DNA. Although AlkB function was known in great detail, its regulation was poorly characterized. I hypothesized that some proteins might directly interact with AlkB to regulate its function.. ...
This trial is investigating the tolerability of irinotecan, temozolomide and bevacizumab in combination with existing high dose alkylator based chemotherapy for
The great diversity in sarcoma phenotypes and genotypes make this disease family exceptionally challenging. Phenotypically diverse human adult and pediatric sarcoma lines were screened with a defined set of drugs and compounds (22). Sarcoma genomics have been explored using cell lines and clinical specimens (12, 23). This study presents gene-expression data derived from exon array data as well as microRNA data, which are available in GEO.. One study goal was to identify small-molecule drugs for further examination in sarcoma. The constellation relational map provides visualization of the sarcoma screen for compounds with a dynamic range of at least one log in IC50 across the panel (Fig. 1). The clusters are compounds with similar patterns of response. Aurora kinase inhibitors form a distinct cluster adjacent to bifunctional alkylating agents, topoisomerase I and II inhibitors. Taxanes and microtubule fragmenters form a cluster adjacent to topoisomerase I and II inhibitors. The results are ...
Consistent results from three case-control studies and a pooled analysis, totaling 555 head and neck cancer cases and 792 controls, suggest that genetic variations in MGMT84, MGMT143, and XRCC1399 influence susceptibility to head and neck cancer. Moreover, the MGMT143 variant may modify alcohol-related risk.. MGMT encodes O6-alkylguanine DNA alkyltransferase, which preferentially removes O6-guanine alkyl adducts caused by carcinogens, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone found in tobacco smoke (40), and the Val143 allele has previously been related to increased lung cancer risk in two small studies (each with ∼130 cases; refs. 28, 41). In our study, Val143 was associated with reduced head and neck cancer risk, particularly among heavy drinkers. In vivo and in vitro experiments show that MGMT-mediated repair of alkylated DNA is reduced by treatment with ethanol or its primary metabolite, acetaldehyde (42, 43), possibly due to MGMT inhibition (44). Although the functional ...
Anesthetic agent-induced liver damage information including symptoms, diagnosis, misdiagnosis, treatment, causes, patient stories, videos, forums, prevention, and prognosis.
Failure to Diagnose Antituberculous agent-induced liver damage including overlooked symptoms and complications for under-diagnosed medical conditions.
Principal Investigator:SUGIYAMA Hiroshi, Project Period (FY):1997 - 1998, Research Category:Grant-in-Aid for Scientific Research (B), Section:展開研究, Research Field:Synthetic chemistry
At left, photoreceptor cells of the retina have undergone severe damage after treatment with an alkylating agent. This damage is exacerbated by the DNA repair
Generic name Melphalan hydrochloride Pronunciation MEL-fa-lan HIGH-droe-KLOR-ide Brand name(s), other common name(s) EvomelaTM Drug type Alkylating agent How the drug is given
Alkeran tablets and injection contain the active ingredient melphalan, which is a type of chemotherapy medicine to treat cancer called an alkylating agent.
In this article you will know all of the Main drugs used in cancer treatment. Know about Mitotic Inhibitors, Antibiotics, Antimetabolites and Alkylating
Diazomethane is toxic by inhalation or by contact with the skin or eyes (TLV 0.2ppm). Symptoms include chest discomfort, headache, weakness and, in severe cases, collapse.[14] Symptoms may be delayed. Deaths from diazomethane poisoning have been reported. In one instance a laboratory worker consumed a hamburger near a fumehood where he was generating a large quantity of diazomethane, and died four days later from fulminating pneumonia.[15] Like any other alkylating agent it is expected to be carcinogenic, but such concerns are overshadowed by its serious acute toxicity. CH2N2 may explode in contact with sharp edges, such as ground-glass joints, even scratches in glassware.[16] Glassware should be inspected before use and preparation should take place behind a blast shield. Specialized kits to prepare diazomethane with flame-polished joints are commercially available. The compound explodes when heated beyond 100 °C, exposed to intense light, alkali metals, or calcium sulfate. Use of a blast ...
Lomustine (INN), abbreviated as CCNU (original brand name (formerly available) is CeeNU, now marketed as Gleostine), is an alkylating nitrosourea compound used in chemotherapy. It is closely related to semustine and is in the same family as streptozotocin. It is a highly lipid-soluble drug,[2] thus it crosses the blood-brain barrier. This property makes it ideal for treating brain tumors, which is its primary use, although it is also used to treat Hodgkin lymphoma as a second-line option.[3] Lomustine has a long time to nadir (the time when white blood cells reach their lowest number). Unlike carmustine, lomustine is administered orally. It is a monofunctional alkylating agent, alkylates both DNA and RNA, has the ability to cross-link DNA.[4] As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.[5] Lomustine is cell-cycle nonspecific. It has also been used in veterinary practice as a treatment for mast cell tumors in ...
TY - JOUR. T1 - Unraveling innate immunity using large scale N-ethyl-N-nitrosourea mutagenesis. AU - Hoebe, Kasper. AU - Beutler, B.. PY - 2005/5. Y1 - 2005/5. N2 - With the mouse genome almost entirely sequenced and readily accessible to all who wish to examine it, the challenge across most biological disciplines now lies in the decipherment of gene and protein function rather than in the realm of gene identification per se. In the field of innate immunity, forward genetic methods have repeatedly been applied to identify key sensors, adapters, and effector molecules. However, most spontaneous mutations that affect innate immune function have been mapped and cloned, and the need for new monogenic phenotypes has been felt evermore keenly. N-Ethyl-N-nitrosourea (ENU) mutagenesis is an efficient tool for the creation of aberrant monogenic innate immune response phenotypes. In this review, we will discuss the potential of the forward genetic approach and ENU mutagenesis to identify new genes and new ...
