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Sample records for alfa-2b pemetrexed disodium

  1. Pemetrexed disodium (Eli Lilly).

    PubMed

    Norman, P

    2001-11-01

    Pemetrexed, a thymidylate synthase (TS) and transferase inhibitor, is in phase III trials with Eli Lilly as a potential treatment for several common solid tumors, including non-small cell lung cancer (NSCLC) and mesothelioma [321789], [410731]. Studies on pemetrexed have concluded that not only is the compound a TS inhibitor but also a potent inhibitor of human dihydrofolate reductase (DHFR). The results suggest that pemetrexed acts upon multiple intracellular targets and that the antitumor effect may be derived from its simultaneous inhibition of multiple folate-requiring enzymes [203662]: this compound has been designated as a multitargeted antifolate (MTA) [386680]. The drug also causes concentration- and time-dependent apoptosis [284380]. Other studies in which the 4-oxo group of the pyrimidine ring portion of pemetrexed was replaced with a hydrogen atom, demonstrated that the resulting analogs were potent DHFR inhibitors with very little activity against the enzymes glycinamide ribonucleotide formyltransferase (GARFT) and TS [310674]. In phase II European studies in 64 patients with advanced breast cancer, encouraging responses were seen in anthracycline-failure (23%) and anthracycline-refractory (19%) patients. Responses were observed in 28% of patients who had been previously treated with a taxane [326097]. Data from a phase II trial of pemetrexed (500 mg/m2 once every 21 days as a 10 min i.v. infusion) as a salvage therapy in advanced breast cancer showed that supplementation of the treatment regime with folic acid (FA) and vitamin B12 reduced its already manageable and tolerable toxicities [408821], [409650]. At doses of 500 mg/m2, the drug was also safely administered to 35 patients with impaired renal function [409953]. Phase I and II trials have shown that the main side effects include neutropenia, thrombocytopenia, mucositis, nausea and vomiting [203666], [272241]. Princeton University holds the patent rights to this drug under EP-00432677. In June

  2. Peginterferon Alfa-2b Injection (Sylatron)

    MedlinePlus

    ... injection is in a class of medications called interferons. It works by stopping the growth of cancer ... allergic to peginterferon alfa-2b injection (PegIntron, Sylatron), interferon alfa-2b (Intron), any other medications, or any ...

  3. Peginterferon Alfa-2b (PEG-Intron)

    MedlinePlus

    ... inject into your stomach if you are very thin. Use a different spot for each injection. Do not inject peginterferon alfa-2b into an area where the skin is sore, red, bruised, scarred, irritated, or infected; has stretch marks ...

  4. Maintenance therapy with interferon alfa 2b in Hodgkin's disease.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; Talavera, A; Nambo, M J; García, E L

    1998-08-01

    We performed a randomized clinical trial to assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with advanced Hodgkin's disease in complete remission (CR) after conventional chemotherapy. One hundred and thirty-five patients (stage IIIB-IV B) were initially treated with EBVD (epirubicin, bleomycin, vinblastine, dacarbazine). IF CR was achieved they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU three times a week for one year or no further treatment (control group). Clinical and laboratory characteristics at diagnosis were quite similar in both groups. After a median follow-up of 74.3 months (range 49 to 108), 61 out of 68 patients (91%; 95% confidence interval (CI): 76% to 97%) remain in first complete remission in the IFN-treated group compared to 38 out of 67 (58%; 95% CI: 49% to 71%) in the control group (p<.01). Overall survival was also better in the IFN treated group: 62 patients (92%; 95% CI: 82% to 97%) are alive free of disease at 7-years compared to 40 patients (67%, 95%: 55% to 76%) in the control group (p<.01). Toxicity secondary to IFN administration was mild and no dose modification was necessary during treatment. All patients received the planned dose of IFN. This was not an intent-to treat analysis. IFN administration as maintenance therapy was appears to be the only cause of improvement in outcome in these patients. We feel that IFN should be considered as maintenance therapy in patients with advanced Hodgkin's disease because this treatment improves the final outcome without the excessive toxicities of more aggressive therapeutic approaches such as bone marrow transplantation during first CR. We hope that IFN will be considered in future randomized clinical trials in order to define it's role in the treatment of Hodgkin's disease. PMID:9711927

  5. Modeling viral and drug kinetics: hepatitis C virus treatment with pegylated interferon alfa-2b.

    PubMed

    Powers, Kimberly A; Dixit, Narendra M; Ribeiro, Ruy M; Golia, Preeti; Talal, Andrew H; Perelson, Alan S

    2003-01-01

    Administration of peginterferon alfa-2b plus ribavirin results in an early hepatitis C virus (HCV) RNA decay followed by an increase as the drug concentration declines between doses. Upon administration of the next dose 1 week later, the same pattern is observed. We have incorporated pharmacokinetic/pharmacodynamic analysis into a model of viral dynamics to describe the effect that changes in drug concentration and effectiveness can have on viral levels. To illustrate the relationship between pharmacokinetics and viral dynamics, we fit the model to data from four HCV/human immunodeficiency virus co-infected patients, and obtained good agreement with the measured serum HCV RNA levels. We were able to account for the observed increases in HCV RNA, and estimate virion and drug half-lives that are in agreement with previous reports. Models incorporating pharmacokinetics are needed to correctly interpret viral load changes and estimate drug effectiveness in treatment protocols using peginterferon alfa-2b. PMID:12934163

  6. Macroscale production of crystalline interferon alfa-2b in microgravity on STS-52

    NASA Astrophysics Data System (ADS)

    Nagabhushan, Tattanahalli L.; Reichert, Paul; Long, Marianna M.; DeLucas, Lawrence J.; Bugg, Charles E.

    1995-01-01

    Macroscale crystallization of zinc interferon alfa-2b was achieved on STS-52 in October 1992 in the Protein Crystallization Facility. Conditions for crystallization were established by adapting a microscale vapor diffusion method to a macroscale temperature induction method. A series of earth based pilot experiments established conditions to reproducibly crystallize zinc interferon alfa-2b in high yield and under cleanroom conditions. As a control for the STS-52 mission, a ground experiment was run simultaneously and in the same configuration as the flight experiment. Greater than 95% of the available protein crystallized in both the ground and flight experiments. Using a battery of physical, biochemical and biological characterization assays, demonstrated that sample processing, polysulfone bottle confinement and the conditions used for crystallization did not have a negative effect on protein integrity. Redissolved crystals from the flight and ground experiments showed full biological activity in a cytopathic effect inhibition assay as compared to an interferon control standard. Morphometric analysis comparing the overall length and width of the derived crystals showed a 2.4 fold increase in the length and width of the space grown crystals as compared to earth grown crystals. Space grown crystals have remained a stable free flowing suspension for over 2 years. Based on these results, further experiments are envisioned to investigate macroscale crystallization of biologically active macromolecules in microgravity.

  7. Durability of responses to interferon alfa-2b in advanced hairy cell leukemia.

    PubMed

    Ratain, M J; Golomb, H M; Bardawil, R G; Vardiman, J W; Westbrook, C A; Kaminer, L S; Lembersky, B C; Bitter, M A; Daly, K

    1987-03-01

    Previous studies have demonstrated that significant hematologic improvement occurs in the majority of patients with hairy cell leukemia (HCL) treated with partially purified or recombinant interferon (IFN). Fifty-three patients received IFN alfa-2b for at least 3 months in a dose of 2 X 10(6) U/m2 subcutaneously thrice weekly. Of the 49 patients evaluable for response (at least 6 months of IFN therapy), there were ten complete responses and 29 partial responses for a total response rate of 80%. The peripheral blood counts and bone marrow continued to improve over the course of a full year of therapy. IFN was well tolerated, with no patients discontinuing therapy because of toxicity. Transient myelosuppression occurred in most patients during the first 1 to 2 months of therapy, occasionally precipitating a transfusion requirement. After IFN treatment was discontinued, there was a marked decrease in normal marrow elements and a relative increase in marrow hairy cells. This was associated with a transient increase in normal elements in the peripheral blood. Only one of 24 patients followed after receiving IFN for a median of 8.5 months (range, 3 to 16 months) has required further therapy. We conclude that low-dose IFN alfa-2b is highly effective in advanced HCL; responding patients should be treated for at least 1 year. The decision to initiate a second course of IFN therapy should be based primarily on peripheral blood counts and the clinical status of the patient rather than on the bone marrow. PMID:3814819

  8. Maintenance therapy with interferon alfa 2b in patients with diffuse large cell lymphoma.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; García, E L; Talavera, A; Guzmán, R

    1992-11-01

    Forty-eight consecutive patients with diffuse large cell lymphoma (DLCL) in complete remission (CR) after conventional chemotherapy were enrolled in a prospective clinical trial. The maintenance therapy was a random either nothing or interferon alfa 2b (IFN) 5.0 MU three times a week for one year. The median duration of CR in the patients treated with IFN has not been reached. After five years 60% of patients remain in CR compared to the control group who had a median CR of 40 months (p < 0.001). Actuarial five-years survival in the IFN treated patients was 88% compared to 42% in the control group (p < 0.001). Maintenance therapy with IFN has been beneficial in patients with DLCL with improvement of duration of CR and survival without the excessive toxicity of most common third generation regimen chemotherapy. We felt that IFN could be explored in most controlled clinical trials in patients with DLCL in CR after conventional chemotherapy. PMID:1487412

  9. Maintenance Therapy with Interferon Alfa 2b Improves Outcome in Aggressive Malignant Lymphoma.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; Talavera, A; García, E L; Nambo, M J

    1998-01-01

    To assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with malignant lymphoma on complete response after conventional chemotherapy we start a randomized clinical trial. One hundred and seventy patients were randomized to received either IFN 5.0 MU three time at week by one year or no further treatment, as control group. At a median follow-up of 9.0 years (range 4.3 to 11 years) median freedom from relapse (FFR) has not been reached in patients who received IFN, it is statistically significant to patients in control group with a median FFR of 60 months (p <.001). Actuarial curves show that at 10-years, 58 patients (66%, 95% confidence interval (CI) 53% to 79%) remain in first remission, statistical different to control group 33 patients (40%, 95% Cl: 33% to 57%) (p <.001). Event free survival (EFS) shown that a 10-years 63 patients (71%, 95% CI: 59% to 81%) are alive free of disease in the IFN arm compared to only 38 patients (45%, 95% CI: 37% to 57%) in the control group (p <.001). Toxicity was mild, 81 patients received the planned doses of IFN on time and 6 patients had transitory delay secondary to hematological toxicity (grade 1 or 2) and completed the treatment on 13 months. No late side effects has been observed. After a long term follow-up we confirm that IFN used as maintenance therapy improves outcome in patients with aggressive malignant lymphoma who were in complete remission after conventional chemotherapy without excessive toxicity. We feld that IFN will be consider in controlled clinical trials to define the role of this therapeutic option. PMID:27414082

  10. Safety and Efficacy of Combination Immunotherapy With Interferon Alfa-2b and Tremelimumab in Patients With Stage IV Melanoma

    PubMed Central

    Tarhini, Ahmad A.; Cherian, John; Moschos, Stergios J.; Tawbi, Hussein A.; Shuai, Yongli; Gooding, William E.; Sander, Cindy; Kirkwood, John M.

