A folic acid derivative used as a rodenticide that has been shown to be teratogenic.
Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)
An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.
A peptide that is a homopolymer of glutamic acid.
An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 1.5.1.3.
An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.
A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.
An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or 6-mercaptopurine to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8.

Phase I study of escalating doses of edatrexate in combination with paclitaxel in patients with metastatic breast cancer. (1/155)

Motivated by the observation of preclinical synergy, a Phase I dose escalation study of edatrexate in combination with a 3-h paclitaxel infusion was performed in patients with advanced breast cancer to determine the maximum tolerated dose (MTD) of edatrexate and the toxicities associated with this combination and to report preliminary observations of efficacy with this novel combination. Thirty-six patients were enrolled in this Phase I trial. Thirty-five eligible patients were treated every 21 days in cohorts of at least three patients and were assessable for toxicity. One patient was ineligible due to hyperbilirubinemia. Stepwise dose escalations of edatrexate were administered until grade >3 nonhematological dose-limiting toxicities were reported. The initial dose level of edatrexate was 180 mg/m2; subsequent cohorts were treated with escalating doses of edatrexate (210, 240, 270, 300, 350, and 400 mg/m2). Edatrexate was administered by i.v. infusion over 1 h. Paclitaxel was administered 24 h later at a fixed dose of 175 mg/m2 as a 3-h infusion with standard dexamethasone, diphenhydramine, and cimetidine premedication. The MTD of edatrexate was reached at the 350 mg/m2 level in this study. Grade 3 diarrhea was seen in one patient at the 300 and 400 mg/m2 dose levels, requiring dose reductions. Two patients experienced grade 4 stomatitis at the 400 mg/m2 dose level and also required dose reduction, establishing the MTD as 350 mg/m2. Grade 3 nausea and vomiting were noted in two of three patients at the highest dose level. Of 35 patients, 4 patients reported grade 3 myalgias and 1 patient reported grade 3 neurosensory complaints, which were seen mostly at the 350 and 400 mg/m2 dose levels; however, 1 patient reported grade 3 myalgias at 180 mg/m2. No cumulative neurotoxicity was observed, and no patient experienced an allergic reaction to paclitaxel. In 23 patients with bidimensionally measurable disease, there were four complete (17%) and seven partial responses, with an overall response rate of 48% (95% confidence interval, 27-69%). All of the responses were seen in patients who had not received prior chemotherapy for stage IV disease. The median duration of response was not assessable because many responding patients went on to receive high-dose chemotherapy treatment with stem cell support. The combination of edatrexate and paclitaxel for treatment of metastatic breast cancer is a feasible and safe regimen. The MTD of edatrexate was 350 mg/m2 when combined with a 3-h infusion of paclitaxel (175 mg/m2) given 24 h later. Activity was noted even among patients who had relapsed shortly after receiving methotrexate- and/or doxorubicin-containing adjuvant regimens. Additional studies evaluating the sequences and dosing schema for this combination are warranted to improve the response proportion and define the duration of the response.  (+info)

Folylpolyglutamyl synthetase gene transfer and glioma antifolate sensitivity in culture and in vivo. (2/155)

BACKGROUND: Although antifolates are popular agents for use in chemotherapy, they display minimal toxicity against slow-growing tumors and are toxic to actively replicating cells in normal tissues. These drugs are converted intracellularly into polyglutamate derivatives by the enzyme folylpolyglutamyl synthetase (FPGS). Because tumors with high expression of FPGS often respond to nontoxic antifolate doses, we investigated whether augmenting tumoral FPGS activity by gene delivery would enhance tumoral antifolate sensitivity. METHODS: 9L rat gliosarcoma cells were stably transfected with a human FPGS complementary DNA (cDNA), producing 9L/FPGS cells. The sensitivity of these cells to the antifolates methotrexate and edatrexate was measured in culture and in subcutaneous tumors, as was their ability to increase the chemosensitivity of nearby nontransfected cells, i.e., a bystander effect. The antifolate sensitivity of nonselected cells transduced with a hybrid amplicon vector that expressed FPGS was also ascertained. RESULTS: In comparison with 9L cells, 9L/FPGS cells displayed enhanced sensitivity to 4-hour pulses of antifolate. Subcutaneous 9L/FPGS tumors responded as well to methotrexate given every third day as 9L tumors did to daily treatment. A modest bystander effect was observed with edatrexate treatment in culture and in vivo. The observed bystander effect appeared to result from the release of antifolates by transfected cells after the removal of extracellular drug. In culture, enhanced antifolate sensitivity was also seen in other stably transfected rodent and human glioma cell lines, including one with high pre-existing FPGS activity, and in canine and human glioblastoma cell lines transduced with a vector bearing FPGS cDNA. CONCLUSIONS: FPGS gene delivery enhances the antifolate sensitivity of several glioma cell lines and merits further evaluation as a therapeutic strategy.  (+info)

Phase I study of the sequential administration of edatrexate and paclitaxel in patients with advanced solid tumors. (3/155)

BACKGROUND: The antifolate edatrexate and the microtubule-stabilizing agent paclitaxel have both demonstrated single-agent activity in lung and breast cancer. In vitro, the sequential combination of edatrexate followed by paclitaxel produced synergistic antitumor effects. This trial was designed to find the maximum tolerated doses of edatrexate and paclitaxel when given every two weeks utilizing this sequential schedule. PATIENTS AND METHODS: Thirty-four patients with solid tumors received edatrexate intravenously on days 1 and 15 and paclitaxel intravenously as a three-hour infusion on days 2 and 16 of each 28-day cycle. Edatrexate was escalated from 40 to 120 mg/m2 and the paclitaxel dose fixed at 135 mg/m2. When the maximum-tolerated dose was not reached, edatrexate was fixed at 120 mg/m2 and paclitaxel escalated to 175 and 210 mg/m2. RESULTS: All 34 patients were assessable. The maximum tolerated doses were 120 mg/m2 of edatrexate and 210 mg/m2 of paclitaxel. Grade 3 myalgia, peripheral neuropathy, leukopenia, and an infusion-related reaction occurred. Eight patients with non-small-cell lung cancer and one with bladder cancer achieved major objective responses. CONCLUSIONS: The recommended phase II doses are 120 mg/m2 of edatrexate days 1 and 15 and 175 mg/m2 of paclitaxel as a three-hour infusion days 2 and 16 of a 28 day cycle. These results warrant phase II trials of the combination leading to phase III studies comparing the two drugs to a single agent to confirm the preclinical evidence of synergy.  (+info)

Dihydrofolate reductase from Kaposi's sarcoma-associated herpesvirus. (4/155)

Kaposi's sarcoma-associated herpesvirus (KSHV) is the first human virus known to encode dihydrofolate reductase (DHFR), an enzyme required for nucleotide and methionine biosynthesis. We have studied the purified KSHV-DHFR enzyme in vitro and analyzed its expression in cultured B-cell lines derived from primary effusion lymphoma (PEL), an AIDS-associated malignancy. The amino acid sequence of KSHV-DHFR is most similar to human DHFR (hDHFR), but the viral enzyme contains an additional 23 amino acids at the carboxyl-terminus. The viral DHFR, overexpressed and purified from E. coli, was catalytically active in vitro. The K(m) of KSHV-DHFR for dihydrofolate (FH(2)) was 2.4 microM, which is significantly higher than the K(m) of recombinant hDHFR (rhDHFR) for FH(2) (390 nM). K(m) values for NADPH were similar for the two enzymes, about 1 microM. KSHV-DHFR was inhibited by folate antagonists such as methotrexate (K(i): 200 pM), aminopterin (K(i): 610 pM), pyrimethamine (K(i): 29 nM), trimethoprim (K(i): 2.3 microM), and piritrexim (K(i): 3.9 nM). In all cases, K(i) values for these folate antagonists were higher for KSHV-DHFR than for rhDHFR. The viral enzyme was expressed at levels two- to tenfold higher than hDHFR in PEL cell lines as an early lytic cycle gene. KSHV-DHFR mRNA and protein appeared from 6 to 24 h after chemical induction of the KSHV lytic cycle. Epitope-tagged KSHV-DHFR and rhDHFR both localized to the nucleus of transfected cells, while other KSHV nucleotide metabolism genes localized to the cytoplasm. DHFR activity was not essential for viral replication in cultured PEL cells. Since hDHFR was not detectable in peripheral blood mononuclear cells (PBMCs), KSHV-DHFR may function to provide increased DHFR activity in vivo in infected cells that have little or none of their own enzyme.  (+info)