Introduction. High dose melphalan 200mg/m2 (MEL200) followed by autologous stem cell transplantation (ASCT) is the standard of care for fit patients with Multiple Myeloma (MM). Bendamustine has been shown to induce responses in MM resistant to other alkylating agents. Our prior Phase I trial, adding bendamustine to MEL200, demonstrated no additional toxicity above that expected with MEL200 alone (Mark et. al. BBMT 2013). A phase 2 trial of bendamustine/MEL200 conditioning was conducted to evaluate treatment efficacy. Objective and Methods. This single arm, open-label, phase II study was designed to establish the efficacy of Bendamustine (225 mg/m2) in combination with MEL200 in patients undergoing first ASCT for MM. Patients 18 to 75 years with confirmed MM, prior induction therapy, adequate mobilization (at least 2x106 of CD34+ hematopoietic stem cells), Karnofsky performance status ,70% and life expectancy ,12 weeks were eligible for screening. Major exclusion criteria included ...
After relapse or after early progression on first-line treatment, the prognosis of multiple myeloma (MM) patients is unfavourable, and the search for new treatment regimens, including drugs with novel mechanisms of action is essential.. Bendamustine and bortezomib have shown high activity boch in first-line regimens and pre-treated patients. The novel mechanism of action of the proteasome inhibitor and the non-cross resistance of bendamustine to other alkylating agents established in the first-line treatment of multiple myeloma seem to recommend a combination of the two drugs for salvage therapy (second-line regimen). Finally, the promising response data in a series of relapsing MM patients treated with bendamustine, bortezomib and prednisone support this assumption, as well as the feasibility and tolerability of the combination.. In summary, there is some evidence for a favorable risk/benefit ratio for the combination of bendamustine, bortezomib and a corticoid drug, warranting the exploration ...
TY - JOUR. T1 - Prevention of N-methyl-N-nitrosourea-induced breast cancer by α-fetoprotein (AFP)-derived peptide, a peptide derived from the active site of AFP. AU - Parikh, Rahul R.. AU - Gildener-Leapman, Neil. AU - Narendran, Amithi. AU - Lin, Hung Yun. AU - Lemanski, Nicole. AU - Bennett, James A.. AU - Jacobson, Herbert I.. AU - Andersen, Thomas T.. PY - 2005/12/1. Y1 - 2005/12/1. N2 - Purpose: α-Fetoprotein (AFP) is a protein of pregnancy associated with a decrease in lifetime risk of breast cancer in parous women. A synthetic, cyclic nonapeptide has been developed that mimics the antioncogenic active site of AFP. To test the hypothesis that the AFP-derived peptide (AFPep) can prevent breast cancer, the N-methyl-N-nitrosourea-induced breast cancer model was used in rats. Experimental Design: AFPep was given daily by injection beginning 10 days after N-methyl-N-nitrosourea treatment and continued for 23 days (a time designed to mimic pregnancy) or for other times to assess efficacy as a ...
Treg-cell function is compromised in rheumatoid arthritis (RA). As the master regulator of Treg cells, FOXP3 controls development and suppressive function. Stable Treg-cell FOXP3 expression is epigenetically regulated; constitutive expression requires a demethylated Treg-specific demethylated region. Here, we hypothesised that methylation of the FOXP3 locus is altered in Treg cells of established RA patients. Methylation analysis of key regulatory regions in the FOXP3 locus was performed on Treg cells from RA patients and healthy controls. The FOXP3 Treg-specific demethylated region and proximal promoter displayed comparable methylation profiles in RA and healthy-donor Treg cells. We identified a novel differentially methylated region (DMR) upstream of the FOXP3 promoter, with enhancer activity sensitive to methylation-induced silencing. In RA Treg cells we observed significantly reduced DMR methylation and lower DNA methyltransferase (DNMT1/3A) expression compared with healthy Treg cells. Furthermore,
A vesicant and necrotizing irritant destructive to mucous membranes, mechlorethamine is an alkylating drug. It was formerly used as a war gas. The hydrochloride is used as an antineoplastic in Hodgkins disease and lymphomas. It causes severe gastrointestinal and bone marrow damage. [PubChem] The FDA granted marketing approval for the orphan drug Valchlor (mechlorethamine) gel on August 23, 2013 for the topical treatment of stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma (CTCL) in patients who have received prior skin-directed therapy. Each tube of Valchlor contains 0.016% of mechlorethamine which is equivalent to 0.02% mechlorethamine HCL.
Mechanism: Valchlor is a gel formulation of mechlorethamine, an alkylating agent which inhibits rapidly proliferating cells. Valchlor is specifically indicated for the topical treatment of Stage IA and IB mycosisfungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. Valchlor is supplied as a gel for topical administration. The recommendation is to apply a thin film of Valchlor gel once daily to affected areas of the skin. Upon improvement, treatment with Valchlor can be restarted at a reduced frequency of once every 3 days. If reintroduction of treatment is tolerated for at least one week, the frequency of application can be increased to every other day for at least one week and then to once daily application if tolerated. Valchlor is a gel formulation of mechlorethamine, also known as nitrogen mustard, an alkylating agent which inhibits rapidly proliferating cells. ...