    2012-01-01

    Purpose We tested the hypothesis that the combination of tremelimumab and interferon alfa-2b acting via different and possibly synergistic mechanisms would overcome tumor immune tolerance and lead to significant and durable clinical responses. Patients and Methods We conducted a phase II study in which patients were administered tremelimumab 15 mg/kg/course (three cycles [one cycle = 4 weeks]) intravenously every 12 weeks. High-dose interferon alfa-2b (HDI) was administered concurrently, including intravenous induction at 20 MU/m2/d for 5 d/wk for 4 weeks followed by maintenance at 10 MU/m2/d subcutaneously three times a week for 8 weeks per course. From course 2 onward, HDI maintenance was administered subcutaneously. Results Thirty-seven patients with American Joint Committee on Cancer stage IV (9M1a, 6M1b, and 22M1c) were enrolled. Two patients had previously treated brain metastases. Grades 3 and 4 toxicities included neutropenia (six patients; 17%), diarrhea/colitis (four patients; 11%), liver enzyme increase (four patients; 11%), rash (four patients; 11%), fatigue (15 patients; 40%), and anxiety/depression (five patients; 14%). Response data were available for 35 patients. The best objective response rate (RR; Response Evaluation Criteria in Solid Tumors) by intention to treat was 24% (90% CI, 13% to 36%; four complete responses [CRs] and five partial responses [PRs] that lasted 6, 6, > 12, > 14, > 18, 20, > 28, 30, and > 37 months, respectively). Fourteen patients (38%) had stable disease (SD) that lasted 1.5 to 21 months. The median progression-free survival was 6.4 months (95% CI, 3.3 to 12.1 months). The median overall survival (OS) was 21 months (95% CI, 9.5 to not reached). There was a weak association between therapy-induced autoimmunity and clinical benefits (CR/PR/SD; P = .0059), baseline C-reactive protein (CRP) less than or equal to 2.7× the upper limit of normal and clinical benefits (P = .0494) and improved probability of survival (P = .0032

  11. Treatment of Chronic Hepatitis due to Hepatitis C Virus (CH-C) in India: A Randomized Controlled Trial Comparing Daily Interferon-alfa-2b and Ribavirin with Daily Interferon-alfa-2b and Glycyrrhizin—A Multicenter Study

    PubMed Central

    Acharya, Subrat K; Sreenivas, V; Gupta, Siddharth Datta; Kumar, Shakti; Chawla, Yogesh K; Tandon, Anurag; Habeeb, Aejaz; Kar, Premashish; Chowdhury, Abhijit; Choudhuri, Gourdas; Sarin, Shiv K; Amarapurkar, DN; Arankalle, Vidya; Gupte, Mohan D; Gupta, Sushma; Mukherjee, Deepali; Seth, Divya; Goyal, Rohit; Tandon, Badri N

    2012-01-01

    Background and Aim Pegylated-interferon-alfa (PEG-IFN-α) with ribavirin is an established treatment in chronic hepatitis due to hepatitis C virus (HCV) (CH-C). Such treatment is expensive and in resource-poor countries such as India, alternative less expensive therapy is needed. Methods Multicenter randomized controlled trial comparing two treatment regimens (interferon-alfa-2b [IFN-α-2b] 3 million unit/day [MU/day] and ribavirin 1000 mg/day [I+R] vs IFN-α-2b 3 MU/day and glycyrrhizin 250 mg [I+G]) in CH-C. Viral, host characteristics and therapeutic responses were assessed (ICMR—6 months trial for chronic hepatitis—CTRI/2008/091/000105). Results One hundred and thirty-one patients meeting the inclusion criteria were randomized to I + G (n=64) or I+R (n=67) during the period February 2002 to May 2005. About 85% (I+G=53, I+R=58) completed 6 months of treatment and 89% of them (I+G=46, I+R=53) completed 6 months of follow-up after completion of treatment. Hepatitis C virus genotype 3 was the major type detected (71% patients). The mean log10 viral load (copies/mL), histological activity index, and fibrosis stage for all patients were 5.1 ± 0.98, 5 ± 2, and 2± 1.5, respectively. Sustained viral response (SVR) was significantly higher in I + R group than in I + G group (65.7% vs 46.9%, OR=2.2, P = 0.03). Treatment with I + G was associated with significantly lower frequencies of leukopenia (2% vs 17%, P <0.01) and anemia (8% vs 40%, P <0.001) as compared to treatment with I + R. Conclusion Genotype 3 HCV infection with low viral load is prevalent in India. Daily IFN with ribavirin showed significantly better responses. Leukopenia and anemia were significantly more in ribavirin group. Responses observed with IFN + ribavirin were similar to the reported response rates with PEG-IFN suggesting that this modality may be considered as a cheaper alternative of treatment for chronic hepatitis C. PMID:25755401

  12. A viral kinetic study using pegylated interferon alfa-2b and/or lamivudine in patients with chronic hepatitis B/HBeAg negative.

    PubMed

    Sypsa, Vassiliki-Anastasia; Mimidis, Konstantinos; Tassopoulos, Nicholas C; Chrysagis, Dimitrios; Vassiliadis, Themistoklis; Moulakakis, Antonios; Raptopoulou, Maria; Haida, Caterina; Hatzakis, Angelos

    2005-07-01

    We studied viral dynamic parameters in 44 chronic hepatitis B/hepatitis B e antigen (HBeAg)(-) patients treated with pegylated interferon alfa-2b (PEG-IFN) 100 or 200 microg weekly or lamivudine 100 mg daily or the combination of PEG-IFN 100 or 200 microg with lamivudine. Patients receiving PEG-IFN monotherapy exhibited viral load oscillations between weekly injections, which were resolved by the addition of lamivudine. The median pharmacological delay was estimated at 4.1, 5.8, and 1.8 hours in PEG-IFN monotherapy, PEG-IFN 100/200 microg + lamivudine, and lamivudine monotherapy, respectively (P = .44). The median half-life of free virus was 12.7 hours (range, 2.4-69.2 hours). The mean antiviral effectiveness of PEG-IFN 100/200 microg monotherapy was lower than that of lamivudine (82.6% vs. 96.4%; P = .005). The mean effectiveness of PEG-IFN 100 microg + lamivudine and PEG-IFN 200 microg + lamivudine was 92.8% and 94.4%, respectively. The half-life of infected cells ranged from 2.7 to 75 days. The median half-life of infected cells in patients receiving the combination regimens of PEG-IFN and lamivudine was similar to that of lamivudine patients (5.0 days vs. 6.0 days, P = .77). In conclusion, the addition of pegylated interferon alfa-2b in lamivudine treatment was found to neither enhance the potency of blocking HBV production nor the decay rates of infected cells. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). PMID:15962284

  13. Interferon Alfa-2b Injection

    MedlinePlus

    ... to acquired immunodeficiency syndrome (AIDS), to treat malignant melanoma (a cancer that begins in certain skin cells) ... a week for up to 6 months. malignant melanoma, inject the medication intravenously for 5 consecutive days ...

  14. Interferon Alfa-2b Injection

    MedlinePlus

    ... medication either subcutaneously or intramuscularly three times a week. HBV, inject the medication either subcutaneously or intramuscularly three times a week usually for 16 weeks. hairy cell leukemia, inject ...

  15. Fostamatinib Disodium

    PubMed Central

    McAdoo, Stephen P.; Tam, Frederick W. K.