A spontaneous murine melanoma lung metastasis comprised of host x tumor hybrids. (5/155)

Cells from a lung metastasis, arising from Cloudman S91 melanoma cells implanted s.c. in the tail of a BALB/c nu/nu mouse, were comprised chiefly of host x tumor hybrids. These lung metastasis cells showed: (a) 30-40% increased DNA content; (b) resistance to 10(-4) M hypoxanthine, 4 x 10(-7) M aminopterin, and 1.6 x 10(-5) M thymidine (HAT) + G418; and (c) the presence in genomic DNA of genes for both wt and albino tyrosinase, reflecting the DBA/2J (Cloudman S91) and BALB/c mouse genotypes, respectively. Individual clones of lung metastasis cells expressed enhanced pigmentation, motility, and responsiveness to MSH/IBMX, a behavior similar to that recently reported for artificially generated melanoma x macrophage fusion hybrids. These similarities suggested that the host fusion partner generating the lung metastasis hybrids might have been a macrophage, although formal proof for this was not possible. The results provide the first direct evidence that host x tumor hybridization could serve as an initiating mechanism for melanoma metastasis.  (+info)

Trans-stimulation effects of folic acid derivatives on methotrexate transport by rat renal organic anion transporter, OAT-K1. (6/155)

We examined the pharmacological role of the renal organic anion transporter OAT-K1, which localizes predominantly in the brush-border membranes of proximal straight tubules, in the urinary excretion of methotrexate and the possibility of its contribution to "folinic acid rescue." With Madin-Darby canine kidney (MDCK) cells stably transfected with OAT-K1 cDNA, OAT-K1-mediated methotrexate accumulation was inhibited in the presence of various folic acid derivatives. These derivatives included aminopterin, 5-methyltetrahydrofolic acid, unlabeled methotrexate, folinic acid (citrovorum factor, leucovorin), and folic acid with apparent inhibition constant values of 0.5, 1.2, 1.8, 8.2, and 14.1 microM, respectively. In contrast, 10 microM taurocholic acid and sulfobromophthalein did not inhibit OAT-K1-mediated methotrexate accumulation. In addition, methotrexate efflux was stimulated in the presence of inwardly directed gradients of aminopterin, 5-methyltetrahydrofolic acid, unlabeled methotrexate, folinic acid, and folic acid, but not of uric acid, taurocholic acid, and glutathione, indicating that OAT-K1-mediated methotrexate efflux is stimulated by a folic acid derivatives exchange. In conclusion, OAT-K1 was suggested to enhance the apical efflux of highly accumulated methotrexate in tubular epithelial cells and contribute at least in part to folinic acid rescue by exchanging intracellular methotrexate for extracellular folinic acid.  (+info)

Phase I and pharmacokinetic study of 10-propargyl-10-deazaaminopterin, a new antifolate. (7/155)

The 10-deazaaminopterins are a new class of rationally designed antifolates demonstrating greater antitumor effects than methotrexate in murine tumor models and human tumor xenografts. Their design was aimed at improving membrane transport and polyglutamylation in tumor cells, resulting in increased intracellular accumulation and enhanced cytotoxicity. Compared with other 4-aminofolate analogues, 10-propargyl-10-deazaaminopterin (PDX) is the most efficient permeant for the RFC-1-mediated internalization and substrate for folylpolyglutamate synthetase. PDX demonstrates greater in vitro and in vivo antitumor efficacy than methotrexate or edatrexate. We undertook a Phase I study with PDX to identify the potential toxicities and define an optimal dose and schedule. Thirty-three patients were enrolled, all of whom had non-small cell lung cancer (NSCLC) and were treated previously with a median of two prior chemotherapy regimens. Initially, PDX was administered weekly for 3 weeks in a 4-week cycle. Mucositis requiring dose reduction and/or delay in the first cycle occurred in four of six patients treated at the initial dose level (30 mg/m2), making this the maximal tolerated dose for PDX given on this schedule. The treatment schedule was then modified to every 2 weeks. Twenty-seven patients were treated twice weekly with a total of 102 four-week cycles (median, 2 cycles/patient). Mucositis was the dose-limiting toxicity, with grade 3 and 4 mucositis occurring in the first two patients treated at the 170 mg/m2 dose level. Other toxicities were mild and reversible. No neutropenia was observed. The recommended Phase II dose is 150 mg/m2 biweekly. At that dose level, the mean area under the curve was 20.6 micromol x h, and the mean terminal half-life was 8 h. Two patients with stage IV NSCLC had major objective responses, and five patients had stable disease for 7 (two patients), 9 (one patient), 10 (one patient), and 13 months (one patient). PDX is a new antifolate with manageable toxicity and evidence of antitumor activity in NSCLC. A Phase II trial in NSCLC and a Phase I trial with paclitaxel are under way. These studies will also quantitate the expression of genes controlling internalization (RFC-1) and polyglutamylation of PDX in tumor cells as correlates of response.  (+info)

Co-administration of probenecid, an inhibitor of a cMOAT/MRP-like plasma membrane ATPase, greatly enhanced the efficacy of a new 10-deazaaminopterin against human solid tumors in vivo. (8/155)

Earlier studies from this laboratory have shown that the uricosuric agent probenecid (PBCD) will inhibit the extrusion of folate analogues from tumor cells mediated by a plasma membrane ATPase resembling the canicular multispecific organic anion transporter/multidrug resistance-related protein (MRP) family of ATP binding cassette transporters. This inhibition of this outwardly directed membrane ATPase has been shown to have a favorable impact upon the cellular pharmacokinetics, cytotoxicity, and efficacy of methotrexate in vivo. In an extension of these earlier studies, which had focused only on murine ascites tumors, we now report that parental co-administration of PBCD will also enhance net intracellular accumulation in vitro and intracellular persistence in vivo of a new folate analogue, 10-propargyl-10-deazaaminopterin (PDX) in tumor cells. This resulted in marked enhancement of the efficacy of PDX against murine and human lung neoplasms and human prostate and mammary neoplasms growing as solid tumors in mice. As possible ATPases targeted by PBCD, all of these tumors expressed MRP-1, -4, and -7 genes, with expression of MRP-4 being greatest in each case. Four other MRP genes were expressed to a variable extent in some tumors but not others. The therapeutic enhancement of PDX by PBCD was manifested as tumor regression, where PDX alone was only growth inhibitory (A549 NSCL tumor), or as a substantial increase (3-4-fold) in overall regression and/or number of complete regressions (Lewis and LX-1 lung, PC-3 and TSU-PR1 prostate, and MX-1 mammary tumors) compared to PDX alone. Also, only in the case of PDX with PBCD, a significant number of mice transplanted with LX-1 or MX-1 tumors that experienced complete regression did not have regrowth of their tumor. In view of these results, clinical trials of this therapeutic modality appear to be warranted, especially in the case of new more efficacious folate analogues that are also permeants for this canicular multispecific organic anion transporter/MRP-like plasma membrane ATPase.  (+info)