Epichlorohydrin (ECH) is a DNA bifunctional alkylating agent that has been shown to form DNA inter-strand cross-links in vitro at the N7 position of guanines at the 5-GNC and 5-GC consensus sequences. We used the quantitative polymerase chain reaction (QPCR) to monitor the formation of in vivo ECH lesions in 6C2 chicken erythroid progerutor cells. Three distinct loci were investigated in order to determine the effect of ECH reactivity in different levels of chromatin condensation. The sites consisted of an open locus of the nuclear genome, a closed locus of the nuclear genome, and a naked locus of the mitochondrial genome. We found that ECH alkylation was preferentially targeted towards the nuclear sites and that chromatin structure had no effect upon ECH reactivity. Repair assays of the three sites revealed that there appears to be no repair of ECH lesions in the nuclear genome.
The drug shows high potency and activity in various experimental models including P-gp- and MRP1-expressing multidrug resistant tumors as well as tumors resistant to platinum derivatives, alkylating agents and topoisomerase I and II inhibitors. Nemorubicin has a peculiar mechanism of action requiring NER activity for its full cytotoxicity. Cell lines defective in NER, which show an increased sensitivity to classical alkylating agents, display a three-four fold resistance to nemorubicin. Interestingly, L1210 murine leukemia cells selected for resistance to nemorubicin (L1210/MMDX) show a collateral sensitivity to both platinum derivatives and alkylating agents and are more sensitive (about 4-5 times) to UV light. In addition, these cells are not able to repair UV-induced damage on transfected DNA (host -cell reactivation assay), suggesting that the NER system might be involved in mediating the cytotoxic activity of nemorubicin. The aim of the present study was to evaluate the possible presence of ...
Consistent results from three case-control studies and a pooled analysis, totaling 555 head and neck cancer cases and 792 controls, suggest that genetic variations in MGMT84, MGMT143, and XRCC1399 influence susceptibility to head and neck cancer. Moreover, the MGMT143 variant may modify alcohol-related risk.. MGMT encodes O6-alkylguanine DNA alkyltransferase, which preferentially removes O6-guanine alkyl adducts caused by carcinogens, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone found in tobacco smoke (40), and the Val143 allele has previously been related to increased lung cancer risk in two small studies (each with ∼130 cases; refs. 28, 41). In our study, Val143 was associated with reduced head and neck cancer risk, particularly among heavy drinkers. In vivo and in vitro experiments show that MGMT-mediated repair of alkylated DNA is reduced by treatment with ethanol or its primary metabolite, acetaldehyde (42, 43), possibly due to MGMT inhibition (44). Although the functional ...
... is used to treat the symptoms of several types of cancer. Mechlorethamine treats only the symptoms of cancer but does not treat the cancer itself. Mechlorethamine is also sometimes injected into body spaces around the heart, lungs, or stomach to treat fluid retention in these areas caused by cancer...
4.1 Polymorphisms and mutations are both variations in DNA sequence and can arise through the same mechanisms. We use the term polymorphism to refer to DNA variants that are relatively common in populations. Mutations affect the phenotype.. 4.2 Misreading of bases during replication can lead to substitution and can be caused by things like tautomerism, DNA alkylating agents, and irradiation.. 4.3 Looping out of DNA on the template strand during replication; strand breakage, due to radiation and other mutagens; and (discussed in earlier chapters) chromosomal aberrations such as deletions and translocations.. 4.4 Looping out of DNA on the growing strand during replication; transposition; and (discussed in earlier chapters) chromosomal aberrations such as duplications, insertions, and translocation.. 4.5 Benzopyrene is one of many hazardous compounds present in smoke. Benzopyrene is an intercalating agent, which slides between the bases of the DNA molecule, distorting the shape of the double helix, ...
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In a phase II study reported in the Journal of Clinical Oncology, Chawla et al found that the combination of a hypoxia-activated alkylating prodrug (TH-302) and doxorubicin was active in first-line treatment of advanced soft-tissue sarcoma. TH-302 is a prodrug of the cytotoxic alkylating agent.... ...
Function: Corrects defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents ...
A catalyst composition that is the combination of or the reaction product of ingredients comprising (a) a nickel-containing compound, (b) an alkylating agent, (c) a fluorine-containing compound, and (d) a chlorine-containing compound.
Were found to alkylate all oxygens and nitrogens in nucleic acids , whereas a host of more moderately reactive electrophilic agents typically target nitrogens
AA-CW236 is a novel non-pseudosubstrate inhibitor of human O(6)-alkylguanine DNA methyltransferase (MGMT) by targeting MGMT active site Cys145 for covalent modification.
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In response to replication stress, a phospho-signaling cascade is activated and required for coordination of DNA repair and replication of damaged templates (intra-S phase checkpoint). How phospho-signaling coordinates the DNA replication stress response is largely unknown. We employed state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS/MS) approaches to generate high-coverage and quantitative proteomic and phospho-proteomic profiles during replication stress in yeast, induced by continuous exposure to the DNA alkylating agent methyl methanesulfonate (MMS). We identified 32,057 unique peptides representing the products of 4,296 genes, and 22,061 unique phosphopeptides representing the products of 3,183 genes. 542 phosphopeptides (mapping to 339 genes) demonstrated an abundance change of ≥ 2-fold in response to MMS. The screen enabled detection of nearly all of the proteins known to be involved in the DNA damage response, as well as many novel MMS-induced phosphorylations. We ...