    2012-01-01

    The non-receptor tyrosine kinase Syk has a diverse range of biological functions, including a critical role in the intracellular signalling cascade for the surface immunoglobulin receptor on B lymphocytes, and the Fc receptor expressed on numerous immune effector cells. It is therefore seen as a potential therapeutic target in a variety of conditions, including autoimmune, allergic and malignant diseases. Fostamatinib disodium is the orally bioavailable prodrug of R406, a relatively selective small molecule inhibitor of Syk, that has accordingly shown activity in numerous cell types in vitro, and efficacy in a remarkable range of animal models in vivo, including rodent models of asthma, inflammatory arthritis, lupus, glomerulonephritis, diabetes and lymphoma. Success in these models has translated to phase II clinical trials in autoimmune thrombocytopenia, lymphoma and, most notably, rheumatoid arthritis, in which larger phase III trials are currently in progress. Whilst the diverse biological functions of Syk, coupled to the potential off-target effects of this kinase inhibitor are a source of possible toxicity, the available data thus far augurs well for future clinical use of Fostamatinib in a wide range of human diseases. PMID:23284223

  16. Cost-effectiveness analysis of treatment with peginterferon-alfa-2a versus peginterferon-alfa-2b for patients with chronic hepatitis C under the public payer perspective in Brazil

    PubMed Central

    2013-01-01

    Background Chronic hepatitis C affects approximately 170 million people worldwide, and thus being one of the main causes of chronic liver disease. About 20% of patients with chronic hepatitis C will develop cirrhosis over 20 years, and present an increased risk of developing hepatic complications. Sustained virological response (SVR) is associated with a better prognosis compared to untreated patients and treatment failures. The objective of this analysis was to compare treatment costs and outcomes of pegylated interferon-alfa-2a versus pegylated interferon-alfa-2b, both associated with ribavirin, in the therapeutic scheme of 24 weeks and 48 week for hepatitis C genotypes 2/3 and genotype 1, respectively, under the Brazilian Public Health System (SUS) scenario. Methods To project disease progression, a Markov model was built based on clinical stages of chronic disease. A Delphi panel was conducted to evaluate medical resources related to each stage, followed by costing of related materials, services, procedures and pharmaceutical products. The evaluation was made from a public payer perspective. The source used for costing was government reimbursement procedures list (SAI/SIH–SUS). Drug acquisition costs were obtained from the Brazilian Official Gazette and “Banco de Preços em Saúde” (government official source). It was assumed a mean patient weight of 70 kg. Costs were reported in 2011 Brazilian Reais (US$1 ≈ $Brz1.80). A systematic review followed by a meta-analysis of the 7 identified randomized controlled trials (RCTs) which compared pegylated interferons, was conducted for obtaining relative efficacy of both drugs: for genotype 2/3, mean rate of SVR was 79.2% for peginterferon-alfa-2a and 73.8% for peginterferon-alfa-2b. For genotype 1, SVR mean rate was 42.09% versus 33.44% (peginterferon-alfa-2a and peginterferon-alfa-2b respectively). Time horizon considered was lifetime. Discount rate for costs and outcomes was 5%, according to Brazilian

  17. Efficacy and tolerability of peginterferon alfa-2a or alfa-2b plus ribavirin in the daily routine treatment of patients with chronic hepatitis C in Germany: the PRACTICE study.

    PubMed

    Witthoeft, T; Hueppe, D; John, C; Goelz, J; Heyne, R; Moeller, B; Teuber, G; Wollschlaeger, S; Baumgarten, A; Simon, K-G; Moog, G; Dikopoulos, N; Mauss, S

    2010-07-01

    In randomized clinical trials, treatment with peginterferon plus ribavirin (RBV) results in a sustained virological response (SVR) in around half of hepatitis C virus genotype 1-infected and 80% of genotype 2/3-infected individuals. This study aimed to evaluate efficacy and tolerability of peginterferon alfa-2a plus RBV compared with peginterferon alfa-2b plus RBV for the treatment of chronic hepatitis C in routine clinical practice. The intent-to-treat cohort consisted of 3414 patients treated with either peginterferon alfa-2a plus RBV (Group A) or peginterferon alfa-2b plus RBV (Group B) in 23 centres participating in the large, multicentre, observational PRACTICE study. Collected data included baseline characteristics, treatment regimen, RBV dose and outcome. Rates of early virological response, end of treatment response and SVR were 76.6%, 75.7% and 52.9% in Group A, and 70.2%, 65.6% and 50.5% in Group B, respectively. In patients matched by baseline parameters, 59.9% of patients in Group A and 55.9% in Group B achieved an SVR (P < or = 0.051). In genotype 1-infected patients matched by baseline parameters and cumulative RBV dose, SVR rates were 49.6% and 43.7% for Group A and Group B, respectively (P < or = 0.047); when matched by baseline parameters and RBV starting dose, SVR rates were 49.9% and 44.6%, respectively (P = 0.068). Overall, 21.8% of group A and 29.6% of group B patients discontinued treatment (P < or = 0.0001). The efficacy and tolerability of peginterferon plus RBV in this large cohort of patients treated in routine daily practice was similar to that in randomized clinical trials. In matched pairs analyses, more patients achieved an SVR with peginterferon alfa-2a compared with peginterferon alfa-2b. PMID:20158603

  18. Peginterferon Alfa-2b Injection (Sylatron)

    MedlinePlus

    ... 2b injection is used in people with malignant melanoma (a life-threatening cancer that begins in certain ... is used to reduce the chance that malignant melanoma will come back and must be started within ...

  19. Peginterferon Alfa-2b (PEG-Intron)

    MedlinePlus

    ... alcohol pad. Remove the protective needle cap and fill the syringe with air by pulling the plunger back to the 0.7 mL mark on the ... protective cap from the needle of the syringe. Fill the syringe with air by pulling the plunger back to the mL mark that matches your prescribed ...

  20. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.360 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace- tate... food additive contains a minimum of 99 percent disodium ethylenediaminetetraacetate...

  1. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.360 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace- tate... food additive contains a minimum of 99 percent disodium ethylenediaminetetraacetate...

  2. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.360 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace- tate... food additive contains a minimum of 99 percent disodium ethylenediaminetetraacetate...

  3. Pemetrexed (Alimta) in small cell lung cancer.

    PubMed

    Socinski, Mark A

    2005-04-01

    Small cell lung cancer (SCLC) comprises approximately 13% of all lung cancers. In limited stage (LS)-SCLC, combined-modality therapy represents the standard of care. Therapy should be approached curatively in fit patients with a good performance status because 5-year survival rates approach 26% in aggressively treated patients. In contrast, cure is not possible in extensive stage (ES)-SCLC with median 2-year survival rates with current therapy remaining at less than 10%. Pemetrexed (Alimta; Eli Lilly and Co, Indianapolis, IN) is a novel, multi-targeted antifolate that inhibits several folate-dependent enzymes involved in purine and pyrimidine synthesis, and is active as a single-agent or in combination with a platinum in both non-small cell lung cancer and malignant pleural mesothelioma. Pemetrexed/platinum combinations appear active in ES-SCLC based on objective response rates observed in a randomized phase II trial. However, no survival data is yet available from this trial. The toxicity profile of both cisplatin and carboplatin in combination with pemetrexed was extremely favorable, as was the ability to deliver full doses of each of the component drugs. Given the limited options available for patients in the relapsed setting, the activity of single-agent pemetrexed is interesting. Also, preliminary data indicates that full doses of carboplatin/pemetrexed can be administered with thoracic radiation therapy, supporting a future clinical trial initiative in LS-SCLC. PMID:15818532

  4. 21 CFR 582.6290 - Disodium phosphate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Disodium phosphate. 582.6290 Section 582.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Disodium phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is...

  5. 21 CFR 582.6290 - Disodium phosphate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Disodium phosphate. 582.6290 Section 582.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Disodium phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is...

  6. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Disodium EDTA. 172.135 Section 172.135 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Food Preservatives § 172.135 Disodium EDTA. The food additive disodium EDTA...

  7. 21 CFR 182.6290 - Disodium phosphate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Disodium phosphate. 182.6290 Section 182.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6290 Disodium phosphate. (a) Product. Disodium...

  8. 21 CFR 582.6290 - Disodium phosphate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Disodium phosphate. 582.6290 Section 582.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Disodium phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is...

  9. 21 CFR 582.6290 - Disodium phosphate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Disodium phosphate. 582.6290 Section 582.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Disodium phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is...

  10. 21 CFR 582.6290 - Disodium phosphate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Disodium phosphate. 582.6290 Section 582.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Disodium phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is...

  11. Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

    ClinicalTrials.gov

    2015-04-09

    Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Metastatic Cancer; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous Condition; Secondary Myelofibrosis; Unspecified Adult Solid Tumor, Protocol Specific

  12. 21 CFR 182.6290 - Disodium phosphate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Disodium phosphate. 182.6290 Section 182.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is generally recognized...

  13. 21 CFR 182.6290 - Disodium phosphate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Disodium phosphate. 182.6290 Section 182.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is generally recognized...

  14. 21 CFR 182.6290 - Disodium phosphate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Disodium phosphate. 182.6290 Section 182.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is generally recognized...

  15. 21 CFR 182.6290 - Disodium phosphate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Disodium phosphate. 182.6290 Section 182.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is generally recognized...

  16. Molecular Aggregation in Disodium Cromoglycate

    NASA Astrophysics Data System (ADS)

    Singh, Gautam; Agra-Kooijman, D.; Collings, P. J.; Kumar, Satyendra

    2012-02-01

    Details of molecular aggregation in the mesophases of the anti-asthmatic drug disodium cromoglycate (DSCG) have been studied using x-ray synchrotron scattering. The results show two reflections, one at wide angles corresponding to π-π stacking (3.32 å) of molecules, and the other at small angles which is perpendicular to the direction of molecular stacking and corresponds to the distance between the molecular aggregates. The latter varies from 35 - 41 å in the nematic (N) phase and 27 -- 32 å in the columnar (M) phase. The temperature evolution of the stack height, positional order correlations in the lateral direction, and orientation order parameter were determined in the N, M, and biphasic regions. The structure of the N and M phases and the nature of the molecular aggregation, together with their dependence on temperature and concentration, will be presented.