Fetal aminopterin syndrome is a condition affecting babies whose mothers were exposed to the chemical aminopterin or methotraxate during pregnancy. Only about 50 cases have been reported. Babies exposed to aminopterin or methotraxate during development can be born with developmental delays such as inability to properly grow, abnormal arms or legs, and changes to the face or skull. Symptoms of fetal aminopterin syndrome depend on how early in pregnancy the woman is exposed to aminopterin or methotraxate and the dosage of the medication being used. There is no cure for fetal aminopterin syndrome, though symptoms can be managed. Aminopterin is no longer used, but methotraxate may still be used to treat some conditions such as cancer. Pregnant women should consult a physician before taking medications with either chemical ...
Aminopterin (4-Aminofolic acid), the 4-amino derivative of folic acid, is a folic acid antagonist. Aminopterin catalyses the reduction of folic acid to tetrahydrofolic acid, and competitively inhibits dihydrofolate reductase (DHFR) with a Ki of 3.7 pM. Aminopterin has anticancer and immunosuppressive activity. Aminopterin is used in treatment of pediatric leukemia. - Mechanism of Action & Protocol.
Aminopterin (4-aminopterojska kislina) je 4-amino derivat folne kisline, ki izkazuje imunosupresivno in citostatično delovanje. Aminopterin je sintezni derivat pterina. Deluje kot encimski zaviralec, ker se veže na vezišča encima dihidrofolat reduktaze (namesto fiziološkega substrata - folne kisline) in s tem zavre sintezo tetrahidrofolata. Posledično pride do motenj nastajanja nukleotidov in s tem do zaviranja sinteze DNK, RNK in beljakovin. Aminopterin se je nekoč uporabljal za zdravljenje raka, dandanes pa ga je povsem nadomestil metotreksat, ki je spojina s podobno strukturo. Ponekod se še vedno uporablja kot rodenticid. Leta 2007 se je v ZDA pojavil škandal z aminopterinom, ko so v okoli 100 vrst hrane za pse in mačke dokazali znatne količine spojine (nad 40 ppm). Hrano so umaknili iz prodaje. Aminopteridina pri živih živalih ni mogoče dokazati. Obstajajo sumi na nefrotoksično delovanje (strupen učinek na ledvice), vendar nedvomnih dokazov o njegovem delovanju na zdravje ...
Ovaj lek je otkrio Dr. Yellapragada Subbarao, a prvi je koristio njegovu antifolatnu aktivnost Sidni Farber 1947. da indukuje remisiju kod dece sa leukemijom.[3][4] Aminopterin je kasnije prodavala kompanija Lederle Laboratories (Pearl River, Njujork) u SAD od 1953 do 1964 za pedijatrijsku leukemiju. Ta kompanije je u toku istog perioda prodavala blisko srodni antifolat metotreksat. Lederle Laboratories je zatim obustavila prodaju aminopterina u korist metotreksata zbog proizvodnih razloga. Aminopterin je u toku svog tržišnog veka korišćen i za tretman psorijaze u SAD. Ovaj lek je doveo do dramatičnog čišćenja lezija.[5]. Upotreba aminopterina u tretmanu raka je zamenjena 1950-tih godina metotreksatom zbog boljeg terapeutskog indeksa metotreksata.[6] Nedavno je došlo do obnavljanja interesa u aminopterin, tako da su u toku klinička ispitivanja sa ciljom suzbijanja leukemije.[7]. Ovo jedinjenje je bilo istraženo kao abortifacijent 1960-tih i ranije, ali je bilo asocirano sa ...
Background: Relapsed/refractory Peripheral T-cell lymphomas (PTCL) is an aggressive and heterogeneous Non-Hodgkins T cell lymphoma, which is resistant to conve
Four folate analogues, methotrexate, aminopterin, 10-deazaaminopterin, and 10-ethyl-10-deazaaminopterin were assessed for their ability to be metabolized to poly-γ-glutamyl derivatives in three tumor lines which vary in their sensitivity to these agents. Cytotoxicity of the four analogues against the murine L1210 leukemia and the human Manca B cell leukemia, as determined by a 3-h clonogenic assay, showed aminopterin and the two 10-deazaaminopterin compounds to be approximately equivalent for each cell type and were 3- to 10- (L1210) and 7- to 14-fold (Manca) more potent than methotrexate. In murine Sarcoma 180 cells, 10-ethyl-10-deazaaminopterin and aminopterin were similarly potent but were 5- to 10-fold more potent than 10-deazaaminopterin and 40- to 80-fold more potent than methotrexate. These results could be explained in part by the differences in transport properties and substrate activities for polyglutamylation for each analogue in these cell types.. Initial rates of polyglutamate ...
Pralatrexate is given as an infusion into your vein over 3 to 5 minutes under the supervision of your doctor or nurse. Pralatrexate is usually given once a week for 6 weeks, with no treatment on the 7th week to complete the 7-week cycle. Several treatment cycles of pralatrexate may be given depending on your response to treatment. Prior to being given pralatrexate, your doctor will advise you to take certain medicines or vitamin supplements before starting and while being on treatment to help minimise side effects.. Pralatrexate is approved by the TGA for the following indication:. The treatment of adult patients with peripheral T-cell lymphoma (nodal, extranodal, and leukaemic/disseminated) who have progressed after at least one prior therapy.. Pralatrexate is listed on the PBS from April 1st, 2018. Breaking News. Pralatrexate may have the following side effects:. ...
Takeda Remains Committed to Continuing the Ongoing Alisertib Clinical Development Program Cambridge, MA, May 12, 2015 and Osaka, Japan, May 13, 2015 - Takeda Pharmaceutical Company Limited...
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. ...
PRIMARY OBJECTIVES:. I. To determine the overall response rate in patients with advanced esophago-gastric cancer (EGC) to combination pralatrexate and oxaliplatin.. SECONDARY OBJECTIVES:. I. To examine the toxicity and tolerability of this regimen. II. To determine the time-to-progression and overall survival using this regimen.. III. To examine whether functionally relevant polymorphisms of genes of the folate metabolism pathway correlate with efficacy and toxicity of pralatrexate.. IV. To examine whether response to pralatrexate can be predicted by micro-ribonucleic acid (microRNA) expression profiling of the epithelial component of the tumor.. OUTLINE:. Patients receive pralatrexate intravenously (IV) over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses.. After completion of study treatment, patients are followed up for 30 days and then ...
...NCCN has added pralatrexate (Folotyn(TM) Allos Therapeutics Inc.) to...FORT WASHINGTON Pa. Oct. 15 -- Upon the rece...The updated NCCN Guidelines have added pralatrexate as a second-line t...Peripheral T-cell lymphoma is a rare form of non-Hodgkins lymphoma th...,NCCN,Updates,NHL,Guidelines,Following,FDA,Approval,of,Pralatrexate,medicine,advanced medical technology,medical laboratory technology,medical device technology,latest medical technology,Health
In the current study we addressed the question as to whether membrane translocation in the overall process of FGF-2 externalization requires protein unfolding. For this purpose we combined a FACS-based in vivo system reconstituting FGF-2 export (Engling et al., 2002) with a modified FGF-2-GFP reporter molecule that contains the DHFR domain at its C-terminus. The membrane-permeable folate analogue aminopterin (Eilers and Schatz, 1986; Wienhues et al., 1991) was used to stabilize the DHFR domain in vivo, which allows us to analyse a potential need for protein unfolding during FGF-2 export. The principal finding of this study is that membrane translocation of FGF-2 by living cells apparently occurs in a folded conformation as an FGF-2-GFP-DHFR fusion protein is efficiently exported in the presence of aminopterin. Importantly, on the basis of antibodies directed against the N-terminal part (anti-GFP) of the reporter, as well as antibodies directed against the extreme C-terminus (anti-His), we showed ...
In June 3, 1948, The New England Journal of Medicine published a study by Sidney Farber, MD, showing that a synthetic compound, 4-aminopteroylglutamic acid (aminopterin), could induce remissions in seriously ill children with acute leukemia.1 Although the study was small-just 16 children-10 showed clinical, hematologic, and pathologic evidence of improvement. Even though the childrens remissions were short-lived, Dr. Farbers findings were so groundbreaking-until then, no drug had proved effective against non-solid tumor cancers-they ushered in the era of chemotherapeutics, chemical agents that could stop cancer cells from growing and replicating, in effect killing them.. Aminopterin was later replaced by methotrexate, a similar but more effective folic acid antagonist with fewer side effects, which is still used today in the treatment of leukemia and other blood and solid tumor cancers. Nevertheless, the results of Dr. Farbers study earned him the title, the Father of Modern ...