The alkylating agents are a group of strong disinfecting chemicals that act by replacing a hydrogen atom within a molecule with an alkyl group (CnH2n+1), thereby inactivating enzymes and nucleic acids ([link]). The alkylating agent formaldehyde (CH2OH) is commonly used in solution at a concentration of 37% (known as formalin) or as a gaseous disinfectant and biocide. It is a strong, broad-spectrum disinfectant and biocide that has the ability to kill bacteria, viruses, fungi, and endospores, leading to sterilization at low temperatures, which is sometimes a convenient alternative to the more labor-intensive heat sterilization methods. It also cross-links proteins and has been widely used as a chemical fixative. Because of this, it is used for the storage of tissue specimens and as an embalming fluid. It also has been used to inactivate infectious agents in vaccine preparation. Formaldehyde is very irritating to living tissues and is also carcinogenic; therefore, it is not used as an ...
Here, we demonstrate that OTUD4 may serve as a master regulator of alkylation damage resistance through stabilization of the human AlkB homologues. A number of distinct lines of evidence support this role for OTUD4. First, OTUD4 interacts specifically with ALKBH2 and ALKBH3 and encodes a K48‐specific DUB (Fig 1). Consistently, ALKBH3 is subjected to K48‐linked ubiquitination and proteasomal degradation (Fig 2A-D). OTUD4 antagonizes ALKBH3 ubiquitination and stabilizes both ALKBH2 and ALKBH3 in vivo (Fig 2E-H). ALKBH3 protein levels do not correlate well with ALKBH3 mRNA levels in various tumor cell lines but do correlate with OTUD4 levels (Supplementary Fig S2). Finally, overexpression of ALKBH3 in PC‐3 cells, which depend primarily on ALKBH3 instead of ALKBH2 for alkylation damage resistance, is sufficient to rescue alkylation damage sensitivity upon loss of OTUD4 (Fig 7G).. What is most striking is that we find OTUD4 catalytic activity to be apparently dispensable for its stabilization ...
Looking for online definition of alkylate in the Medical Dictionary? alkylate explanation free. What is alkylate? Meaning of alkylate medical term. What does alkylate mean?
Solid neoplasms may contain deficient or poorly functional vascular beds, a property that leads to the formation of hypoxic tumor cells, which form a therapeutically resistant cell population within the tumor that is difficult to eradicate by ionizing irradiation and most existing chemotherapeutic agents. As an approach to the therapeutic attack of hypoxic cells, we have measured the cytotoxicity and DNA lesions produced by the bioreductive alkylating agents mitomycin C and porfiromycin, two structurally similar antibiotics, in oxygen-deficient and aerobic cells. Mitomycin C and porfiromycin were preferentially cytotoxic to hypoxic EMT6 cells in culture, with porfiromycin producing a greater differential kill of hypoxic EMT6 cells relative to their oxygenated counterparts than did mitomycin C. Chinese hamster ovary cells were more resistant to these quinone antibiotics; although in this cell line, porfiromycin was significantly more cytotoxic to hypoxic cells than to aerobic cells, and the ...
Home » Busulfan. Busulfan (Science: chemical) An alkylating agent having a selective immunosuppressive effect on bone marrow. It has been used in the palliative treatment of chronic myeloid leukaemia, but although symptomatic relief is provided, no permanent remission is brought about. According to the fourth annual report on carcinogens (ntp 85-002, 1985), busulfan is listed as a known carcinogen. Pharmacological action: alkylating agents, antineoplastic agent, alkylating, carcinogens, immunosuppressive agents. chemical name: 1,4-Butanediol, dimethanesulfonate ...
Mechlorethamine - Get up-to-date information on Mechlorethamine side effects, uses, dosage, overdose, pregnancy, alcohol and more. Learn more about Mechlorethamine
Therapeutic radiation increases AML risk, particularly if given concomitantly with alkylating agents. Two categories of therapy-related AML have been described. Patients exposed to alkylating agents (eg, cyclophosphamide, melphalan, nitrogen mustard) can develop AML after a latency period of 4 to 8 years, which is often associated with abnormalities of chromosomes 5 and/or 7. Exposure to agents that inhibit the DNA repair enzyme topoisomerase II (eg, etoposide) is also associated with secondary AML with a shorter latency period, usually 1 to 3 years (4). Benzene, smoking, dyes, herbicides, and pesticides have been implicated as potential risk factors for development of AML (5). ...
The 7-bromoacetyl-7-desacetyl (BrAcFsk) and 7-chloroacetyl-7-desacetyl (CIAcFsk) analogs of forskolin were synthesized as alkylating agents to study the high affinity binding sites for forskolin. BrAcFsk and CIAcFsk activated adenylate cyclase in human platelet membranes with EC50 values of about 20 and 12 microM, respectively. Both analogs increased cyclic AMP in human platelets; however, they were less potent that forskolin. Forskolin inhibited [3H]forskolin binding to human platelet membranes with an IC50 of 20 nM, whereas BrAcFsk and CIAcFsk inhibited [3H] forskolin binding with IC50 values of 0.1 microM. Pretreatment of intact platelets with 10 microM BrAcFsk caused a 90% irreversible loss in [3H]forskolin binding sites, whereas pretreatment with 10 microM CIAcFsk led to a loss of 55% of the binding sites. The loss of binding sites occurred within 5 min for BrAcFsk and within 30 min for CIAcFsk. The time required for the loss of binding sites produced by either alkylating agent was ...