  17. Recombinant Interferon Alfa-2b in Treating Patients With Melanoma

    ClinicalTrials.gov

    2016-05-17

    Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  18. Critical appraisal of pemetrexed in the treatment of NSCLC and metastatic pulmonary nodules

    PubMed Central

    Li, Xin; Wei, Sen; Chen, Jun

    2014-01-01

    Pemetrexed, a new multitarget antifolate antineoplastic agent, has significantly improved the overall survival in nonsquamous non-small-cell lung cancer patients. Presently, pemetrexed is recommended for first line treatment in combination with platinum derivatives, for second line treatment as a single agent and, more recently, as maintenance treatment after first line chemotherapy. In this article we critically appraise the status of pemetrexed including pharmacodynamics, pharmacokinetics, toxicity, and the cost effectiveness of pemetrexed, as well as the predictive biomarkers for pemetrexed based chemotherapy. PMID:24944517

  19. Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial

    PubMed Central

    Bielack, Stefan S.; Smeland, Sigbjørn; Whelan, Jeremy S.; Marina, Neyssa; Jovic, Gordana; Hook, Jane M.; Krailo, Mark D.; Gebhardt, Mark; Pápai, Zsuzsanna; Meyer, James; Nadel, Helen; Randall, R. Lor; Deffenbaugh, Claudia; Nagarajan, Rajaram; Brennan, Bernadette; Letson, G. Douglas; Teot, Lisa A.; Goorin, Allen; Baumhoer, Daniel; Kager, Leo; Werner, Mathias; Lau, Ching C.; Sundby Hall, Kirsten; Gelderblom, Hans; Meyers, Paul; Gorlick, Richard; Windhager, Reinhard; Helmke, Knut; Eriksson, Mikael; Hoogerbrugge, Peter M.; Schomberg, Paula; Tunn, Per-Ulf; Kühne, Thomas; Jürgens, Heribert; van den Berg, Henk; Böhling, Tom; Picton, Susan; Renard, Marleen; Reichardt, Peter; Gerss, Joachim; Butterfass-Bahloul, Trude; Morris, Carol; Hogendoorn, Pancras C.W.; Seddon, Beatrice; Calaminus, Gabriele; Michelagnoli, Maria; Dhooge, Catharina; Sydes, Matthew R.; Bernstein, Mark

    2015-01-01

    Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Results Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. Conclusion At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped

  20. Enhanced biological phosphorus removal employing EDTA disodium

    SciTech Connect

    Bojinova, D.; Velkova, R.

    1996-12-31

    The biological phosphorus removal is a promising alternative to the conventional chemical technologies for processing of phosphate raw materials. The object of this study was the effect of EDTA disodium on the biotreatment of tunisian phosphorite with the strain of Aspergillus niger. The incubation was carried out in two nutritive mediums, with different phosphate content. The experimental results showed that the additives of EDTA disodium in the nutritive medium increased the rate of extraction of P{sub 2}O{sub 5} and shortened significantly the time for biological leaching. 5 refs., 3 figs., 2 tabs.

  1. Positive response of a primary malignant pericardial mesothelioma to pemetrexed plus cisplatin followed by pemetrexed maintenance chemotherapy: A case report

    PubMed Central

    CHUNG, SANG MI; CHOI, SEONG JI; KIM, MIN JUNG; CHOI, JUNG YOON; KIM, HONG JUN; LEE, SUK-YOUNG; KANG, EUN JOO

    2016-01-01

    Primary malignant pericardial mesothelioma (PMPM) is a rare tumor with poor prognosis. Surgery is the treatment of choice, but numerous cases are inoperable. For the treatment of inoperable or metastatic cases, systemic chemotherapy is required. However, a standard chemotherapeutic regimen for the treatment of pericardial mesothelioma has not yet been established. Chemotherapy involving pemetrexed and cisplatin has been actively used in the treatment of pleural or peritoneal mesothelioma, and may be considered for the treatment of PMPM. The present study reports the case of a patient with PMPM with lung metastasis who demonstrated a positive response to treatment with pemetrexed and cisplatin followed by pemetrexed maintenance chemotherapy, leading to prolonged progression-free survival for 21 months. PMID:27347127

  2. High plasma exposure to pemetrexed leads to severe hyponatremia in patients with advanced non small cell lung cancer receiving pemetrexed-platinum doublet chemotherapy

    PubMed Central

    Gota, Vikram; Kavathiya, Krunal; Doshi, Kartik; Gurjar, Murari; Damodaran, Solai E; Noronha, Vanita; Joshi, Amit; Prabhash, Kumar

    2014-01-01

    Background Pemetrexed-platinum doublet therapy is a standard treatment for stage IIIb/IV nonsquamous non small cell lung cancer (NSCLC). While the regimen is associated with several grade ≥3 toxicities, hyponatremia is not a commonly reported adverse effect. Here we report an unusually high incidence of grade ≥3 hyponatremia in Indian patients receiving pemetrexed-platinum doublet, and the pharmacological basis for this phenomenon. Methods Forty-six patients with advanced NSCLC were enrolled for a bioequivalence study of two pemetrexed formulations. All patients received the pemetrexed-platinum doublet for six cycles followed by single-agent pemetrexed maintenance until progression. Pharmacokinetic blood samples were collected at predefined time points during the first cycle and the concentration-time profile of pemetrexed was investigated by noncompartmental analysis. Hyponatremic episodes were investigated with serum electrolytes, serum osmolality, urinary sodium, and urine osmolality. Results Sixteen of 46 patients (35%) had at least one episode of grade ≥3 hyponatremia. Twenty-four episodes of grade ≥3 hyponatremia were observed in 200 cycles of doublet chemotherapy. Plasma exposure to pemetrexed was significantly higher in patients with high-grade hyponatremia than in those with low-grade or no hyponatremia (P=0.063 and P=0.001, respectively). Pemetrexed clearance in high-grade hyponatremia was quite low compared with normal and low-grade hyponatremia (P=0.001 and P=0.055, respectively). Median pemetrexed exposure in this cohort was much higher than that reported in the literature from Western studies. Conclusion Higher exposure to pemetrexed is associated with grade ≥3 hyponatremia. The pharmacogenetic basis for higher exposure to pemetrexed in Indian patients needs further investigation. PMID:24940080

  3. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Disodium EDTA. 573.360 Section 573.360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food...

  4. Pemetrexed and cyclophosphamide combination therapy for the treatment of non-small cell lung cancer

    PubMed Central

    Li, Dong; He, Song

    2015-01-01

    Lung cancer is the leading cause of cancer-related mortality. This study was undertaken to investigate the efficacy and safety of adding regulatory T cell inhibitor cyclophosphamide to pemetrexed therapy for the second-line treatment of NSCLC with wild-type epidermal growth factor receptor (EGFR). A total of 70 patients were screened between March 2011 and December 2013, out of which 62 patients were enrolled in the study. Patients were randomized to receive 500 mg/m2 pemetrexed in combination with 20 mg/kg cyclophosphamide in a 21 day cycle (n=30) or 500 mg/m2 pemetrexed (n=32), and followed up for 30 months. Disease progression was observed in 23 patients in the pemetrexed plus cyclophosphamide arm and 27 patients in the pemetrexed monotherapy arm. Median progression-free survival was 3.6 months (95% confidence interval [CI], 1.3 to 5.9 months) in the pemetrexed plus cyclophosphamide arm and 2.2 months (95% CI, 1.3 to 3.1 months) in the pemetrexed monotherapy arm. The 6-month PFS rates were 22% (95% CI, 10 to 34) and 14.5% (95% CI, 6 to 23) in the pemetrexed plus cyclophosphamide arm and pemetrexed monotherapy arm, respectively. Median overall survival was 9.8 months for the pemetrexed combination therapy arm and 8.8 months for the pemetrexed arm, and the 1-year survival rates were 46% and 33%, respectively. The present study showed that pemetrexed in combination with low-dose cyclophosphamide may be a better treatment approach than pemetrexed monotherapy when considering second-line treatment for wild-type EGFR NSCLC. PMID:26823793

  5. Prospective phase II study of cisplatin plus pemetrexed with maintenance of pemetrexed for advanced non-squamous cell non-small cell lung cancer in Japan

    PubMed Central

    Asami, Kazuhiro; Kawahara, Masaaki; Hirashima, Tomonori; Suzuki, Hidekazu; Okishio, Kyoichi; Omachi, Naoki; Tamiya, Motohiro; Tamiya, Akihiro; Hirooka, Aya; Nakao, Keiko; Tsuji, Taisuke; Atagi, Shinji

    2014-01-01

    Background A previous study showed a survival benefit with maintenance therapy with pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). However, it remains unclear whether continuation maintenance therapy with pemetrexed is beneficial in Japanese patients. Here, we present our phase II study that assessed the efficacy and safety of cisplatin plus pemetrexed as induction chemotherapy, followed by maintenance therapy with pemetrexed in advanced NSCLC patients in Japan. Methods Chemotherapy-naïve patients received 500 mg/m2 pemetrexed and 75 mg/m2 cisplatin on day one every three weeks for four cycles. In patients who responded to therapy or achieved stable disease, pemetrexed was continued until disease progression. The primary endpoint of this study was the progression-free survival rate at six months (PFS-6). Results Of the 35 patients initially enrolled in the study, 18 (51%) received maintenance chemotherapy with pemetrexed. The median PFS was 6.7 months, and the PFS-6 was 60% (95% confidence interval [CI], 42–76%). Median overall survival (OS) was 15.5 months (95% CI, 8.3–22.7 months). The median PFS and OS in patients who received maintenance chemotherapy with pemetrexed were 9.5 months and 25.3 months, respectively. The most frequently noted severe toxicity during induction chemotherapy was neutropenia, which occurred in seven patients. Two patients discontinued maintenance therapy owing to prolonged grade 2 edema in one patient and grade 3 neutropenia in another. Conclusion Continuation maintenance chemotherapy with pemetrexed is associated with a survival benefit in patients who have completed induction chemotherapy for non-squamous NSCLC. PMID:26767015

