OBJECTIVES:. I. To determine the dose limiting toxicity (DLT) and maximally tolerated dose (MTD) of PTK/ZK and pemetrexed disodium when given in combination.. II. To describe the toxicities associated with the combination of PTK/ZK with pemetrexed disodium.. III. To evaluate the pharmacokinetic interaction of combination of PTK/ZK with pemetrexed disodium at the MTD (Group II).. IV. To evaluate the intracellular content of pemetrexed disodium polyglutamates as a measure of activity of pemetrexed disodium transport and activation enzymes in the MTD expansion cohort (Group II).. V. To evaluate polymorphisms and gene expression of pemetrexed disodium target genes, and genes encoding enzymes involved in the transport, activation, and inactivation of pemetrexed disodium, and correlate haplotype-tagged SNPs or gene expression levels with intracellular levels of pemetrexed disodium polyglutamates, toxicity and/or efficacy or pemetrexed disodium in Group II.. VI. To evaluate pharmacogenetic, metabolic ...
RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium and celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving gemcitabine hydrochloride or pemetrexed disodium together with carboplatin is more effective with or without celecoxib in treating non-small cell lung cancer.. PURPOSE: This randomized phase III trial is studying gemcitabine hydrochloride, pemetrexed disodium, and carboplatin to compare how well they work when given together with celecoxib or a placebo in treating patients with advanced non-small cell lung cancer. ...
Guanine is the most readily oxidized of the four DNA bases, and guanine oxidation products cause G:C-T:A and G:C-C:G transversions through DNA replication. 8-Oxo-7,8-dihydroguanine (8-oxoG) causes G:C-T:A transversions but not G:C-C:G transversions, and is more readily oxidized than guanine. This review covers four major findings. (i) 2,2,4-Triamino-5(2H)-oxazolone (Oz) is produced from guanine and 8-oxoG under various oxidative conditions. Guanine is incorporated opposite Oz by DNA polymerases, except REV1. (ii) Several enzymes exhibit incision activity towards Oz. (iii) Since the redox potential of GG is lower than that of G, contiguous GG sequences are more readily oxidized by a one-electron oxidant than a single guanine, and OzOz is produced from GG in double-stranded DNA. Unlike most DNA polymerases, DNA polymerase ζ efficiently extends the primer up to full-length across OzOz. (iv) In quadruplex DNA, 3′-guanine is mainly damaged by one-electron oxidation in quadruplex DNA, and this damage
So my dad has NSCLC type adenocarcinoma. He has had 5 rounds of chemo with Carboplatin and Alimta. I just read that "ALIMTA is a chemotherapy drug used to treat certain kinds of non-small cell lung cancer (NSCLC) called advanced nonsquamous NSCLC." This is from the Alimta website (alimta.com). Now I am confused as to why my dad is on Alimta if its for nonsquamous type. Anyone else with adenocarcinoma been on Alimta? My dad is going to begin maintenance therapy with avastin but I was wondering if I should ask the doctor if there is other types of chemo we should try before going to maintenance therapy? Any thoughts?. Thanks in advance! ...
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Data presented today at the 42nd American Society of Clinical Oncology (ASCO) annual meeting in Atlanta, Ga., affirms that ALIMTA® (pemetrexed), manufactured and marketed by Eli Lilly and Company, offers patients with advanced non-small cell lung cancer (NSCLC) similar overall survival as docetaxel (Taxotere®).. The survival data were part of a large (n=571), randomized Phase III study to evaluate the efficacy and safety profile of Alimta as second-line therapy in NSCLC. First reported in 2003(i), the study found that patients in the Alimta arm achieved 8.3 months of median survival, whereas those in the docetaxel arm obtained 7.9 months. This updated analysis of data tracked patients from the same study nearly two years beyond the conclusion of the original study and found similar results. The updated data showed that patients who received Alimta experienced 8.3 months of median survival compared to 8.0 months for those in the docetaxel arm. "The data mirror previously reported results and ...
This phase I pilot trial studies how well atezolizumab, pemetrexed disodium, cisplatin, and surgery with or without radiation therapy in treating patients
Current peaks related to guanine oxidation of the probe-modified-PGE after (a) and before hybridization with DENV-3 (b); in the presence of non-complementary se
Alimta infusion contains the active ingredient pemetrexed disodium, which is a type of chemotherapy medicine for cancer called a cytotoxic antimetabolite.