The appearance of electrophoretically separable isozyme patterns is specific both to type of tissue and to its stage of development (Markert & Møller, 1959). In abnormally developing embryonic systems there are alterations in the time of initial appearance and the persistence of isozymes from a variety of metabolic areas (Johnson & Spinuzzi, 1966, 1968). In malformed embryos from folic-aciddeficient rats the altered zymogram patterns of esterases from abnormal limbs were different from those of abnormal kidneys, yet differentiation of zymograms from the normal hearts of these embryos was unaltered. This implies a correlation between altered tissue-specific zymogram patterns and abnormally developing systems, though no causal relationship has as yet been shown (Johnson, 1968). Moreover, when tibial hemimelia in the rat was elicited by two different teratogens-a folic acid antagonist, 9-methylpteryol-glutamic acid (PGA), and the alkylating agent N-nitroso-N-methylurea (NNMU)-there were similar ...
Alkylation reactions represent an important organic transformation to form C-C bonds. In addition to conventional approaches with alkyl halides or sulfonates as alkylating agents, the use of unactivated olefins for alkylations has become attractive from both cost and sustainability viewpoints. This Review summarizes transition-metal-catalyzed alkylations of various
Introduction: After lymphoma the risk of secondary cancer namely lung cancer increases. Treatment (alkylating agents, radiotherapy) and smoking are known risk factors. Aims: To report on patients with lung cancer (LC) after lymphoma (LY), focusing on disease characteristics, detection methods and clinical outcomes. Methods: Retrospective study of patients diagnosed in a single institution with LC and previous LY from 1992 to 2012. Data regarding LY characteristics and treatment, smoking history and LC stage, histology and survival were obtained from medical records. Results: Of the 44 patients 43% had Hodgkin and 57% non Hodgkin lymphoma. All had known risk factors: 13 (30%) thoracic radiotherapy, 21 (48%) alkylating chemotherapy, 34 (75%) smoking habits. Median time between diagnoses was 9,5 years (±9.3).Thirteen were female (30%). Median age at LC diagnosis was 60 years (±13). Stage distribution was: 21(48%) IV, 10(23%) III; 13(30%) I/II. PS was 0/1 in 36(81%) patients. Diagnosis was ...
The nitrosoureas are alkylating agents that are highly lipid soluble and share similar pharmacological and clinical properties. Carmustine (BCNU), lomustine
165 medications are known to interact with mechlorethamine. Includes Adriamycin (doxorubicin), Adrucil (fluorouracil), Ascriptin Enteric (aspirin).
During the annual meeting, new preclinical data on ImmunoGens novel ADCs, IMGN632 and IMGN779 will be presented. IMGN632, is a CD123-targeting ADC while IMGN779, targets CD33. Both investigational agents use ImmunoGens new family of indolino-benzodiazepine cancer-killing agents called IGNs. Scientists at ImmunoGen designed IGN payloads to alkylate DNA without crosslinking it. The data being presented in both oral as well as poster presentations demonstrates that DNA-alkylating IGNs are ultra-potent, yet provide increased tolerability compared with DNA crosslinking versions.. "Accelerating our earlier-stage portfolio with an emphasis on our IGN ADCs is one of [our] strategic priorities, and we believe the IMGN632 and IMGN779 preclinical … further demonstrates why we are excited about the potential of these programs," explained Richard Gregory, Ph.D., executive vice president and chief scientific officer of ImmunoGen.. The preclinical data to be presented shows activity of IMGN632 in multiple ...
Hydrogen, Lead, Ability, Alkaline Comet Assay, Alkylation, Alkylators, Blood, Cancer, Cell, Cells, Chromatography, Comet Assay, Concentration, Concentrations, DNA, DNA Damage, Epithelial Cells, Ethylene Oxide, Gas Chromatography, Human
Mechanism of Action Prodrug; pharmacologically active free thiol metabolite can reduce the toxic effects of cisplatin (is available to bind to , and detoxify, reactive metabolites of cisplatin). It can also act as a scavenger of free radicals that may be generated in tissues exposed to cisplatin. It also protects against cell damage from radiation and other alkylators. Other mechanisms may be responsible for protection against paclitaxel toxicity and for therapeutic effect in MDS.. ...
Health Canada has approved a new treatment option for relapsed patients with chronic lymphocytic leukemia (CLL) and for follicular lymphoma (FL). Gilead Sciences Canadas ZYDELIG™ (idelalisib) tablets, received a Notice of Compliance in combination with rituximab for the treatment of patients with relapsed CLL. ZYDELIG also received a Notice of Compliance with Conditions as a stand-alone treatment for patients with FL who have undergone at least two prior systemic regimens and are resistant to both rituximab and an alkylating agent.. CLL and FL are slow-growing incurable blood cancers, most common in adults 50 years of age and older, that can lead to life-threatening complications such as anemia, serious infection and bone marrow failure requiring treatment. As conventional chemotherapy is not curative for CLL or FL, nearly all patients will eventually relapse after their initial treatment. At relapse, patients often face fewer treatment options because they may be unable to tolerate ...
Alkylating Agents, Breast, Cancers, Cholesterol, Drugs, Epoxide Hydrolase, Epoxides, Metabolism, Report, Styrene, Tamoxifen, Treatment
Find quality suppliers and manufacturers of 61380-07-2(2-Thiopheneethanol,2-methanesulfonate) for price inquiry. where to buy 61380-07-2(2-Thiopheneethanol,2-methanesulfonate).Also offer free database of 61380-07-2(2-Thiopheneethanol,2-methanesulfonate) including MSDS sheet(poisoning, toxicity, hazards and safety),chemical properties,Formula, density and structure, solution etc.