  6. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-11-01

    Abacavir sulfate/lamivudine, Adalimumab, AdCD40L, Adefovir, Adefovir dipivoxil, Ambrisentan, Amlodipine, Amlodipine besylate/olmesartan medoxomil, AN-2728, Apixaban, Aripiprazole, Armodafinil, Atazanavir sulfate, Atomoxetine hydrochloride, Atrasentan, Azacitidine, Bevacizumab, Blinatumomab, Bortezomib, Bosentan, Carfilzomib, Caspofungin acetate, Cediranib, Cetuximab, Choriogonadotropin alfa, Clevudine, Clindamycin phosphate/benzoyl peroxide, Clofarabine, Daidzeol, Darunavir, Dasatinib, Decitabine, Deferasirox, Deforolimus, Degarelix acetate, Denenicokin, Dexlansoprazole, Duloxetine hydrochloride, Elacytarabine, Enfuvirtide, Enoxaparin, Entecavir, Eribulin mesilate, Erlotinib hydrochloride, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Ezetimibe/simvastatin, Forodesine hydrochloride, Fosamprenavir calcium, Gefitinib, Gemtuzumab ozogamicin, Golimumab, Imatinib mesylate, Imetelstat, Insulin gl'argine, Insulin glulisine, Interferon alfa-2b XL, Ivabradine hydrochloride, Lacosamide, Lenalidomide, Lintuzumab, Liposomal adriamycin, Liposomal belotecan, Liposome-encapsulated fentanyl, Lopinavir/ritonavir, Lutropin alfa, LY-207320, Maraviroc, Mecasermin, MKC-253, MP-470, NGR-TNF, Nilotinib hydrochloride monohydrate, Ofatumumab, Olmesartan medoxomil, Omacetaxine mepesuccinate, PAN-811, Panobinostat, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pemetrexed disodium, Perospirone hydrochloride, PF-734200, Phentermine/topiramate, Pimecrolimus, Pitavastatin calcium, Plerixafor hydrochloride, Pregabalin, Raltegravir potassium, Ramelteon, Ranibizumab, Recombinant Bet V1, Recombinant human insulin, Regadenoson, rhITF, Romidepsin, Rosuvastatin calcium, Ruboxistaurin hydrochloride, Rufinamide, Sapropterin dihydrochloride Saracatinib, SB-73, SC-599, Seliciclib, Sirolimus-eluting stent, Sorafenib, Sunitinib malate, Tadalafil, Tanespimycin, Tapentadol hydrochloride, Tegaserod maleate, Telbivudine, Tenofovir

  7. Rapamycin downregulates thymidylate synthase and potentiates the activity of pemetrexed in non-small cell lung cancer

    PubMed Central

    Tsurutani, Junji; Shiga, Hideaki; Arwood, Matthew L.; Komiya, Takefumi; Gills, Joell J.; Memmott, Regan M.; Dennis, Phillip A.

    2014-01-01

    Non-small cell lung cancer (NSCLC) accounts for 80–85% of lung cancer cases, and almost half of newly diagnosed patients have metastatic disease. Pemetrexed is a widely used drug for NSCLC and inhibits several folate-dependent enzymes including thymidylate synthase (TS). Increased expression of TS confers resistance to pemetrexed in vitro and predicts poor response to pemetrexed. Rapamycin is an mTOR inhibitor and suppresses cap-dependent synthesis of specific mRNA species. Here, we show that the combination of rapamycin and pemetrexed synergistically inhibits proliferation of NSCLC cells. Although pemetrexed as a single agent induced TS, pretreatment with rapamycin suppressed pemetrexed-induced TS expression. In vivo, the combination of rapamycin and pemetrexed inhibited growth of NSCLC xenografts, which correlated with decreased mTOR activity and suppression of pemetrexed-induced TS expression. The ability of rapamycin to enhance the efficacy of pemetrexed and prevent TS expression has implications for the design of Phase I and/or Phase II NSCLC clinical trials with mTOR inhibitors in combination with pemetrexed. PMID:24658085

  8. Disodium cromoglycate inhibits production of immunoglobulin E.

    PubMed

    Seo, S B; Park, S J; Park, S T; Cho, C C; Park, B H; Lee, S J; Kim, H M; Kajiuchi, T; Shin, T Y

    2001-05-01

    Disodium cromoglycate (DSCG) has been shown to inhibit the release of mediators from mast cells. In the present study, the effect of DSCG on active anaphylactic reaction was studied in mice. DSCG dose-dependently inhibited the active systemic anaphylactic reaction and serum immunoglobulin (Ig)E production induced by immunization with ovalbumin, Bordetella pertussis toxin and aluminum hydroxide gel. DSCG strongly inhibited IL-4-dependent IgE production by lipopolysaccharide-stimulated murine whole spleen cells. In the case of U266 human IgE-bearing B cells, DSCG also showed an inhibitory effect on the IgE production. These results suggest that DSCG has an anti-anaphylactic activity by inhibition of IgE production from B cells. PMID:11417850

  9. Three emerging new drugs for NSCLC: pemetrexed, bortezomib, and cetuximab.

    PubMed

    Dubey, Sarita; Schiller, Joan H

    2005-04-01

    Despite advances made in cytotoxic chemotherapy, the prognosis for patients with non-small cell lung cancer (NSCLC) continues to be poor. New, more effective drugs must be identified and developed to improve the outcome of these patients. Three drugs with promising activity in NSCLC are pemetrexed (Alimta; Eli Lilly and Company, Indianapolis, IN, http://www.lilly.com), bortezomib (Velcade; Millennium Pharmaceuticals, Inc., Cambridge, MA, http://www.mlnm.com), and cetuximab (Erbitux; ImClone Systems, Inc., New York, NY, http://www.imclone.com). Pemetrexed inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase, enzymes necessary for purine and pyrimidine synthesis, thus causing cell-cycle arrest in the S phase. Bortezomib, a proteasome inhibitor, interferes with the cytosolic protein degradation machinery, namely the ubiquitin-proteasome complex, causing breakdown of cell-cycle regulators and cell-cycle arrest. Cetuximab is a chimeric mouse-human antibody that inhibits ligand-dependent activation of the epidermal growth factor receptor, resulting in receptor internalization and inhibition of downstream pathways that, in turn, causes cell growth and progression. All three drugs are approved for different tumor types, and studies defining their role in NSCLC are under way. PMID:15821248

  10. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2120 Disodium EDTA-copper. (a) Identity. The... amounts consistent with good manufacturing practices in the coloring of shampoos which are cosmetics....

  11. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2120 Disodium EDTA-copper. (a) Identity. The... amounts consistent with good manufacturing practices in the coloring of shampoos which are cosmetics....

  12. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2120 Disodium EDTA-copper. (a) Identity. The... amounts consistent with good manufacturing practices in the coloring of shampoos which are cosmetics....

  13. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2120 Disodium EDTA-copper. (a) Identity. The... amounts consistent with good manufacturing practices in the coloring of shampoos which are cosmetics....

  14. The emerging role of pemetrexed (Alimta) and gemcitabine in non-small cell lung cancer.

    PubMed

    Le Chevalier, Thierry

    2003-08-01

    In recent years, several new cytotoxic agents have been investigated for the management of non-small cell lung cancer (NSCLC), including the antimetabolic gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and the new multitargeted antifolate pemetrexed (Alimta, Eli Lilly and Company), which are both among the most active agents in advanced NSCLC. Gemcitabine has become one of the key drugs in the management of NSCLC, alone or in association with platin compounds. Promising results have also been reported with pemetrexed used as a single-agent or in combination with cisplatin or gemcitabine. These results indicate that pemetrexed may also play a vital role in the treatment of NSCLC, malignant mesothelioma, and other solid tumors. Ongoing (and planned) trials are investigating the use of single-agent pemetrexed, or combinations with cisplatin, gemcitabine, and other cytotoxic agents in various malignancies. PMID:12947960

  15. Prediction of renal transporter mediated drug-drug interactions for pemetrexed using physiologically based pharmacokinetic modeling.

    PubMed

    Posada, Maria M; Bacon, James A; Schneck, Karen B; Tirona, Rommel G; Kim, Richard B; Higgins, J William; Pak, Y Anne; Hall, Stephen D; Hillgren, Kathleen M

    2015-03-01

    Pemetrexed, an anionic anticancer drug with a narrow therapeutic index, is eliminated mainly by active renal tubular secretion. The in vitro to in vivo extrapolation approach used in this work was developed to predict possible drug-drug interactions (DDIs) that may occur after coadministration of pemetrexed and nonsteroidal anti-inflammatory drugs (NSAIDs), and it included in vitro assays, risk assessment models, and physiologically based pharmacokinetic (PBPK) models. The pemetrexed transport and its inhibition parameters by several NSAIDs were quantified using HEK-PEAK cells expressing organic anion transporter (OAT) 3 or OAT4. The NSAIDs were ranked according to their DDI index, calculated as the ratio of their maximum unbound concentration in plasma over the concentration inhibiting 50% (IC50) of active pemetrexed transport. A PBPK model for ibuprofen, the NSAID with the highest DDI index, was built incorporating active renal secretion in Simcyp Simulator. The bottom-up model for pemetrexed underpredicted the clearance by 2-fold. The model we built using a scaling factor of 5.3 for the maximal uptake rate (Vmax) of OAT3, which estimated using plasma concentration profiles from patients given a 10-minute infusion of 500 mg/m(2) of pemetrexed supplemented with folic acid and vitamin B12, recovered the clinical data adequately. The observed/predicted increases in Cmax and the area under the plasma-concentration time curve (AUC0-inf) of pemetrexed when ibuprofen was coadministered were 1.1 and 1.0, respectively. The coadministration of all other NSAIDs was predicted to have no significant impact on the AUC0-inf based on their DDI indexes. The PBPK model reasonably reproduced pemetrexed concentration time profiles in cancer patients and its interaction with ibuprofen. PMID:25504564

  16. Pemetrexed/cisplatin as first-line chemotherapy for advanced lung cancer with brain metastases

    PubMed Central

    He, Guangzhao; Xiao, Xiaoguang; Zou, Man; Zhang, Chengliang; Xia, Shu

    2016-01-01

    Abstract Background: Brain metastases (BMs) are a common and serious complication of non-small cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT), surgery, and molecular targeted therapy are usually used to treat NSCLC with BM. Chemotherapeutic options for BM are limited by tumor resistance, ineffective agents, and the blood–brain barrier. Pemetrexed/cisplatin is the preferred chemotherapy in nonsquamous NSCLC, but the efficacy of this treatment for nonsquamous NSCLC with BM is uncertain. Methods: We present a case of nonsquamous NSCLC with asymptomatic BM presenting with irritating cough and right shoulder back pain (unknown sensitizing epidermal growth factor receptor mutations or anaplastic lymphoma kinase). Results: He benefited from administration of first-line chemotherapy of pemetrexed/cisplatin. Partial remission was achieved in the primary lesion of the lungs and BM lesion. He was further given 3 cycles of pemetrexed monotherapy and WBRT. Complete remission was further achieved in BM lesion. Conclusion: The findings of clinical trials and theoretical studies about the current pemetrexed/cisplatin in the treatment of nonsquamous NSCLC with BM are also summarized to provide a reference for the application of pemetrexed/cisplatin in nonsquamous NSCLC with BM. Whether or not pemetrexed/cisplatin is definitely effective in nonsquamous NSCLC with BM must be proven by subsequent phase III clinical trials. PMID:27512852

  17. Phase II study of pemetrexed and carboplatin plus bevacizumab, followed by maintenance pemetrexed and bevacizumab in Japanese patients with non-squamous non-small cell lung cancer.