Learn how ALIMTA may help treat advanced nonsquamous non-small cell lung cancer. Find information about ALIMTA and platinum chemotherapy (carboplatin or cisplatin) in combination with KEYTRUDA® (pembrolizumab).
TY - JOUR. T1 - Toxicity of intracranial and intraperitoneal O6-benzyl guanine in combination with BCNU delivered locally in a mouse model. AU - Guarnieri, Michael. AU - Biser-Rohrbaugh, Ann. AU - Tyler, Betty Mae. AU - Gabikian, Patrik. AU - Bunton, Tracie E.. AU - Ze Wu, Qing. AU - Weingart, Jon David. AU - Solomon, Benjamin. PY - 2002. Y1 - 2002. N2 - Purpose: The DNA-repair protein, O6-alkylguanine-DNA alkyl transferase, may account for resistance of CNS tumors to DNA-alkylating drugs, such as bis-(2-chloroethyl)-1-nitrosourea (BCNU). The therapeutic effects of BCNU can be potentiated by inhibiting the repair protein with an alkylated guanine analog, O6-benzyl guanine (O6BG). To investigate potential toxicity of this inhibition, we examined the effects of O6BG in mice treated with intracranial (i.c.) BCNU given via a biodegradable polymer. Methods: Mice were treated with escalating doses of BCNU chronically delivered i.c., and with chronically delivered O6BG. The O6BG was delivered via a ...
Condition: Malignant Mesothelioma. Estimated Enrollment: 153. Gender: All. Min Age: 18 Years. Age Group: Adult, Older Adult. Current Status: Completed. Study Results: No Results Available. Outcome Measures: Complete macroscopic resection (part 1), Loco-regional relapse-free survival (part 2), Response to neoadjuvant therapy (part 1), Adverse drug reaction to neoadjuvant therapy (part 1). Interventions: Cisplatin, Pemetrexed. Phase: Study Type: Interventional. Study Design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: None (Open Label),Primary Purpose: Treatment. Primary Completion Date: March 26, 2014. Completion Date: January 23, 2018. Last Posted Date: May 15, 2019. Location: Universitaetsklinikum Freiburg, Freiburg, Germany. Website Link: https://ClinicalTrials.gov/show/NCT00334594. ...
In this study, patients will receive either pemetrexed plus irinotecan or 5-fluorouracil (5-FU), leucovorin, and irinotecan.The purposes of this
We have prepared four complexes of the type [Re(guanine)(2)(X)(CO)(3)] (guanine = 9-methylguanine or 7-methylguanine, X = H(2)O or Br) in order to understand the factors determining the orientation of coordinated purine ligands around the [Re(CO)(3)](+) core. The 9-methylguanine ligand (9-MeG) was chosen as the simplest N(9) derivatized guanine, and 7-methylguanine (7-MeG) was chosen because metal binding to N(9) does not impose steric hindrance. Two types of structures have been elucidated by X-ray crystallography, an HH (head-to-head) and HT (head-to-tail) conformer for each of the guanines. All complexes crystallize in monoclinic space groups: [Re(9-MeG)(2)(H(2)O)(CO)(3)]ClO(4) (2) in P2(1)/n with a = 12.3307(10) A, b = 16.2620(14) A, c = 13.7171(11) A, and beta = 105.525(9) degrees, V = 2650.2(4) A(3), with the two bases in HT orientation and its conformer [Re(9-MeG)(2)(H(2)O)(CO)(3)]Br (3) in P2(1)/n with a = 15.626(13) A, b = 9.5269(5) A, c = 15.4078(13) A, and beta = 76.951(1) degrees, V = 2234.5
This trial assessed the efficacy and tolerability of pemetrexed [Alimta, LY231514, NSC 698037] + cisplatin [NSC 119875] in patients with advanced, persistent,
Among these four types of SNPs, C ↔ T/A ↔ G, A ↔ C/G ↔ T, A ↔ T, and C ↔ G, the neighborhood patterns of nucleotide distributions were, however, quite different from each other (Figure 2). For example, at the −1 site, the trend of nucleotide dynamics was A , T , C , G for the combined C ↔ T/A ↔ G transitions (Figure 2, A and B), T , A , G , C for the combined A ↔ C/G ↔ T transversions (Figure 2, C and D), T , A , C , G for the A ↔ T transversions (Figure 2E), and A , T , G , C for the C ↔ G transversions (Figure 2F), respectively. However, at the +1 site, the trend was G , A , T , C for the combined C ↔ T/A ↔ G transitions (Figure 2, A and B), T , A , G , C for the combined A ↔ C/G ↔ T transversions (Figure 2, C and D), A , T , G , C for the A ↔ T transversions (Figure 2E), and T , A , C , G for the C ↔ G transversions (Figure 2F), respectively.. For the C ↔ T/A ↔ G transitions (Figure 2, A and B), nucleotide A had a high average frequency of 0.3548 ...
Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (,6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been ...
Pemetrexed is a cancer medication that interferes with the growth and spread of cancer cells in the body. Pemetrexed is used to treat non-small cell lung cancer after other cancer medications have been tried without successful treatment. Pemetrexed is also used with another medication called cisplatin to treat...
This trial will assess the efficacy and tolerability of gemcitabine and pemetrexed in combination followed by pemetrexed and concurrent upper abdominal
Hi All. Its been some time since my last post. Would like to provide some update and get some insight on proper next step.. My mother had finished 4 cycles of carbo + alimta with minimal side effects. Her PET scan afterwards shown improvement in the lung and bone mets, and also her CEI has dropped from over 4000 to around 600. Symptom-wise she had also improved greatly that her cough had stopped completely. The doctors at our government sector followed their standard procedure to stop the carbo and remain alimta as maintenance therapy This is where things go the other way round. Her coughing resumed before the second alimta maintenance treatment and CEI had rose to over 700. Situation did not improve after the 3rd alimta only dose and a PET scan was arranged and it turns out the main tumor and also the bone/adrenal gland mets had all worsen. Doctor suggested alimta is of no use any more and suggested to start keytruda at 2mg/KG/3weeks as a next step (without PDL1 testing).. We consulted our ...
The first direct comparison of treating nonsquamous lung cancer with either pemetrexed or docetaxel in addition to cisplatin has shown that the two combinations achieve similar progression-free survival.
The aim of this study is to explore the Clinical Value of Sequential Gefitinib With Pemetrexed/Platinum compare with Pemetrexed/Platinum for Advanced NS
A guanine radical cation (G+.) was site-selectively generated in double-stranded DNA and the hole transport from G+. to a GGG unit in G+.(TTG)NGG sites (N=1-4) was analyzed. The overall rate of the charge tra
1PYJ: Solution structure of an O6-[4-oxo-4-(3-pyridyl)butyl]guanine adduct in an 11 mer DNA duplex: evidence for formation of a base triplex.
The transcribed strand of S. cattleya can be inferred to have an average guanine content of 37.85%, since the message strand has a cytosine content of 37.85%. In B. burgdorferi, the transcribed-strand guanine has dropped to 12.17%. The difference between the two is 25.68%. On the message strand, adenine content goes from 13.59% for S. cattleya to 38.71% for B. burgdorferi, a difference of 25.12%. The implication is that if organisms evolve along the general path of the regression line in the above graph, all of the increase in message-strand adenine content can be accounted for by the loss in transcribed-strand guanine content. (The loss of guanine, in this example, was 25.68%, which is comparable to the increase of adenine, 25.12%, differing by only two parts per hundred.) Other organisms show a similar pattern of the change in transcribed-strand guanine equaling the change in message-strand adenine ...
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My memory is a bit sketchy, but is it something to do with the fact that adenine and thymine are held together by two hydrogen bonds, but cytosine and guanine are held together by three hydrogen bodns and is therefore more stable ...
Guan has just learnt the four nucleobases in DNA: Adenine, Thymine, Cytosine and Guanine. Wait, GUANine. Guan is incredibly intrigued by this based named GUANine. "Was it named after me?" he thought to himself. "Surely it must be, I am so smart." After countless hours of searching Google for the origins of Guanine, his search turned out futile. There was no results found for "Wu Guanquns brilliant discovery of new nucleobase Guanine." Devastated, he turns back to his lego DNA play set and starts constructing DNA sequences. "ATTGCCGATTGACT," Guan made, "hmm, gene for awkwardness." "GCTAGCTAGCGCGTAT," Guan made another gene sequence, "hmm, gene for being weird." Guan starts off with an empty DNA string. He can then choose any one of four operations to do ...