The O(6)-alkylguanine-DNA alkyltransferase inactivator O(6)-benzylguanine was administered to BALB/c mice either alone or before exposure to 1,3-bis(2-chloroethyl)-1-nitrosourea to study the role of the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase in the protection of the testis against anti-cancer O(6)-alkylating agents. Exposure of the mice to 1, 3-bis(2-chloroethyl)-1-nitrosourea or O(6)-benzylguanine alone did not produce any marked testicular toxicity at the times studied. Testicular O(6)-alkylguanine-DNA alkyltransferase concentrations were assayed between 0 and 240 min after O(6)-benzylguanine treatment and were shown to be , 95% depleted 15 min after treatment with O(6)-benzylguanine and remained at , 95% at all the times assayed. Histological examination, the reduction in testicular mass and the induction of spermatogenic cell apoptosis showed that this depletion significantly potentiated 1, 3-bis(2-chloroethyl)-1-nitrosourea-induced testicular damage after treatment. Major ...
We investigated sequence-specific DNA alkylation using conjugates between the N-methylpyrrole (Py)-N-methylimidazole (Im) polyamide and the DNA alkylating agent, chlorambucil, or 1-(chloromethyl)-5-hydroxy-1, 2-dihydro-3H-benz[e]indole (seco-CBI). Polyamide-chlorambucil conjugates 1-4 differed in the position at which the DNA alkylating chlorambucil moiety was bound to the Py-Im polyamide. High-resolution denaturing polyacrylamide gel electrophoresis (PAGE) revealed that chlorambucil conjugates 1-4 alkylated DNA at the sequences recognized by the Py-Im polyamide core moiety. Reactivity and sequence specificity were greatly affected by the conjugation position, which reflects the geometry of the alkylating agent in the DNA minor groove. Polyamide-seco-CBI conjugate 5 was synthesized to compare the efficacy of chlorambucil with that of seco-CBI as an alkylating moiety for Py-Im polyamides. Denaturing PAGE analysis revealed that DNA alkylation activity of polyamide-seco-CBI conjugate 5 was similar ...
Another amino acid-like drug is the antineoplastic agent melphalan. Tumor cells spend less time in resting phases than normal cells so at any given time, they are more likely to be metabolically active than most normal host cells. The rationale behind incorporating an alkylating function in a molecule resembling a primary cellular metabolite was to get a greater safety margin by fooling tumor cells into taking up the toxin preferentially. ...
Accepted name: DNA-3-methyladenine glycosylase II. Reaction: Hydrolysis of alkylated DNA, releasing 3-methyladenine, 3-methylguanine, 7-methylguanine and 7-methyladenine. Other name(s): deoxyribonucleate 3-methyladenine glycosidase II; 3-methyladenine DNA glycosylase II; DNA-3-methyladenine glycosidase II; AlkA. Systematic name: alkylated-DNA glycohydrolase (releasing methyladenine and methylguanine). Comments: Involved in the removal of alkylated bases from DNA in Escherichia coli (cf. EC 2.1.1.63 methylated-DNA [protein]-cysteine S-methyltransferase).. Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 89287-38-7. References:. 1. Evensen, G. and Seeberg, E. Adaptation to alkylation resistance involves the induction of a DNA glycosylase. Nature 296 (1982) 773-775. [PMID: 7040984]. 2. Karran, P., Hjelmgren, T. and Lindahl, T. Induction of a DNA glycosylase for N-methylated purines is part of the adaptive response to alkylating agents. Nature 296 (1982) 770-773. ...
The nitrosourea drugs, a class of DNA alkylating agents related to nitrogen mustards, include(BCNU),(CCNU), semustine (methyl CCNU), and chloroethylnitrosourea (Sar-CNU). Nitrosourea drugs are used to treat lymphoma, brain tumors, melanoma, and other
Several lines of evidence point to the existence of endogenous cellular compounds that can alkylate DNA and cause spontaneous, alkylation-induced mutation. First, the alkyl lesionsO 6MeG and 7MeG have been detected in DNA from humans, mice, and rats that were not patently exposed to alkylating agents (16, 24, 33, 44). The 3MeA free base can also be found in human urine, and some of this 3MeA burden is believed to result from release of endogenously alkylated DNA bases (24,34). Second, bacteria and yeast that are deficient in the DNA methyltransferases that repair mutagenic O 6MeG lesions display elevated spontaneous mutation rates (20, 36, 45,47, 51-53). In E. coli, the majority of the ada ogt-dependent spontaneous mutations have been shown to be G:C-to-A:T transitions (20, 47), consistent with their arising from replication past endogenous O 6MeG residues (20).. In 1996, Taverna and Sedgwick (45) reported that ada ogt E. coli defective in the moa gene, which encodes a cofactor involved in ...
EMEA (Europe, Middle East and Africa) Mitomycin C Market 2017 Forecast to 2022. This report studies the Mitomycin C market, Mitomycin C is an antibiotic which acts as a double-stranded DNA alkylating agent. It covalently crosslinks DNA, inhibiting DNA synthesis and cell proliferation It acts by way of reductive activation either through low pH or NAD(P)H:quinone oxidoreductase (DT-diaphorase) or NADH cytochrome c reductase .... January 2018 , $4480 ,View Details>> ...