days in Clicks medium with 0.5% NMS and then placed in IL-2 for 3 days to expand. T cell clones and lines can be successfully fused following an analogous schedule, in this case the clone or line is set up in a standard re-stimulation flask with 5.0 X 105 T cells, 2.0 X 107 irradiated NOD spleen cells in 20 ml DMEM/10% FBS with 50U/ml IL-2. The cultures are incubated for four days at which point they are subjected to Lympholyte M separation and culture for 3 days in 50 U/ml IL-2, the cells are then counted and washed as below.. Hybrid cells are selected by culturing the fused cells in hypoxanthine/aminopterin/thymidine (HAT). The aminopterin component of HAT inhibits a key enzyme in purine and ...
Within the last decade, weve witnessed the emergence from the oral non-vitamin K oral anticoagulants (NOACs), that have numerous advantages weighed against the vitamin K antagonists, particularly their insufficient dependence on monitoring; because of this their use is definitely increasing. checks, thromboelastometry guidelines buy Aminopterin and thrombin-generation indices induced by rivaroxaban and apixaban.34 Antifibrinolytic Providers. Tranexamic acidity inhibits fibrinolysis therefore stabilisng fibrin clots. Nevertheless, its prothrombic potential in NOAC-associated blood loss is unfamiliar. buy Aminopterin Haemodialysis. Dabigatran could be taken off the blood flow by haemodialysis in individuals with major blood loss or surgical treatments. This approach requires 4C6 hours, and it is more appealing in individuals with end-stage renal disease and overdosing.46 Expert Opinion: What Should We Make use of?23,34 Its important to check out the exact period of last NOAC intake. Predicated ...
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Term] id: EDAM:0002078 name: Sequence range format namespace: format def: Format used to specify range(s) of sequence positions. subset: format is_a: EDAM:0002350 ! Format (typed) relationship: is_format_of EDAM:0001017 ! Sequence range [Term] id: EDAM:0002571 name: Raw sequence format namespace: format def: Format of a raw molecular sequence (i.e. the alphabet used). subset: format is_a: EDAM:0002350 ! Format (typed) relationship: is_format_of EDAM:0000848 ! Raw sequence [Term] id: EDAM:0001921 name: Alignment format namespace: format def: Data format for molecular sequence alignment information. subset: format is_a: EDAM:0002350 ! Format (typed) relationship: is_format_of EDAM:0000863 ! Sequence alignment [Term] id: EDAM:0001919 name: Sequence record format namespace: format def: Data format for a molecular sequence record. subset: format is_a: EDAM:0002350 ! Format (typed) relationship: is_format_of EDAM:0000849 ! Sequence record [Term] id: EDAM:0002057 name: Sequence trace format namespace: ...
This phase II trial evaluated the efficacy of pralatrexate plus oxaliplatin in the treatment of patients with unresectable or metastatic oesophageal, stomach,
FOLOTYN (Pralatrexate) drug information & product resources from MPR including dosage information, educational materials, & patient assistance.
On Friday, the U.S. Food and Drug Administration said recalled pet foods contained melamine, a chemical used to make plastics, but that its tests failed to confirm the presence of a rat poison, aminopterin, reported by the New York State Food Laboratory. The FDA said it also found melamine in wheat gluten used as an ingredient in the wet-style products. Still, it was not immediately clear whether the melamine was the culprit in the deaths.. ...
In March 2007, the most lethal pet food in history was the subject of the largest recall ever. Menu Foods recalled more than 100 brands including Iams, Eukanuba, Hills Science Diet, Purina Mighty Dog, and many store brands including Wal-Marts. Thousands of pets were sickened (the FDA received more than 17,000 reports) and an estimated 20% died from acute renal failure caused by the food. Cats were more frequently and more severely affected than dogs. The toxin was initially believed to be a pesticide, the rat poison aminopterin in one of the ingredients. In April, scientists discovered high levels of melamine, a chemical used in plastics and fertilizers, in wheat gluten and rice protein concentrate imported from China. The melamine had been purposefully added to the ingredients to falsely boost their protein content. Subsequent tests revealed that the melamine-tainted ingredients had also been used in feed for cows, pigs, and chickens and thousands of animals were quarantined and destroyed. ...
Term] id: EDAM:0000850 name: Sequence set namespace: data def: A collection of multiple molecular sequences and associated metadata that do not (typically) correspond to molecular sequence database records or entries and which (typically) are derived from some analytical method. [EDAM:EBI EMBRACE definition] comment: This term may be used for arbitrary sequence sets and associated data arising from processing. subset: data is_a: EDAM:0002955 ! Sequence report [Term] id: EDAM:0001234 name: Sequence set (nucleic acid) namespace: data def: Any collection of multiple nucleotide sequences and associated metadata that do not (typically) correspond to common sequence database records or database entries. [EDAM:EBI EMBRACE definition] subset: data is_a: EDAM:0000850 ! Sequence set is_a: EDAM:0002977 ! Nucleic acid sequence [Term] id: EDAM:0001240 name: PCR primers namespace: data def: Oligonucleotide primer(s) for PCR and DNA amplification, for example a minimal primer set. [EDAM:EBI EMBRACE ...
The goal of this clinical research study is to learn if it is safe to give pembrolizumab in combination with romidepsin to patients with peripheral T-cell
Term] id: EDAM:0000850 name: Sequence set namespace: data def: A collection of multiple molecular sequences and associated metadata that do not (typically) correspond to molecular sequence database records or entries and which (typically) are derived from some analytical method. comment: This term may be used for arbitrary sequence sets and associated data arising from processing. subset: data is_a: EDAM:0002955 ! Sequence report [Term] id: EDAM:0001234 name: Sequence set (nucleic acid) namespace: data def: Any collection of multiple nucleotide sequences and associated metadata that do not (typically) correspond to common sequence database records or database entries. subset: data is_a: EDAM:0000850 ! Sequence set is_a: EDAM:0002977 ! Nucleic acid sequence [Term] id: EDAM:0001240 name: PCR primers namespace: data def: Oligonucleotide primer(s) for PCR and DNA amplification, for example a minimal primer set. subset: data is_a: EDAM:0001234 ! Sequence set (nucleic acid) [Term] id: EDAM:0001246 ...
Several HDAC inhibitors have been studied in clinical trials for non-Hodgkin lymphoma. However, only three HDAC inhibitors (romidepsin, vorinostat and belinostat) have received approval. Vorinostat was granted regular approval for third-line cutaneous T-cell lymphoma based on two open-label trials (one was a single-arm trial and the other assessed several dosing regimens) achieving ORRs of 30% (median DoR was not reached but estimated to exceed 6 months) and 24% (median DoR of 106 days).. The accelerated approval of belinostat was based on efficacy and safety data from a single-arm phase II trial. With the approval of belinostat, three drugs are now approved for the treatment of relapsed or refractory PTCL under the accelerated approval regulations: pralatrexate in 2009, romidepsin in 2011, and belinostat in 2014. Although cross-study comparisons must be interpreted with caution, the ORRs were similar for the three drugs: belinostat (ORR: 26%, CR: 11%, DoR: 8.4 months), pralatrexate [ORR: 27%, ...
Online lymphoma resource for healthcare professionals, providing information, news & support relating to lymphoma, Hodgkin & non Hodgkin disease
This drug may make you feel generally unwell. This is not uncommon, as chemotherapy can affect healthy cells as well as cancer cells. Report any side effects. Continue your course of treatment even though you feel ill unless your doctor tells you to stop.. Call your doctor or health care professional for advice if you get a fever, chills or sore throat, or other symptoms of a cold or flu. Do not treat yourself. This drug decreases your bodys ability to fight infections. Try to avoid being around people who are sick.. This medicine may increase your risk to bruise or bleed. Call your doctor or health care professional if you notice any unusual bleeding.. Do not become pregnant while taking this medicine or for 6 months after the last dose. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child. Men should not father a child while taking this medicine or for 3 months after the last dose. ...