Oxidative damage yields isolated electrons and their corresponding holes that can migrate along DNA. In the 6 July Nature Lewis et al. determine rate constants of ~5x107 s-1 and 5x106 s-1, respectively, for forward and return hole transport from a single guanine base to a double guanine base across a single adenine (Nature 2000, 406:51-53). These rates mean that electrons do not linger long enough to participate in strand-cleavage reactions. But the electrons move too slowly to avoid charge recombination, so DNA cannot act as a useful molecular wire. ...
مقاله ISI انگلیسی شماره 10645 - ترجمه نشده - موضوع : اقتصاد سلامت - 7 صفحه - سال انتشار : 2012 - منبع : الزویر ساینس دایرکت
Get an answer for DNA MoleculeUnder normal circumctances, it is not possible for adenine to pair up with guanine or cytosine, or for any other mismatches to occur. Describe the two factors that prevent a mismatch from occcuring. and find homework help for other Science questions at eNotes
Prevents viral reverse transcription of single-stranded RNA into double-stranded DNA, by inhibiting HIV reverse transcriptase ...
Hello again I have been off Alimta maintenance for about 1 1/2 months now and recovered a little from pretty severe side effects . The chemo lasted me for about 6 months before progression . Better than nothing . A recent biopsy shows loss of t790M as my only resistance mechanism . Im still on Tagrisso The next treatment will likely be another chemo. I have had a terrible
गुवानिन के रूपों के अतिसूक्ष्म मात्रा, अम्मोनियम सायनाइड (NH4CN) के पॉलीमराइज़ेशन से बनते हैं। लेवी एत. एल. द्वारा किए गए दो प्रयोगों से ज्ञात हुआ कि 10 mol•L−1 NH4CN को 80 °C पर चौबीस घंटे तक गर्म करने पर 0.0007% मिलता है, जबकि 0.1 mol•L−1 NH4CN को -20 °C पर पच्चीस वर्षों तक प्रशितन में रखने पर 0.0035% उपज मिलती है। इन परिणामों से ज्ञात होता है, कि गुवानिन प्राचीन काल में पृथ्वी पर उत्पादित हो पाई होगी। In 1984, Yuasa reported a 0.00017% yield of guanine after ...
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Ето и един сладкиш, който моята съквартирантка - италианка приготвяше преди години и го наричаше торта. Нека всеки да го нарича както иска, но десертът е с изключително интересен вкус. Плодчетата арония носят свежест на тортата, а силният аромат на кафето е силно тонзииращ. Аронията придава лека екзотичност на сладкиша и го прави изключително полезен (няма да се спирам на полезните действия на аронията - по гръцка митология в подготвителен клас учителката ни отдели предостатъчно време на питието от арония, което пиели боговете на Олимп). ...
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 ...
Maintenance therapy is associated with improved survival in non-small cell lung cancer (NSCLC), but few studies have compared active agents in this setting. In a phase III trial (AVAPERL trial) reported in the Journal of Clinical Oncology by Fabrice Barlesi, MD, PhD, of Aix Marseille University-Assistance Publique Hôpitaux de Marseille, and colleagues, patients with advanced nonsquamous NSCLC who had disease control after first-line treatment with platinum-based chemotherapy plus bevacizumab (Avastin) had significantly prolonged progression-free survival with maintenance bevacizumab/pemetrexed (Alimta) compared with bevacizumab alone.1 Toxicity was increased with bevacizumab/pemetrexed, although no new safety signals were observed.. Study Details. In this open-label multicenter trial, 376 patients with advanced nonsquamous NSCLC received first-line bevacizumab 7.5 mg/kg, cisplatin 75 mg/m2, and pemetrexed 500 mg/m2 once every 3 weeks for four cycles. Of these, 269 (72%) achieved disease control ...
Lomeguatrib (CAS: 192441-08-0) is a modified guanine base, which can repress the activity of DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (MGMT) with an IC50 value of 6 nM.