    PubMed

    Yokoi, Takashi; Torii, Yoshitaro; Katashiba, Yuichi; Sugimoto, Hiroyuki; Tanijiri, Tsutomu; Ogata, Makoto; Inagaki, Noriko; Kibata, Kayoko; Hayashi, Mina; Niki, Maiko; Shimizu, Toshiki; Miyara, Takayuki; Kurata, Takayasu; Nomura, Shosaku

    2014-12-01

    The present study evaluated the efficacy and safety of pemetrexed, carboplatin and bevacizumab, followed by maintenance pemetrexed and bevacizumab, in chemotherapy-naïve patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC). The patients were administered pemetrexed (500 mg/m(2)), carboplatin (area under the concentration-time curve, 6.0 mg/ml × min) and bevacizumab (15 mg/kg) intravenously every three weeks for up to six cycles. Patients who did not experience tumor progression remained on maintenance pemetrexed and bevacizumab until disease progression or unacceptable toxicity occurred. The primary endpoint was the overall response rate. Of the 26 patients enrolled between March 2010 and April 2011, three were excluded due to brain metastases, therefore the intention-to-treat (ITT) population consisted of 23 patients. The median age was 64 years (range, 40-74 years) and 15 patients were male. In total, six patients had a performance status of 0, and 20 had stage IV tumors. The response rate was 69.6% [95% confidence interval (CI), 47.1-86.8], the disease control rate was 100% and the time to response was 1.2 months (95% CI, 0.72-1.93). The median progression-free survival time was 8.6 months (95% CI, 5.9-10.9) and the median overall survival time was 18.6 months (95% CI, 12.9-24.8). There were no grade 3 or worse hemorrhagic events and the feasibility was modest. Overall, pemetrexed and carboplatin plus bevacizumab, followed by maintenance pemetrexed and bevacizumab, was effective and tolerable in the patients with non-squamous NSCLC, and the time to response was relatively short. PMID:25364406

  18. Phase II study of pemetrexed and carboplatin plus bevacizumab, followed by maintenance pemetrexed and bevacizumab in Japanese patients with non-squamous non-small cell lung cancer

    PubMed Central

    YOKOI, TAKASHI; TORII, YOSHITARO; KATASHIBA, YUICHI; SUGIMOTO, HIROYUKI; TANIJIRI, TSUTOMU; OGATA, MAKOTO; INAGAKI, NORIKO; KIBATA, KAYOKO; HAYASHI, MINA; NIKI, MAIKO; SHIMIZU, TOSHIKI; MIYARA, TAKAYUKI; KURATA, TAKAYASU; NOMURA, SHOSAKU

    2014-01-01

    The present study evaluated the efficacy and safety of pemetrexed, carboplatin and bevacizumab, followed by maintenance pemetrexed and bevacizumab, in chemotherapy-naïve patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC). The patients were administered pemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve, 6.0 mg/ml × min) and bevacizumab (15 mg/kg) intravenously every three weeks for up to six cycles. Patients who did not experience tumor progression remained on maintenance pemetrexed and bevacizumab until disease progression or unacceptable toxicity occurred. The primary endpoint was the overall response rate. Of the 26 patients enrolled between March 2010 and April 2011, three were excluded due to brain metastases, therefore the intention-to-treat (ITT) population consisted of 23 patients. The median age was 64 years (range, 40–74 years) and 15 patients were male. In total, six patients had a performance status of 0, and 20 had stage IV tumors. The response rate was 69.6% [95% confidence interval (CI), 47.1–86.8], the disease control rate was 100% and the time to response was 1.2 months (95% CI, 0.72–1.93). The median progression-free survival time was 8.6 months (95% CI, 5.9–10.9) and the median overall survival time was 18.6 months (95% CI, 12.9–24.8). There were no grade 3 or worse hemorrhagic events and the feasibility was modest. Overall, pemetrexed and carboplatin plus bevacizumab, followed by maintenance pemetrexed and bevacizumab, was effective and tolerable in the patients with non-squamous NSCLC, and the time to response was relatively short. PMID:25364406

  19. Reaction of disodium cromoglycate with hydrated electrons

    SciTech Connect

    Carmichael, A.J.; Arroyo, C.M.; Cockerham, L.G.

    1988-01-01

    A possible mechanism by which disodium cromoglycate (DSCG) prevents a decrease in regional cerebral blood flow but not hypotension in primates following whole body gamma-irradiation was studied. Several studies have implicated superoxide radicals (O/sub 2//sup -/.) in intestinal and cerebral vascular disorders following ischemia and ionizing radiation, respectively. O/sub 2//sup -/. is formed during radiolysis in the reaction between hydrated electrons (e-aq) and dissolved oxygen. For this reason, the efficiency of DSCG to scavenge e-q and possibly prevent the formation of O/sub 2//sup -/. was studied. Hydrated electrons were produced by photolysis of potassium ferrocyanide solutions. The rate constant, k = 2.92 x 10(10) M-1s-1 for the reaction between e-aq and DSCG was determined in competition experiments using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). This spin trap reacts rapidly with e-aq followed by protonation to yield the ESR observable DMPO-H spin adduct. The results show that DSCG is an efficient e-aq scavenger and may effectively compete with oxygen for e-aq preventing the radiolytic formation of O/sub 2//sup -/..

  20. Pemetrexed clinical studies in performance status 2 patients with non-small cell lung cancer (Review)

    PubMed Central

    ZINNER, RALPH; GRUL, CARLA VISSEREN; SPIGEL, DAVID R.; OBASAJU, COLEMAN

    2016-01-01

    Because poor performance status (PS) is an independent prognostic factor in non-small cell lung cancer (NSCLC), PS scores are widely used by oncologists to make treatment decisions. Advanced NSCLC patients with an Eastern Cooperative Oncology Group PS of 2 have poor prognoses and are frequently excluded from clinical trials. This article reviews the efficacy and safety of pemetrexed in this patient group. We identified English-language literature (through March 2015) involving completed and ongoing studies through searches of PubMed, meeting abstracts, ClinicalTrials.gov and the European Clinical Trials Register; search terms included ‘pemetrexed,’ ‘NSCLC’ and ‘PS2’. Only studies reporting ≥1 subset analysis of PS2 patients receiving pemetrexed were chosen. Our search identified a total of ten pemetrexed studies in PS2 patients. Eight studies included only chemonaive patients, one study included both chemonaive patients and patients with one prior chemotherapy regimen and one study included only patients with one prior regimen. In subset analyses in these studies, PS2 patients had worse outcomes than PS0-1 patients regardless of treatment. In a phase 3 study, chemonaive advanced NSCLC patients with PS2 receiving pemetrexed-carboplatin versus pemetrexed experienced improved overall survival [hazard ratio (HR)=0.62; P=0.001], progression-free survival (HR=0.46; P<0.001) and response (P=0.032). This review confirms the poorer outcomes in PS2 vs. PS0-1 patients. Although it is not an approved combination therapy, in clinical studies, PS2 patients treated with pemetrexed plus carboplatin as first-line therapy had improved response rates and survival. Additional research on PS2 patients is needed. PMID:26530033

  1. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  2. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  3. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  4. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  5. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  6. Pemetrexed alters folate phenotype and inflammatory profile in EA.hy 926 cells grown under low-folate conditions

    PubMed Central

    Hammons, Andrea L.; Summers, Carolyn M.; Jochems, Jeanine; Arora, Jasbir S.; Zhang, Suhong; Blair, Ian A.; Whitehead, Alexander S.