Well, you didnt, did you? Nalgol bit out, thoroughly disgusted. First the strike team, now Oissan. Get back to work. We still have an hour or two before the battle out there winds down to where well be entering it. VOTF p.651. In other words, Han Solo figured that a single Star Destroyer could finish off the warring fleets by itself and then burn off Bothawui, all with no survivors, no witnesses, and Nalgol confirmed this plan. The three ISDs were just insurance; it is quite obvious from Solos interpretation of the plan that its common knowledge in the New Republic that a single Star Destroyer is capable of doing this on its own. Enough of your lies and evasions, Edam. Stand up and debate like a man.. Or it is common misinformation. Everytime we see ISDs and similar ships try to do this they take hours to do it - the whole operation with 10x the capacity for damage is expected to take hours. 100 VSDs attacking Khomm did very little damage in half an hour. When Boosters ISD slagged the ...
Learn about the potential side effects of Folotyn (pralatrexate). Includes common and rare side effects information for consumers and healthcare professionals.
Looking for online definition of pralatrexate in the Medical Dictionary? pralatrexate explanation free. What is pralatrexate? Meaning of pralatrexate medical term. What does pralatrexate mean?
Copyright:www.vvchem.com 2010-2020 source chemicals on the most professional electronic B2B platform ICP NO.:浙ICP备09052245号-11 ...
We present a retrospective multicenter study of pralatrexate treatment outcomes in an Australian practice setting for patients with relapsed/refractor
RATIONALE: Pralatrexate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as f
Four staphylococcal substrains resistant to sulphonamides were developed from sensitive parent strains by subcultivation in increasing concentrations of sulphathiazole. As compared with the parent strains, the growth of the resistant strains was 20-200-fold less sensitive to sulphathiazole in a semi-defined medium based on acid hydrolyzed casein than were the parent strains. Inhibition of growth by sulphathiazole was overcome competitively by p-aminobenzoic acid. The inhibition indices of the sulphathiazole-sensitive strains were about 10, and [email protected] for the resistant substrains; the change in index was about proportional to the degree of resistance. The sulphathiazole-resistant strains were cross-resistant to other sulphonamides but were not resistant to p-nitrobenzoic acid. Not one of the sensitive or resistant strains was inhibited by aminopterin. No change in the inhibitory effect of sulphathiazole occurred during growth of cultures in its presence, though the drug was partly converted to a second
Chemotherapeutic agents: Chemotherapy, Pawpaw, Biosynthesis of doxorubicin, Camptothecin, Epothilone, Aminopterin, ABVD, Cyclophosphamide von Source: Wikipedia bei AbeBooks.de - ISBN 10: 1157367399 - ISBN 13: 9781157367390 - Books LLC, Wiki Series - 2011 - Softcover
Chemotherapy of malaria parasites is bound by established medication absence and level of resistance of book focuses on. and demonstrate inhibition of blood sugar uptake Tozadenant from the lengthy chain inside a mouse model can be significantly reduced from the oocyte malaria antimalarial blood sugar analogues transport Disease with causes malaria which kills 1 million kids and afflicts an additional 400 million people each year. New medicines are urgently had a need to deal with malaria because regular cheap treatment plans are compromised by medication level of resistance. Parasite Tozadenant membrane transportation proteins never have yet been positively exploited as medication focuses on (1). Asexual stage parasites need a continuous way to obtain blood sugar to survive and multiply (2) recommending how the hexose transporter (PfHT) of can be a potential medication target (3). Huge increases in blood sugar utilization by contaminated erythrocytes could also divert this important substrate ...
During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market. ...
A Dutch import made with part-skim cows milk for a rich, buttery flavor with a hint of sweetness, this cheese has a smooth, firm texture. Boars Head® Edam Cheese is inspired by cheese-making traditions that originated in Holland more than eight centuries ago.
Cheese, edam Nutrition - BellaOnline Nutrition Database - BellaOnline is committed to helping our visitors become healthy and happy. Our BellaOnline Nutrition Database will help you choose the healthiest foods for your chosen lifestyle.
Shop Primo Taglio Cheese Aged Gouda - 0.5 Lb from Randalls. Browse our wide selection of Gouda & Edam Cheese for Delivery or Drive Up & Go to pick up at the store!
The Department comprises a number of disciplines from the study of the earliest civilizations to the philosophy of the mind, from world literature to the study of comparative mythology and great religions of the world, from the beginning of theatre in ancient Greece to the latest Broadway plays and Hollywood movies, from music through the ages to the appreciation of art ...
Purpose: Pralatrexate is a folic acid analogue metabolic inhibitor similar to methotrexate, which has shown tolerability and efficacy with an overall response rate of 45% in a phase I dose deescalation study of patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL).. Experimental Design: The object of this phase I/II open-label, multicenter clinical trial was to determine the MTD and recommended dose of pralatrexate plus oral bexarotene in 34 patients with relapsed/refractory CTCL who had failed prior systemic therapies. Pralatrexate was administered by intravenous push at 15 mg/m2 given weekly 3 weeks out of 4 weeks with daily oral bexarotene (150 or 300 mg/m2), levothyroxine, atorvastatin, folate, and with B12 every 2 months.. Results: At the MTD of 15 mg/m2 bexarotene and 15 mg/m2 pralatrexate, the response rate was 60% [4 complete responses (CR), 14 partial responses (PR)], the maximum observed response duration was 28.9+ months, and duration of response for 4 CRs ranged from 9.0 ...
Purpose The positron-emitting tomography (PET) tracer, 124I-cG250, directed against carbonic anhydrase IX (CAIX) shows promise for pre-surgical analysis of very clear renal cell carcinoma (cRCC) [1, 2]. two tracers endocytosis, 124I-iodotyrosine is expelled through the cell after lysosomal degradation [7] rapidly. Conversely, residualizing radiometals such as for example 111In and 177Lu are maintained from the cell by means of low-molecular pounds catabolites [8]. This trend has been proven to possess clinical outcomes for cG250/CAIX imaging; for instance, Brouwers, performed a primary intra-patient assessment of single-photon Pralatrexate emission computed tomography imaging of 131I-cG250 and 111In-cG250 in RCC metastases and discovered that the total amount of lesions exposed was greater using the 111In-labeled tracer, because of the higher activity in the lesions and the bigger tumor-to-blood ratios [9] general. The longer-lived radiometal 89Zr offers emerged as a good option to 124I, due to ...
Pralatrexate (PDX, 10-propargyl 10-deazaaminopterin) is a novel anti-folate agent that is approved for use in relapsed peripheral T cell lymphoma (PTCL). It is distinguished from the parent drug methotrexate (MTX) by having significantly greater affinity for the reduced folate carrier (RFC)-1, the principle transporter that internalize anti-folates, as well as broader efficacy, which strongly suggests that PDX has mechanisms of action beyond inhibition of nucleotide synthesis. Given the activity of PDX in aggressive lymphoid malignancies such as PTCL, we examined the activity of this agent in preclinical models of multiple myeloma (MM), a plasma cell malignancy that is currently incurable. We examined the cytotoxic activity of anti-folates in vitro against a panel of human multiple myeloma cell lines (HMCL) and showed that PDX induced dose-dependent apoptotic cell death in a subset of these. In sensitive cell lines (MM.1s and ARH-77) PDX demonstrated significantly greater potency at 48 hours ...
Sterigmatocystin (STG), a biosynthesis precursor of aflatoxin B1, is well known for its toxic and carcinogenic effects in humans and animals. STG derivatives and protein conjugates are needed for generation of monoclonal antibodies (mAbs). This work describes a reliable and fast synthesis of novel STG derivatives, based on which novel STG bovine serum albumin conjugates were prepared. With the novel STG bovine serum albumin conjugates, three sensitive and specific mAbs against STG, named VerA 3, VerA 4, and VerA 6, were prepared by semi-solid hypoxanthine/aminopterin/thymidine (HAT) medium using a modified two-step screening procedure. They exhibited high affinity for STG and no cross-reactivity (CR) with aflatoxins B1, B2, G1, G2, and M1. Based on the most sensitive antibody VerA 3, an ultra-sensitive competitive enzyme-linked immunosorbent assay (ELISA) was developed for STG in wheat, maize, and peanuts. Assays were performed in the STG-GA-BSA-coated (0.5 g mL(-1)) ELISA format, in which the ...