Pemetrexed-based chemotherapy may be another option for patients progressing on the second generation ALK-TKI. The PFS with pemetrexed based therapy for ALK-rearranged NSCLC patients is significantly longer than in patients without ALK rearrangements or with either EGFR or KRAS mutant [36-38]. Besides, pemetrexed was shown to be superior to docetaxel in both ORR (29% vs. 7%, respectively) and PFS (4.2 months vs. 2.6 months, respectively) for ALK-rearrangement NSCLC patients progressing on platinum-based chemotherapy [5]. All of these implied that pemetrexed should be preferentially considered for the treatment of ALK-rearrangement lung adenocarcinoma. However, the overall prognosis of patients with ALK-rearrangement NSCLC was still not encouraged.. Bevacizumab shows encouraging efficacy as the first or second-line therapy for patients with non-squamous NSCLC in some studies [39]. The phase III BEYOND trial compared the efficacy of carboplatin/paclitaxel plus placebo and carboplatin/paclitaxel ...
The combination of pemetrexed and cisplatin shows good clinical activity against mesothelioma and lung cancer. In order to study the potential cellular basis for this, and provide leads as to how to optimize the combination, we studied the schedule-dependent cytotoxic effects of pemetrexed and cisplatin against four human cancer cell lines in vitro. Tumor cells were incubated with pemetrexed and cisplatin for 24 h at various schedules. The combination effects after 5 days were analyzed by the isobologram method. Both simultaneous exposure to pemetrexed and cisplatin for 24 h and sequential exposure to cisplatin for 24 h followed by pemetrexed for 24 h produced antagonistic effects in human lung cancer A549, breast cancer MCF7, and ovarian cancer PA1 cells and additive effects in colon cancer WiDr cells. Pemetrexed for 24 h followed by cisplatin for 24 h produced synergistic effects in MCF7 cells, additive/synergistic effects in A549 and PA1 cells, and additive effects in WiDr cells. Cell cycle ...
Guanine is among the five nucleobases that is found in DNA and RNA. The formula of guanine is C5H5N5O, and is a planar and bicyclic molecule. Guanine has two forms, keto and enol forms. The keto form is the major form. Guanine, like adenine, is a derivative of purine and binds to cytosine through 3 hydrogen bonds. The amino group in the cytosine is the hydrogen donor and the C2 carbonyl and the N3 amine are the hydrogen-bond acceptors. In Guanine, the group at C6 acts as the hydrogen accepter, and the group at N1 and the amino group at C2 act as the hydrogen donors. The related nucleoside containing guanine and ribose is called guanosine and guanine bound to deoxyribose sugar is called deoxyguanosine. Guanine is capable of being hydrolyzed by strong acids to form ammonia, carbon monoxide, carbon dioxide, and glycine. Guanine oxidizes more readily than adenine, another purine-derivative nitrogenous base in nucleic acids. Guanine has a high melting point of 350°C due to the intermolecular ...
The protein O 6-alkylguanine-DNA alkyltransferase(alkyltransferase) is involved in the repair of O 6-alkylguanine and O 4-alkylthymine in DNA and plays an important role in most organisms in attenuating the cytotoxic and mutagenic effects of certain classes of alkylating agents. A genomic clone encompassing the Drosophila melanogaster alkyltransferase gene ( DmAGT ) was identified on the basis of sequence homology with corresponding genes in Saccharomyces cerevisiae and man. The DmAGT gene is located at position 84A on the third chromosome. The nucleotide sequence of DmAGT cDNA revealed an open reading frame encoding 194 amino acids. The MNNG-hypersensitive phenotype of alkyltransferase-deficient bacteria was rescued by expression of the DmAGT cDNA. Furthermore, alkyltransferase activity was identified in crude extracts of Escherichia coli harbouring DmAGT cDNA and this activity was inhibited by preincubation of the extract with an oligonucleotide containing a single O6-methylguanine lesion. ...
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Yavin, Eylon and Boal, Amie K. and Stemp, Eric D. A. et al. (2005) Protein-DNA charge transport: Redox activation of a DNA repair protein by guanine radical. Proceedings of the National Academy of Sciences of the United States of America, 102 (10). pp. 3546-3551. ISSN 0027-8424. PMCID PMC553321. https://resolver.caltech.edu/CaltechAUTHORS:YAVpnas05 ...
Health,...Alimta Zactima extend survival but cure remains out of reach studies...SATURDAY May 30 (HealthDay News) -- Certain drugs offer incremental y...Thats the conclusion of studies presented Saturday at the annual meet...Lung cancer remains Americas leading cancer killer and significant...,Drug,Trials,Show,Modest,Gains,Against,Lung,Cancer,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news