EMEA (Europe, Middle East and Africa) Mitomycin C Market 2017 Forecast to 2022. This report studies the Mitomycin C market, Mitomycin C is an antibiotic which acts as a double-stranded DNA alkylating agent. It covalently crosslinks DNA, inhibiting DNA synthesis and cell proliferation It acts by way of reductive activation either through low pH or NAD(P)H:quinone oxidoreductase (DT-diaphorase) or NADH cytochrome c reductase .... January 2018 , $4480 ,View Details>> ...
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults, and is universally fatal. The DNA alkylating agent temzolomide (TMZ) is part of the standard-of-care for GBM. However, these tumors eventually develop therapy-driven resistance and inevitably recur. While loss of mismatch repair (MMR) and re-expression of MGMT have been shown to underlie chemoresistance in a fraction of GBMs, resistance mechanisms operating in the remaining GBMs are not well understood. In order to better understand the molecular basis for therapy-driven TMZ resistance, mice bearing orthotopic GBM xenografts were subjected to protracted TMZ treatment, and cell lines were generated from the primary (untreated) and recurrent (TMZ-treated) tumors. As expected, the cells derived from primary tumors were sensitive to TMZ while the cells from the recurrent tumors were significantly resistant to the drug. Importantly, the acquired resistance to TMZ in the recurrent lines was not driven by ...
TY - JOUR. T1 - A genome-wide miRNA screen revealed miR-603 as a MGMT-regulating miRNA in glioblastomas. AU - Kushwaha, Deepa. AU - Ramakrishnan, Valya. AU - Ng, Kimberly. AU - Steed, Tyler. AU - Nguyen, Thien. AU - Futalan, Diahnn. AU - Akers, Johnny C.. AU - Sarkaria, Jann. AU - Jiang, Tao. AU - Chowdhury, Dipanjan. AU - Carter, Bob S.. AU - Chen, Clark C.. PY - 2014. Y1 - 2014. N2 - MGMT expression is a critical determinant for therapeutic resistance to DNA alkylating agents. We previously demonstrated that MGMT expression is posttranscriptionally regulated by miR-181d and other miRNAs. Here, we performed a genome-wide screen to identify MGMT regulating miRNAs. Candidate miRNAs were further tested for inverse correlation with MGMT expression in clinical specimens. We identified 15 candidate miRNAs and characterized the top candidate, miR-603. Transfection of miR-603 suppressed MGMT mRNA/protein expression in vitro and in vivo; this effect was reversed by transfection with antimiR-603. miR-603 ...
Alkylating agents constitute a large class of DNA‐damaging agents that generate both mutagenic and cytotoxic DNA lesions. Much of our understanding of alkylation damage repair is from studies on Escherichia coli, in particular on the adaptive (Ada) response, which involves the upregulation of four genes: ada, aidB, alkA and alkB (Sedgwick et al, 2007). The Ada protein is a multifunctional DNA methyltransferase that also acts as a transcriptional activator of the response. The exact function of AidB, a flavin‐binding protein, remains to be explained and AlkA is a DNA glycosylase with a broad specificity. AlkB catalyses the demethylation of 1‐methyladenine and 3‐methylcytosine in DNA and RNA, coupled to the decarboxylation of 2‐oxoglutarate (2OG) to succinate and CO2 (Falnes et al, 2002; Trewick et al, 2002). Homologues of AlkB have been identified in species ranging from bacteria to humans; eight human homologues (ABH) have been described, but only two, ABH2 and ABH3, are known to ...
Oral alkylating drugs, alone and in combination therapy with steroids, have been extensively evaluated in the upfront treatment of WM. The greatest experience with oral alkylator therapy has been with chlorambucil, which has been administered on both a continuous (i.e. daily dose schedule) as well as an intermittent schedule. Patients receiving chlorambucil on a continuous schedule typically receive 0.1 mg/kg per day, whilst on the intermittent schedule patients will typically receive 0.3 mg/kg for 7 days, every 6 weeks. In a prospective randomized study, Kyle et al.109 reported no significant difference in the overall response rate between these schedules, although interestingly the median response duration was greater for patients receiving intermittent versus continuously dosed chlorambucil (46 vs. 26 months). Despite the favorable median response duration in this study for use of the intermittent schedule, no difference in the median overall survival was observed. Moreover, an increased ...
The tissue and cellular distribution of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase) is an important question in relation to the response of tumour and normal tissues to chemotherapeutic regimes employing alkylating agents such as methyltriazenes and nitrosoureas. In order to examine this issue by immunostaining, we have raised a rabbit antiserum to apparently pure recombinant human enzyme. The antiserum is highly specific and sensitive, detecting a band at 24 kDa on western blots of crude extracts of ATase-expressing human lymphoblastoid cells, liver and melanoma. Adjacent sections of acetone or formalin fixed normal human liver and subcutaneous malignant melanoma were reacted with preimmune serum or antiserum and an immunoperoxidase detection system with silver enhancement was used to locate binding of the primary antibody to the antigen. In sections reacted with preimmune serum or with antigen-preadsorbed antiserum, only faint cytoplasmic and little or no nuclear ...
Alkylating agents exert a wide range of biological effects in both pro- and eukaryotes and there is ever increasing evidence that these effects are mediated via alkylation at the O6position of...