Find public databases by data type Version: EMBOSS:6.5.0.0 Standard (Mandatory) qualifiers: [-query] string List of EDAM data keywords (Any string) [-outfile] outresource [*.drfinddata] Output data resource file name Additional (Optional) qualifiers: (none) Advanced (Unprompted) qualifiers: -sensitive boolean [N] By default, the query keywords are matched against the EDAM term names (and synonyms) only. This option also matches the keywords against the EDAM term definitions and will therefore (typically) report more matches. -[no]subclasses boolean [Y] Extend the query matches to include all terms which are specialisations (EDAM sub-classes) of the matched type. Associated qualifiers: -outfile associated qualifiers -odirectory2 string Output directory -oformat2 string Data resource output format General qualifiers: -auto boolean Turn off prompts -stdout boolean Write first file to standard output -filter boolean Read first file from standard input, write first file to standard output -options ...
DBL Calcium Folinate is a medicine available in a number of countries worldwide. A list of US medications equivalent to DBL Calcium Folinate is available on the Drugs.com website.
The code doesnt appear to be conforming to RFC-3164 or RFC-5424: (From RFC-3164): 4.1 syslog Message Parts The full format of a syslog message seen on the wire has three discernable parts. The first part is called the PRI, the second part is the HEADER, and the third part is the MSG. The total length of the packet MUST be 1024 bytes or less. There is no minimum length of the syslog message although sending a syslog packet with no contents is worthless and SHOULD NOT be transmitted. (From RFC-5424) The reason syslog transport receivers need only support receiving up to and including 480 octets has, among other things, to do with difficult delivery problems in a broken network. Syslog messages may use a UDP transport mapping with this 480 octet restriction to avoid session overhead and message fragmentation. In a network with problems, the likelihood of getting one single-packet message delivered successfully is higher than getting two message fragments delivered successfully. Therefore, using a ...
milk, table salt, dairy cultures the list of ingredients is not indicated on the packaging, see Article 19, paragraph 1, point d, EU Regulation No. 1169/2011 ...
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... has a single-dose LDLo of 2.5 mg/kg when orally administered to rats. Aminopterin is widely used in selection media ... Aminopterin is a synthetic derivative of pterin. Aminopterin works as an enzyme inhibitor by competing for the folate binding ... and 0.097 mg/kg aminopterin each day for 7 to 12 days. Folic acid was given in a weight ratio to aminopterin of 200:1 to 800:1 ... the enzyme inhibited by aminopterin. Leucovorin has been used in rats, dogs and humans to rescue aminopterin toxicity. ...
"Aminopterin". PubChem. U.S. National Library of Medicine. Köhler G, Milstein C (August 1975). "Continuous cultures of fused ... After fusion, the cells are grown in a medium with methotrexate or aminopterin that inhibit the enzyme dihydrofolate reductase ... One such medium that is commonly used is HAT medium, which contains hypoxanthine, aminopterin and thymidine. The unfused cells ...
Osborn, M. J.; Freeman, M.; Huennekens, F. M. (February 1958). "Inhibition of dihydrofolic reductase by aminopterin and ... Inhibition of Dihydrofolic Reductase by Aminopterin and Amethopterin. DOI: 10.3181/00379727-97-23764 Wayne, Tiffany K. (2011 ...
... hypoxanthine-aminopterin-thymidine medium) for roughly 10 to 14 days. Aminopterin blocks the pathway that allows for nucleotide ...
Aminopterin in the medium blocks the de novo pathway. Hence, unfused myeloma cells die, as they cannot produce nucleotides by ... HAT Medium (hypoxanthine-aminopterin-thymidine medium) is a selection medium for mammalian cell culture, which relies on the ... The trick is that aminopterin blocks DNA de novo synthesis, which is absolutely required for cell division to proceed, but ... is specifically blocked by aminopterin. THF, acting in association with specific proteins, can receive single carbon units that ...
Aminopterin is illegal in China, and neither Cornell University nor the FDA could replicate the New York lab's results. On 27 ... "No Aminopterin in Tissues of Animals Killed by Recalled Pet Food". PRNewsWire. March 30, 2007. Archived from the original on ... On 23 March, the New York State Food Laboratory reported that aminopterin was found in samples sent to them by Cornell. ... Beginning on 19 April, researchers reportedly had ruled out aminopterin contamination and had found a "spoke-like crystal" in ...
The New York State Food Laboratory reported that aminopterin was found in samples sent to them by Cornell. Aminopterin is ... "No Aminopterin in Tissues of Animals Killed by Recalled Pet Food" (Press release). Syntrix Biosystems. March 30, 2007. Archived ... "fully consistent with the ingestion of rat poison containing aminopterin." The U.S. Food and Drug Administration (FDA) ...
He obtained his Ph.D. the same year, and went on to make other major discoveries; including the synthesis of aminopterin (later ...
This medium is supplemented with hypoxanthine, aminopterin and thymidine, hence the name HAT medium. Antimetabolite aminopterin ... since they cannot produce purines and pyrimidines due to the aminopterin present in the HAT medium). For using HAT medium as a ...
Exposing cells to aminopterin (a folic acid analogue, which inhibits dihydrofolate reductase, DHFR), makes them unable to use ... The selective culture medium is called HAT medium because it contains hypoxanthine, aminopterin and thymidine. This medium is ...
Effect of folic acid, aminopterin and vitamin K on growth of roots in Allium cepa. Proc. Soc. Exp. Biol. Med. 74:310-12 "The ...
These analogues - first aminopterin and then amethopterin (now methotrexate) were antagonistic to folic acid, and blocked the ... and similar to aminopterin) treatment. Dr. Richard Lewisohn of Mount Sinai Hospital in New York administered the drug, and over ... Aminopterin)". New England Journal of Medicine. 238 (23): 787-793. doi:10.1056/nejm194806032382301. PMID 18860765. Retrieved ...
... aminopterin)". N. Engl. J. Med. 238 (23): 787-93. doi:10.1056/NEJM194806032382301. PMID 18860765.{{cite journal}}: CS1 maint: ...
Realizing this, he attempted to use a folate antagonist, aminopterin, to block the function of folic acid in patients with ... In 1947, Farber conducted a clinical trial on aminopterin on 16 children, 10 of which eventually achieved temporary remission. ... aminopterin)". New England Journal of Medicine. 238 (23): 787-793. doi:10.1056/nejm194806032382301. PMID 18860765.{{cite ... he carried out both the preclinical and clinical evaluation of aminopterin (synthesized by Yellapragada Subbarow). He showed ...
Aminopterin, a cytostatic drug with antifolate effect, was used during the 1950s and 1960s to induce therapeutic abortions. In ... some cases, the abortion did not happen, but the newborns had a fetal aminopterin syndrome consisting of growth retardation, ...
Often the de novo pathway is interrupted as a result of chemotherapy drugs such as methotrexate or aminopterin. All salvage ...
His team gave 16 infants and children with acute lymphoblastic leukemia a folic acid inhibitor, aminopterin-10 showed ... Aminopterin)". New England Journal of Medicine. 238 (23): 787-93. doi:10.1056/NEJM194806032382301. PMID 18860765. Zoll, PM ( ...
Farber was able to use a drug of this type, aminopterin, to achieve a temporary remission in childhood leukemia. In the early ...
... experimenting with the impact of aminopterin on leukemia. Pinkel was named chief of pediatrics at Roswell Park Comprehensive ...
By 1947, Boston pathologist Sidney Farber believed from past experiments that aminopterin, a folic acid mimic, could ...
This research subsequently led to the synthesis of the antifolate aminopterin, which was used to treat childhood leukemia by ...
In 1947, a team of researchers led by Sidney Farber showed aminopterin, a chemical analogue of folic acid developed by ... Animal studies published in 1956 showed the therapeutic index of methotrexate was better than that of aminopterin, and clinical ... use of aminopterin was thus abandoned in favor of methotrexate. In 1951, Jane C. Wright demonstrated the use of methotrexate in ...
In particular, the group found that L1210 sublines that were resistant to the folate analogue aminopterin (later replaced by ...
... aminopterin MeSH D03.438.733.631.192.500 - methotrexate MeSH D03.438.733.631.202 - biopterin MeSH D03.438.733.631.202.500 - ...
Yellapragada Subbarow (of Lederle lab and his friend and colleague at Harvard Medical School) to supply Aminopterin and later ... Sidney Farber received the Lasker in 1966 for his 1947 discovery that a combination of aminopterin and methotrexate, both folic ...
... using aminopterin. This, and another antifolate drug, methotrexate used by Dr. Farber, were discovered and supplied by Dr. ...
Some of the known developmental toxicants can be grouped under the following categories: Reproductive toxins: Aminopterin ...
... known for the synthesis of the first ever chemotherapeutic drug aminopterin, and subsequently methotrexate. He is also known ...