    2014-01-01

    Elevated homocysteine is a risk marker for several major human pathologies. Emerging evidence suggests that perturbations of folate/homocysteine metabolism can directly modify production of inflammatory mediators. Pemetrexed acts by inhibiting thymidylate synthetase (TYMS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). EA.hy 926 cells grown under low (“Lo”) and high (“Hi”) folate conditions were treated with pemetrexed. The concentrations of several intracellular folate derivatives were measured using LC-MRM/MS. Lo cells had lower total folate concentrations and a different distribution of the intracellular folate derivatives than Hi cells. Treatment with pemetrexed caused a decrease in individual folate analytes. Microarray analysis showed that several genes were significantly up or down-regulated in pemetrexed treated Lo cells. Several of the significantly up-regulated transcripts were inflammatory. Changes in transcript levels of selected targets, including C3, IL-8, and DHFR, were confirmed by quantitative RT-PCR. C3 and IL-8 transcript levels were increased in pemetrexed-treated Lo cells relative to Lo controls; DHFR transcript levels were decreased. In Lo cells, IL-8 and C3 protein concentrations were increased following pemetrexed treatment. Pemetrexed drug treatment was shown in this study to have effects that lead to an increase in pro-inflammatory mediators in Lo cells. No such changes were observed in Hi cells, suggesting that pemetrexed could not modify the inflammatory profile in the context of cellular folate sufficiency. PMID:22975265

  7. Radiation recall dermatitis with soft tissue necrosis following pemetrexed therapy: a case report

    PubMed Central

    2009-01-01

    Introduction Radiation recall dermatitis is a well known but still poorly understood inflammatory reaction. It can develop in previously irradiated areas and has been shown to be triggered by a variety of different drugs, including cytostatic agents. Pemetrexed may cause radiation recall dermatitis in pre-irradiated patients. Case presentation We present the case of a 49-year-old Caucasian woman with non-small cell lung cancer who was initially treated with carboplatin and paclitaxel concomitant with radiotherapy after suffering a painful plexus brachialis infiltration. Due to disease progression, a second-line treatment with pemetrexed was started. A severe soft tissue necrosis developed despite steroid treatment and plastic surgery. Conclusion To the best of our knowledge, we present the first case of a patient with severe soft tissue necrosis in a pre-irradiated area after pemetrexed therapy. We believe that physicians treating patients with pemetrexed should be aware of the severe, possibly life-threatening effects that may be induced by pemetrexed after previous radiation therapy. PMID:19946510

  8. Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience

    PubMed Central

    2012-01-01

    Background Although first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment. Methods We retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease) lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment. Results Overall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively. Conclusions In our opinion, when a patient has a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression. PMID:22943698

  9. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-04-01

    Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, AMA1-C1/alhydrogel, Amlodipine besylate/atorvastatin calcium, Aripiprazole, Artesunate/amodiaquine, Asenapine maleate; Bosentan, Brivaracetam; Carisbamate, Clevudine, Clofarabine, Corticorelin acetate; Dasatinib; Elinogrel potassium, Entecavir, Erlotinib hydrochloride, Eslicarbazepine acetate, Etazolate; Fampridine, Fluarix, Fondaparinux sodium, Fulvestrant; Gabapentin enacarbil, GDC-0941, GI-5005, Golimumab; Imatinib mesylate, Lacosamide, Lapatinib ditosylate, Levetiracetam, Liraglutide, LOLA; Mecasermin, Morphine hydrochloride; Natalizumab, Nilotinib hydrochloride monohydrate; Olmesartan medoxomil, Omacetaxine mepesuccinate; Paclitaxel-eluting stent, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Poly I:CLC, Pralatrexate, Pregabalin; Ranolazine, Rasagiline mesilate, Retigabine hydrochloride, Rhenium Re-186 etidronate, Rosuvastatin calcium, Rotigotine, RTL-1000, Rufinamide; Sirolimus-eluting coronary stent, Sirolimus-eluting stent, Sorafenib, Stiripentol; Tiotropium bromide; Valsartan/amlodipine besylate, Varenicline tartrate; XL-184; Zoledronic acid monohydrate. PMID:20448862

  10. A new quantification method for assessing plasma concentrations of pemetrexed and its polyglutamate metabolites.

    PubMed

    Stoop, Marcel P; Visser, Sabine; van Dijk, Evert; Aerts, Joachim G J V; Stricker, Bruno H; Luider, Theo M

    2016-09-01

    Currently no quantification method exists for potentially therapeutically relevant polyglutamate metabolites of the drug pemetrexed which is used for the treatment of lung carcinoma patients. We developed and tested an LC-MS/MS-based analytical assay that uses isotope-labeled internal standards to quantify pemetrexed and its (poly)glutamate metabolites in clinical human plasma samples of lung carcinoma patients. UHPLC chromatography and triple quadrupole mass spectrometry showed an LLOQ of 0.2nmol/L for pemetrexed and an LLOQ of 0.5nmol/L for the two metabolites (one glutamate and two glutamate moieties covalently bound to the pemetrexed molecule, for which no other quantification methods have previously been published). The recoveries for PMTX and its metabolites ranged between 30% and 67%. Precision and accuracy at a concentration of 20nmol/L for all four analytes was well below 15% CV. The precision (RSD) in the biological replicates of the separate days (within-run precision) as well as the reproducibility over several days (between-run precision), tested in the range of 5-250nmol/L, were all below 15%. Autosampler, benchtop and freeze-thaw cycle stability of the analytes was also demonstrated. To illustrate the new assay in a relevant biological context, concentrations of pemetrexed and the two metabolites were quantified in plasma samples of lung carcinoma patients treated with pemetrexed. The assay is straightforward, relatively easy to perform, and has potential for use in therapeutic drug monitoring in non-small cell lung carcinoma patients. PMID:27209449

  11. Prognostic value of serum leptin in advanced lung adenocarcinoma patients with cisplatin/pemetrexed chemotherapy

    PubMed Central

    MOU, WENJUN; XUE, HUI; TONG, HONGLI; SUN, SHENGJIE; ZHANG, ZHUHONG; ZHANG, CHUNYAN; SUN, QIYU; DONG, JING; WEN, XINYU; YAN, GUANGTAO; TIAN, YAPING

    2014-01-01

    Cisplatin/pemetrexed chemotherapy has been established as a standard treatment in lung adenocarcinoma. However, the response to the cisplatin/pemetrexed combination varies considerably among patients due to individual variations. Thus, novel biomarkers are required to aid the prediction of the response to the cisplatin/pemetrexed combination. We hypothesized that leptin expression may be a determinant for prognosis in lung adenocarcinoma patients with cisplatin/pemetrexed chemotherapy. Serum from consenting patients with lung adenocarcinoma were obtained for the measurement of leptin and associated tumor biomarkers. Leptin expression was measured by radioimmunoassay. Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA15-3, CA125, CA72-4, cytokeratin 19 fragment (CYFRA21-1) and neuron-specific enolase (NSE) expression were determined by electrochemiluminescence immunoassays. Serum squamous cell carcinoma antigen levels were measured using a microparticle enzyme immunoassay. The associations between serum leptin and tumor biomarker expression were evaluated by Spearman’s correlation analysis. Serum CEA, CA19-9, CA15-3, CA125, CA72-4, CYFRA21-1 and NSE levels showed no obvious difference among patients. However, a trend towards an improved prognosis was observed in patients with lower serum leptin at diagnosis and an increase during cisplatin/pemetrexed chemotherapy. The results indicated that the serum leptin level has prognostic indications in patients with advanced lung adenocarcinoma during cisplatin/pemetrexed chemotherapy, which indicates that it may be a useful marker for the prognosis of cancer patients undergoing chemotherapy treatment. PMID:24932291

  12. Prognostic value of serum leptin in advanced lung adenocarcinoma patients with cisplatin/pemetrexed chemotherapy.

    PubMed

    Mou, Wenjun; Xue, Hui; Tong, Hongli; Sun, Shengjie; Zhang, Zhuhong; Zhang, Chunyan; Sun, Qiyu; Dong, Jing; Wen, Xinyu; Yan, Guangtao; Tian, Yaping

    2014-06-01

    Cisplatin/pemetrexed chemotherapy has been established as a standard treatment in lung adenocarcinoma. However, the response to the cisplatin/pemetrexed combination varies considerably among patients due to individual variations. Thus, novel biomarkers are required to aid the prediction of the response to the cisplatin/pemetrexed combination. We hypothesized that leptin expression may be a determinant for prognosis in lung adenocarcinoma patients with cisplatin/pemetrexed chemotherapy. Serum from consenting patients with lung adenocarcinoma were obtained for the measurement of leptin and associated tumor biomarkers. Leptin expression was measured by radioimmunoassay. Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA15-3, CA125, CA72-4, cytokeratin 19 fragment (CYFRA21-1) and neuron-specific enolase (NSE) expression were determined by electrochemiluminescence immunoassays. Serum squamous cell carcinoma antigen levels were measured using a microparticle enzyme immunoassay. The associations between serum leptin and tumor biomarker expression were evaluated by Spearman's correlation analysis. Serum CEA, CA19-9, CA15-3, CA125, CA72-4, CYFRA21-1 and NSE levels showed no obvious difference among patients. However, a trend towards an improved prognosis was observed in patients with lower serum leptin at diagnosis and an increase during cisplatin/pemetrexed chemotherapy. The results indicated that the serum leptin level has prognostic indications in patients with advanced lung adenocarcinoma during cisplatin/pemetrexed chemotherapy, which indicates that it may be a useful marker for the prognosis of cancer patients undergoing chemotherapy treatment. PMID:24932291

  13. Pemetrexed for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer.

    PubMed

    Greenhalgh, J; McLeod, C; Bagust, A; Boland, A; Fleeman, N; Dundar, Y; Oyee, J; Dickson, R; Davis, H; Green, J; McKenna, E; Pearson, M

    2010-10-01

    This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of pemetrexed for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in accordance with the licensed indication, based upon the evidence submission from the manufacturer (Eli Lilly) to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The primary clinical outcome measure was progression free survival (PFS). Secondary outcomes included overall survival (OS), time to worsening of symptoms, objective tumour response rate, adverse events and changes in lung cancer symptom scale. Data for two populations were presented: patients with non-squamous NSCLC histology and patients with adenocarcinoma histology. The clinical evidence was derived from a double-blind, placebo-controlled randomised controlled trial (RCT), the JMEN trial. The trial compared the use of pemetrexed + best supportive care (BSC ) as maintenance therapy, with placebo + BSC in patients with NSCLC (n = 663) who had received four cycles of platinum-based chemotherapy (CTX) and whose disease had not progressed. In the licensed population (patients with non-squamous histology), the trial demonstrated greater median PFS for patients treated with pemetrexed than for patients in the placebo arm [4.5 vs 2.6 months; hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.36 to 0.55, p < 0.00001]. Median OS was also greater for the pemetrexed- treated patients (15.5 vs 10.3 months; HR 0.70; 95% CI 0.56 to 0.88, p = 0.002). In addition, tumour response and disease control rates were statistically significantly greater for patients who received pemetrexed. Patient survival rates at 1 year and 2 years were higher in the pemetrexed arm. The incremental cost-effectiveness ratios (ICERs) estimated by the manufacturer's model were 33,732 pounds per quality adjusted life-year (QALY

  14. Approval summary: pemetrexed maintenance therapy of advanced/metastatic nonsquamous, non-small cell lung cancer (NSCLC).