D4337 - 89(2017) Standard Test Methods for Analysis of Linear Detergent Alkylates , linear alkylbenzenes, linear detergent alkylates ,,
Despite advances in surgery and intensive investigation into novel therapies, the overall 2-year survival rate for malignant gliomas (i.e., grades III and IV) remains ,20% (1 , 14) . For the most common diagnostic types, adjuvant therapy with radiation and alkylating agent-based chemotherapy modestly increases response rates and survival times (5 , 11) . However, adjuvant therapy provides no benefit to a sizeable fraction of patients and seldom produces long term remission. In addition, the modest benefit conferred depends greatly on patient and clinical variables, including age, neurological status, and histology (1 , 2 , 34) . Intrinsic and acquired resistance to alkylators and radiation are major factors affecting outcome. Hence, characterization of mechanisms underlying resistance is essential to identify potential targets for antiresistance therapies and to develop potential prognostic markers to guide adjuvant therapies. Our results suggest that Ap endo activity promotes resistance to ...
Non-toxic DAlCs, especially lighter dimethyl- and diethyl-carbonate, are regarded as very green alkylating reagents, particularly when coupled with metal-exchanged Y- and X-faujasites as catalysts. These reactions are selective, free from wastes or byproducts, and often require no additional solvent other th
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Definition of busulfan - A drug which is an alkylating agent with a destructive effect on bone marrow, used especially in the treatment of chronic myeloid
3804 Introduction: Inadequate tumor vascularization and/or anti-vascular effects of cancer chemotherapy contribute to anticancer drugs failure. We pursued physiological drug resistance of cancer chemotherapy in mouse breast cancer models using magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI). Methods: All animal experiments were conducted according to the institutional guidelines. Anesthetized SCID mice with orthotopic MCF-7 breast cancer were immobilized in the probe and maintained under gas anesthesia (Isoflurane 0.5%, 1 l/min). 13C-Labeled-temozolomide ([13C]TMZ) or temozolomide (TMZ: Temodar® capsule), alkylating agent, was used as a model drug. Two hundred microliter of [13C]TMZ (50 mM)/dimethyl-β-cyclodextrin (100 mM) inclusion complex was infused into the mouse via an i.p. catheter. Three-dimensional indirect 1H/13C MRSI was performed with an 8x8x8 matrix for a 16 mm isotropic field of view. During 3D map acquisition, a total of 400 μl of inclusion complex was ...
Cancer drugs can be divided into two general classes: CELL CYCLE SPECIFIC DRUGS (CCS; esp. plant alkaloids and antimetabolites), and CELL CYCLE NON-SPECIFIC DRUGS (CCNS; esp. alkylating agents and some natural products). Antineoplastic agents can also be organized according to their chemical class, mechanism of action, therapeutic use or their toxicities ...
1P7M: Solution structure and base perturbation studies reveal a novel mode of alkylated base recognition by 3-methyladenine DNA glycosylase I
BACKGROUND: Many studies aimed at retargeting adenovirus (Ad) rationally focus on genetic modification of fiber, which is the primary receptor-binding protein of Ad. Retargeted fibers ultimately require functional validation in the viral context. METHODS: Lentiviral vectors (LV) were used to express fiber variants in cells. Infections with a fiber gene-deleted Ad vector yielded fiber-pseudotyped viruses. An enzyme-linked immunosorbent assay and slot blot-based assays probed target binding-ability of retargeted fibers. Differential treatments with an alkylating agent prior to western blot analysis allowed for examination of intra- and extracellular redox states of fibers. RESULTS: In the present study, LV-based fiber-pseudotyping of Ad is presented as an accelerated means to test new fibers. LV-mediated gene transfer yielded stable and uniform populations of fiber variant-expressing cells. These populations were found to effectively support fiber-pseudotyping of Ad. As a secondary objective of ...
Submission of the final clinical study report for study 101-09, A Phase 2 Study to Assess the Efficacy and Safety of Idelalisib in Subjects with Indolent B-Cell Non-Hodgkin Lymphomas Refractory to Rituximab and Alkylating Agents. This submission was an Annex II post-authorisation measure (ANX 002) and a category I commitment in the Zydelig Risk Management Plan (RMP).. The SmPC was updated to include the safety and efficacy data from Study 101-09 and the SmPC and PIL were updated to remove the inverted black triangle and requirement for additional monitoring as this submission fulfilled the last outstanding commitment in the Product Information Annex II.. We also took the opportunity to remove ofatumumab from the SmPC and PIL indication statement following the withdrawal of the Arzerra (ofatutumumab) licence in the EU. ...
The present invention pertains to a method for manufacturing alkylate oil using a composite ionic liquid as catalyst. A mixture of isobutane and C4 olefins is used as the raw material, and a composite
Two Chinese hamster ovary (CHO) cell variants differ substantially in their sensitivity to N-methyl-N -nitro-N-nitrosoguanidine (MNNG). The resistant clone (Cl 3) was isolated from the sensitive...
Glycosphingolipids (GSLs) are ubiquitous components of plasma membrane in all mammalian cells, and they are concentrated in specialized microdomains for cell s...
In a screen for organogenesis defects in N-ethyl-N-nitrosourea (ENU)-induced mutant mice, we discovered a line carrying a mutation in Colgaft1 [collagen beta(1-O)galactosyltransferase type 1], which is required for proper ...
In a screen for organogenesis defects in N-ethyl-N-nitrosourea (ENU)-induced mutant mice, we discovered a line carrying a mutation in Colgaft1 [collagen beta(1-O)galactosyltransferase type 1], which is required for proper ...
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