David Galton became the first physician in the world to use aminopterin (the forerunner of the methotrexate drug) in the ...
... aminopterin, melamine (a plastic precursor that may also be used as a fertiliser), and cyanuric acid (which is commonly used to ...
... aminopterin , aminopterine , aminopterin sodium , a-ninopterin , apga , minopterin , n-(4-{[(2,4-diamino-6-pteridinyl)methyl] ... During the period Aminopterin was marketed, the agent was used off-label to safely treat over 4,000 patients with psoriasis in ... The use of aminopterin in cancer treatment was supplanted in the 1950s by methotrexate due to the latters better therapeutic ... Aminopterin was marketed by Lederle Laboratories (Pearl River, New York) in the United States from 1953 to 1964 for the ...
Folic acid is a type of B vitamin. This article discusses the test to measure the amount of folic acid in the blood.
The use of methotrexate, aminopterin, or folinic acid (leucovorin) If testing is not being performed immediately, specimens may ...
By late January, aminopterin had brought the childs WBC count down to the realm of 12,000, just slightly above normal, with ... Testing aminopterin, beginning with young Robert Sandler at the end of December, is what proved his hypothesis correct. ... As early as the 1950s, dermatologists were using aminopterin to treat psoriasis. This led to the approval of methotrexate for ... Merely another chemical modification in a series of attempts by the research team, the new drug, aminopterin, was not expected ...
Aminopterin 3. Trimethoprim [USAN:USP:INN:BAN:JAN] 4. Pyrimethamine [USP:INN:BAN:JAN] ...
... aminopterin, and thymidine (HAT medium), which substances prevent the growth of HGPRT-deficient cells. ... aminopterin; xeloda; ibandronate; CPT-11; topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoic acid; ...
teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; CPT-11; topoisomerase inhibitor RFS 2000; ...
AMINOPTERIN AND ITS SALTS. 4-AMINO-PTEROYL ASPARTIC ACID. AND ITS SALTS. AMINOPYRINE AND ITS DERIVATIVES. AMITRIPTYLINE AND ITS ...
TCI uses cookies to personalize and improve your user experience. By continuing on our website, you accept the use of cookies. You can change or update your cookiesettings at any time.. ...
Aminopterin - 54-62-6 - Toxicity: developmental, female. *Amiodarone hydrochloride - 19774-82-4 - Toxicity: developmental, ...
CHO cells were cleansed in medium supplemented with hypoxanthine, aminopterin and thymidine (HAT) then frozen. The freeze lot ... CHO cells were cleansed in medium supplemented with hypoxanthine, aminopterin and thymidine (HAT) then frozen. The freeze lot ...
ATTENTION : Tous les résultats de la recherche seront tirés du « National Drug Schedules » du site Web en anglais.
These media do not contain hypoxanthine, aminopterin, thymidine, glutamine, or any other selective agents or antibiotics. These ...
Hypoxanthine, aminopterin, thymidine. ELISA:. Enzyme-linked immunosorbent assay. VH:. Heavy chain variable region ...
Menu Foods initially blamed the contamination on a chemical called Aminopterin, which is used as a rat poison and to treat ...
Sydney Farber and colleagues reported successfully treating acute leukemia in children with a new drug called aminopterin. By ...
Pretreatment medium ("HAT" medium): Hams F12 medium with hypoxanthine (136 µg/mL), aminopterin (1.8 µg/mL), thymidine (38.8 µg ...
Splenocytes were fused with P3U1 cells and hypoxanthine-aminopterin-thymidine selection was performed. The monoclonal antibody ...
The first step is transferring of the cell fusion mixture to HAT culture medium which contains hypoxanthine, aminopterin & ... pathway that they synthesize purines so lack of HGPRT is not a problem for the cell but when cells are exposed to aminopterin ...
The aminopterin found in the medium blocks the de novo DNA nucleotide synthesis pathway. ... in animal cell culture medium and plasma cells contribute the functional HGPRT enzyme necessary to overcome the aminopterin ...
Yellapragada Subbarao, the then Director of the institute, was the basis for synthesis of Aminopterin, the first ever anti- ...
Poisonous chemicals such as "melamine," "aminopterin," and "cyanuric acid" were identified in pet food products imported from ...
A pharmaceutical company had synthesized this "antagonist" to folic acid (aminopterin), and in November 1947, Farber tried the ...
... aminopterin (APN) and mitomycin C (MC). All of the test agents are mammalian developmental toxicants and/or teratogens. One-to- ...
Aminopterin D3.438.733.631.192 D3.633.100.733.631.192 Aminoquinolines D3.438.810.50 D3.633.100.810.50 Amiodarone D3.438.127.75 ...
Theres someone else to sue. Class action lawsuits are already being filed against MF, but the toxic chemical aminopterin (used ...
Aminopterin. Aminopterin (or 4-aminopteroic acid), the 4-amino derivative of folic acid, is an antineoplastic drug with ... New!!: The New England Journal of Medicine and Aminopterin · See more ». Amputation. Amputation is the removal of a limb by ... 63 relations: Acute lymphoblastic leukemia, Addiction Rare in Patients Treated with Narcotics, Aminopterin, Amputation, ...
  • Aminopterin was discontinued by Lederle Laboratories in favor of methotrexate due to manufacturing difficulties of the former. (liu.edu)
  • The use of aminopterin in cancer treatment was supplanted in the 1950s by methotrexate due to the latter's better therapeutic index in a rodent tumor model. (liu.edu)
  • Now in a more pure preparation and supported by laboratory evidence of superior tumor cell uptake in vitro, aminopterin is being investigated in clinical trials in leukemia as a potentially superior antifolate to methotrexate. (liu.edu)
  • To further characterize the Drosophila-based prescreen to detect developmental toxicants, the following 8 chemicals were evaluated - methyl mercury chloride (MMC), methotrexate (MTX), L-phenylalanine (LPA), sodium arsenate heptahydrate (SAH), cadmium chloride (CC), vinblastine sulfate (VBS), aminopterin (APN) and mitomycin C (MC). (cdc.gov)
  • Congenital cardiac defects: a possible association of aminopterin syndrome and in utero methotrexate exposure? (cdc.gov)
  • Splenocytes were fused with P3U1 cells and hypoxanthine-aminopterin-thymidine selection was performed. (leinco.com)
  • HAT selective medium components ( hypoxanthine, aminopterin, thymidine) are used. (modernloveok.com)
  • however, contributing factors include folic acid deficiency, anticonvulsant therapy with carbamazepine and valproic acid, antineoplastic drug therapy with aminopterin or other folic acid antagonists, antimalarial drugs, and maternal diabetes (Hansen & Warf, 2017). (nann.org)
  • An earlier suspect toxin was aminopterin, an antagonist of folic acid. (petplace.com)
  • A pharmaceutical company had synthesized this "antagonist" to folic acid (aminopterin), and in November 1947, Farber tried the drug on 16 terminally ill children. (massmoments.org)
  • The aminopterin, maternal diabetes, hyperther- hospital serves as a referral centre for ob- mia, low socioeconomic status, and lack of stetric and gynaecologic problems and a folate have been shown to increase the risk prenatal intensive care unit for all other of NTD. (who.int)
  • Transformative therapies have come before, with a broad spectrum of activity and durable response (eg, chemotherapies like aminopterin or cisplatin, the B-cell-targeting rituximab, among many others). (cldinc.com)
  • In the late 1940s, legendary cancer researcher Sydney Farber and colleagues reported successfully treating acute leukemia in children with a new drug called aminopterin. (statnews.com)
  • Poisonous chemicals such as "melamine," "aminopterin," and "cyanuric acid" were identified in pet food products imported from China. (kennesaw.edu)
  • Aminopterin (or 4-aminopteroic acid), the 4-amino derivative of folic acid, is an antineoplastic drug with immunosuppressive properties often used in chemotherapy. (unionpedia.org)
  • Aminopterin is a synthetic derivative of pterins with antineoplastic and immunosuppressive properties. (liu.edu)
  • As a folate analog, aminopterin competes for the folate binding site of the enzyme dihydrofolate reductase, thereby blocking tetrahydrofolate synthesis, and resulting in depletion of nucleotide precursors and inhibition of DNA, RNA and protein synthesis. (liu.edu)
  • The aminopterin found in the medium blocks the de novo DNA nucleotide synthesis pathway. (turningtooneanother.net)
  • This research in the Lederley Lab, Pearl River, NY under Dr. Yellapragada Subbarao, the then Director of the institute, was the basis for synthesis of Aminopterin, the first ever anti-cancer drug, the clinical proof of its efficacy was proven by Dr. S. Farber in 1948. (news-medical.net)
  • medium, since the myeloma cells provide the ability to grow in animal cell culture medium and plasma cells contribute the functional HGPRT enzyme necessary to overcome the aminopterin blocks. (turningtooneanother.net)
  • Incubation of fused cells in the HAT medium cause aminopterin in the myeloma cells death as nucleotide inhibition occur. (modernloveok.com)
  • Menu Foods initially blamed the contamination on a chemical called Aminopterin, which is used as a rat poison and to treat cancer. (dogster.com)
  • Director Daniel Rice said aminopterin was a cancer drug about 50 years ago in the United States. (petplace.com)
  • The New York State Food Laboratory reported that it found aminopterin in food from the palatability studies. (petplace.com)
  • At press time, no laboratory had announced an independent confirmation of the aminopterin finding. (petplace.com)
  • Tous les résultats de la recherche seront tirés du « National Drug Schedules » du site Web en anglais. (napra.ca)
  • Analogues of methotrexate and aminopterin with gamma-methylene and gamma-cyano substitution of the glutamate side chain: synthesis and in vitro biological activity. (harvard.edu)
  • Aminopterin and methotrexate, which have a structure similar to that of folic acid, are used in the treatment of certain types of malignant tumors. (thefreedictionary.com)
  • To further characterize the Drosophila-based prescreen to detect developmental toxicants, the following 8 chemicals were evaluated - methyl mercury chloride (MMC), methotrexate (MTX), L-phenylalanine (LPA), sodium arsenate heptahydrate (SAH), cadmium chloride (CC), vinblastine sulfate (VBS), aminopterin (APN) and mitomycin C (MC). (cdc.gov)
  • Aminopterin was discontinued by Lederle Laboratories in favor of methotrexate due to manufacturing difficulties of the former. (cloudfront.net)
  • The use of aminopterin in cancer treatment was supplanted in the 1950s by methotrexate due to the latter's better therapeutic index in a rodent tumor model. (cloudfront.net)
  • [5] Now in a more pure preparation and supported by laboratory evidence of superior tumor cell uptake in vitro , aminopterin is being investigated in clinical trials in leukemia as a potentially superior antifolate to methotrexate. (cloudfront.net)
  • [7] Similar congenital abnormalities have been documented with methotrexate, and collectively their teratogenic effects have become known as the fetal aminopterin syndrome . (cloudfront.net)
  • Methotrexate is a stable derivative of aminopterin, a folate antimetabolite. (phcog.com)
  • Gbs has well recognized human teratogens exposure type fetal effect drugs aminopterin methotrexate growth restriction, microcephaly, and mental health services administration, mesolimbic da system is the production of platelets could be due to very premature infants and children, have a pneumopericardium drained by needle aspiration frequently have aggressive malignancies. (umaine.edu)
  • Both the enzymically active form and the isomer having the opposite configuration at carbon 6 inhibited the influx of enzymically synthesized (+)-5-methyltetrahydrofolate, methotrexate, and aminopterin. (elsevier.com)
  • The most striking effect is observed with ternary complexes containing methotrexate or aminopterin and NADPH: maximal retention of the labeled protein in the immunoprecipitation assay is reduced to approximately 30% of its original value with dihydrofolate reductase alone due to a decrease in both the affinity and lifetime of the antibody-protein complex at one or more antigenic sites. (nih.gov)
  • ClonaCell™-HY AOF Expansion Medium is an animal origin-free (AOF) and serum-free liquid medium optimized for hybridoma expansion after hypoxanthine, aminopterin, thymidine (HAT) selection. (stemcell.com)
  • The medium contains hypoxanthine and thymidine (HT) and is used to wean hybridomas off aminopterin used during the selection process. (stemcell.com)
  • Only myeloma cells that do not secrete antibody are used, and these cells also lack the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) gene, making them sensitive to hypoxanthine-aminopterin-thymine (HAT) media that contains aminopterin that blocks DNA synthesis, and thus cell division. (labmanager.com)
  • If subculturing is carried out in a medium containing hypoxanthine, aminopterin, and thymidine (i.e. (biologydiscussion.com)
  • Myeloma cells are refined with 8 azaguanine to testing the susceptibility to the hypoxanthine aminopterin-thymidine (HAT) medium utilized after cell combination. (get2fiu.com)
  • The cells are then cultivated in the hypoxanthine aminopterin-thymidine (HAT) medium, only the hybridoma cells develop, the rest will gradually die. (get2fiu.com)
  • Pseudoaminopterin syndrome is a developmental anomalies syndrome that resembles the aminopterin embryopathy (see this term) without history of fetal exposure to aminopterin. (orpha.net)
  • This prescription is additionally used to recharge folic corrosive in the body and lessen the poisonous quality caused because of the organization of folic corrosive foes, for example, aminopterin, pyrimethamine, trimethoprim, triamterene, and so forth. (gmsanjivani.com)
  • Soon after the discovery of folic acid in 1941, its chemical analog and antifolate, aminopterin was developed and used in rheumatoid arthritis (RA) [ 1 ]. (biomedcentral.com)
  • Aminopterin (or 4-aminopteroic acid), the 4-amino derivative of folic acid , is an antineoplastic drug with immunosuppressive properties often used in chemotherapy . (cloudfront.net)
  • Dr. Farber eventually demonstrated that aminopterin, a compound related to the vitamin folic acid, produced remissions in children with acute lymphoblastic leukemia (ALL). (samjeffersfoundation.org)
  • Alcohol, methyl mercury, aminopterin, pyriproxifene, cocaine and heroin are known causes of the condition, causing the baby's skull bones to close before their time. (hickeysolution.com)
  • This of import fact led to the development of the first antifolate drug, aminopterin or 4-aminopteroyl-glutamic acid. (hstreasures.com)
  • Aminopterin syndrome. (medscape.com)
  • When a similar cluster of abnormalies appears in the absence of exposure to antifolates it is referred to as aminopterin-like syndrome without aminopterin. (cloudfront.net)
  • Drugs such as aminopterin and Cytoxan (cancer drugs), androgens and diethylstilbesterol (hormones), and coumarin (anticoagulant drug) must be avoided. (targetwoman.com)
  • A decade later, the first chemotherapy drug, 4-aminopteroic acid (aminopterin), was developed after understanding the action of folate in the body. (pasioonline.com)
  • Aminopterin is widely used in selection media (such as HAT medium ) for cell culture , particularly in the development of hybridomas , which secrete monoclonal antibodies . (cloudfront.net)
  • Merely another chemical modification in a series of attempts by the research team, the new drug, aminopterin, was not expected to do anything dramatic, but Farber and the team had come such a long way since the middle of 1947, when he'd actually done the opposite of what he was doing now. (medscape.com)
  • Our findings will give new directions to vaccines and therapies which will potentially invert these dysfunctional cells and invite them to regulate HIV-1 Aminopterin replication but also provide in "Surprise and Eliminate" HIV curative strategies. (harrisbee.org)
  • Aminopterin blocked a critical chemical reaction needed for DNA replication. (samjeffersfoundation.org)
  • Menu Foods first announced that aminopterin, a chemical used to poison rats, was found in canned foods. (opednews.com)
  • [10] Aminopterin has a single-dose LD Lo of 2.5 mg/kg when orally administered to rats. (cloudfront.net)
  • Tests from a New York State food laboratory pointed to a compound called aminopterin as the culprit in late March, but now the FDA is now focusing on something called melamine. (livescience.com)
  • On March 23, 2007, ABC News reported [12] that aminopterin was the chemical linked to the 2007 Menu Foods pet food contamination incident . (cloudfront.net)
  • Effect of pitressin tannate on the diabetes insipidus induced by aminopterin in the rat. (semanticscholar.org)
  • The aminopterin, maternal diabetes, hyperther- hospital serves as a referral centre for ob- mia, low socioeconomic status, and lack of stetric and gynaecologic problems and a folate have been shown to increase the risk prenatal intensive care unit for all other of NTD. (who.int)
  • During the period Aminopterin was marketed, the agent was used off-label to safely treat over 4,000 patients with psoriasis in the United States, producing dramatic clearing of lesions. (cloudfront.net)
  • These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T Aminopterin cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion. (harrisbee.org)
  • Launch During chronic viral attacks high antigenic tons constantly stimulate T cells resulting in progressive lack of function termed "T cell Aminopterin exhaustion" [1]. (harrisbee.org)
  • Anencephaly (pronounced an-en-SEF-uh-lee ) is a more severe, but less common, type of NTD. (nih.gov)