    PubMed

    Cohen, Martin H; Cortazar, Patricia; Justice, Robert; Pazdur, Richard

    2010-01-01

    On July 2, 2009, the U.S. Food and Drug Administration approved pemetrexed injection (Alimta® Injection; Eli Lilly and Company, Indianapolis, IN) for maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based doublet induction chemotherapy. A double-blind study of pemetrexed plus best supportive care versus placebo plus best supportive care was conducted. Pemetrexed, 500 mg/m(2) i.v., was administered every 21 days until disease progression. Folic acid, vitamin B(12), and a corticosteroid were given to all study patients. There were 663 randomized patients (pemetrexed, 441; placebo, 222). Treatments were well balanced with respect to baseline disease characteristics and stratification factors. The median overall survival (OS) time for intent-to-treat (ITT) patients was 13.4 months for patients receiving pemetrexed and 10.6 months for those receiving placebo (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.65-0.95; p = .012). Median OS times were 15.5 months versus 10.3 months for patients with nonsquamous histologies receiving pemetrexed and placebo, respectively (HR, 0.70; 95% CI, 0.56-0.88). The median OS time in patients with squamous histology receiving pemetrexed was 9.9 months, versus 10.8 months for those receiving placebo (HR, 1.07; 95% CI, 0.77-1.50). A significantly longer progression-free survival interval for both the ITT and nonsquamous patient populations receiving pemetrexed maintenance therapy was also observed. The most common (>5%) adverse reactions in patients receiving pemetrexed were hematologic toxicity, an increase in hepatic enzymes, fatigue, gastrointestinal toxicity, sensory neuropathy, and skin rash. PMID:21148615

  15. Feasibility Of Administering Adjuvant Chemotherapy Of Pemetrexed Followed By Pemetrexed/oxaliplatin Immediately Post-VATS In Patients With Completely Resected NSCLC

    PubMed Central

    He, Jianxing; Shao, Wenlong; Li, Shuben; Chen, Manyin; Chen, Hanzhang; Liu, Jun; Wang, Wei; Qiu, Yuan; Wang, Daoyuan

    2009-01-01

    Non-small cell lung cancer (NSCLC) accounts for the largest number of cancer deaths annually, worldwide. It seems reasonable to test a less toxic regimen also in early stages after complete (R0) resection of the tumor, where reduced toxicities might improve the feasibility of drug delivery, compliance and the convenience of treatment for the patient and hence perhaps improve survival. The main purpose of this phase II trial is to evaluate the clinical feasibility-in terms of patients without dose limiting toxicities or premature treatment withdrawal or death-of administering adjuvant chemotherapy of pemetrexed followed by pemetrexed/oxaliplatin immediately post-VATS (video-assisted thoracic surgery) in patients with completely resected NSCLC. PMID:22263005

  16. Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Cisplatin and Pemetrexed

    ClinicalTrials.gov

    2016-08-15

    Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Solid Neoplasm; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pleural Mesothelioma; Thymoma

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, 667-coumate, 9-aminocamptothecin; Ad5CMV-p53, AES-14, alefacept, anecortave acetate, APC-8024, APD-356, asoprisnil; Bevacizumab, bimakalim, bimatoprost, BLP-25, BR-1; Caspofungin acetate, cetuximab, cypher; Darbepoetin alfa, dexanabinol, dextromethorphan/quinidine sulfate, DNA.HIVA; Efaproxiral sodium, ertapenem sodium; Frovatriptan; HuMax-EGFr, HYB-2055, gamma-hydroxybutyrate sodium, Id-KLH vaccine, imatinib mesylate; Lapatinib, lonafarnib, Motexafin lutetium, MVA.HIVA, mycophenolic acid sodium salt; Nesiritide, NS-2330; Olmesartan medoxomil; Peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, perifosine, pimecrolimus, pregabalin; QbG-10; Ralfinamide, rasburicase, rFGF-2, Ro-31-7453; Sitaxsentan sodium, sorafenib; Tadalafil, TC-1734, telmisartan/hydrochlorothiazide, tenofovir disoproxil fumarate, thymus nuclear protein, tipifarnib; Vandetanib, vibriolysin, vildagliptin, voriconazole. PMID:15834466

  18. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, ademetionine, agalsidase alfa, agalsidase beta, alemtuzumab, alfimeprase, AMG-162, androgel, anidulafungin, antigastrin therapeutic vaccine, aripiprazole, atomoxetine hydrochloride; Bazedoxifene acetate, bevacizumab, bosentan; Caldaret hydrate, canfosfamide hydrochloride, choriogonadotropin alfa, ciclesonide, combretastatin A-4 phosphate, CY-2301; Darbepoetin alfa, darifenacin hydrobromide, decitabine, degarelix acetate, duloxetine hydrochloride; ED-71, enclomiphene citrate, eplerenone, epratuzumab, escitalopram oxalate, eszopiclone, ezetimibe; Fingolimod hydrochloride, FP-1096; HMR-3339A, HSV-TK/GCV gene therapy, human insulin, HuOKT3gamma1(Ala234-Ala235); Idursulfase, imatinib mesylate, indiplon, InnoVax C insulin glargine, insulin glulisine, irofulven; Labetuzumab, lacosamide, lanthanum carbonate, LyphoDerm, Lyprinol; Magnesium sulfate, metelimumab, methylphenidate hydrochloride; Natalizumab, NO-aspirin; OROS(R); PC-515, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, peptide YY3-36, posaconazole, pregabalin, PT-141, pyridoxamine; R-744, ramelteon, ranelic acid distrontium salt, rebimastat, repinotan hydrochloride, rhC1, rhGAD65, rosiglitazone maleate/metformin hydrochloride; Sardomozide, solifenacin succinate; Tadalafil, taxus, telavancin, telithromycin, tenofovir disoproxil fumarate, teriparatide, testosterone transdermal patch, tetomilast, tirapazamine, torcetrapib; Valspodar, vardenafil hydrochloride hydrate, vildagliptin; Yttrium Y90 epratuzumab; Ziprasidone hydrochloride. PMID:15672123

  19. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-05-01

    O(6)-Benzylguanine; (-)-Gossypol; Abatacept, AC-2592, Adalimumab, AIDSVAX gp120 B/E, Alemtuzumab, Aliskiren fumarate, ALVAC E120TMG, Ambrisentan, Amlodipine, Anakinra, Aripiprazole, Armodafinil, Atomoxetine hydrochloride, Avotermin; Bevacizumab, BIBW-2992, Bortezomib, Bosentan, Botulinum toxin type B; Canakinumab, CAT-354, Ciclesonide, CMV gB vaccine, Corifollitropin alfa, Daptomycin, Darbepoetin alfa, Dasatinib, Denosumab; EndoTAG-1, Eplerenone, Esomeprazole sodium, Eszopiclone, Etoricoxib, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; F-50040, Fesoterodine fumavate, Fondaparinux sodium, Fulvestrant; Gabapentin enacarbil, Golimumab; Imatinib mesylate, Inhalable human insulin, Insulin glargine, Ivabradine hydrochloride; Lercanidipine hydrochloride/enalapril maleate, Levosimendan, Liposomal vincristine sulfate, Liraglutide; MDV-3100, Mometasone furoate/formoterol fumavate, Multiepitope CTL peptide vaccine, Mycophenolic acid sodium salt, Nabiximols, Natalizumab, Nesiritide; Obeticholic acid, Olmesartan medoxomil, Omalizumab, Omecamtiv mecarbil; Paclitaxel-eluting stent, Paliperidone, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ ribavirin, Pemetrexed disodium, Polymyxin B nonapeptide, PORxin-302, Prasugrel, Pregabalin, Pridopidine; Ranelic acid distrontium salt, Rasagiline mesilate, rDEN4delta30-4995, Recombinant human relaxin H2, rhFSH, Rilonacept, Rolofylline, Rosiglitazone maleate/metformin hydrochloride, Rosuvastatin calcium, Rotigotine; Salcaprozic acid sodium salt, Sirolimus-eluting stent, Sitagliptin phosphate monohydrate, Sitaxentan sodium, Sorafenib, Sunitinib malate; Tadalafil, Tapentadol hydrochloride, Temsirolimus, Tenofovir, Tenofovir disoproxil fumarate, Teriparatide, Tiotropium bromide, Tocilizumab, Tolvaptan, Tozasertib, Treprostinil sodium; Ustekinumab; Vardenafil hydrochloride hydrate, Varenicline tartrate, Vatalanib succinate, Voriconazole, Vorinostat; Zotarolimus-eluting stent. PMID:20508873

  20. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-11-01

    1-Octanol, 9vPnC-MnCc; Abiraterone acetate, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, Aminolevulinic acid hexyl ester, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, Aripiprazole, ARRY-520, AS-1404, Asimadoline, Atazanavir sulfate, AVE-0277, Azelnidipine; Bevacizumab, Bimatoprost, Boceprevir, Bortezomib, Bosentan, Botulinum toxin type B; Certolizumab pegol, Cetuximab, Clevudine, Contusugene ladenovec, CP-751871, Crofelemer, Cypher, CYT006-AngQb; Darbepoetin alfa, Desmopressin, Dexlansoprazole, DG-041; E-5555, Ecogramostim, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Falecalcitriol, Fampridine, Fesoterodine fumarate, Fingolimod hydrochloride; Gefitinib, Ghrelin (human), GS-7904L, GV-1001; HT-1001; Insulin detemir, ISIS-112989, Istradefylline; Laquinimod sodium, Latanoprost/timolol maleate, Lenalidomide, Levobetaxolol hydrochloride, Liposomal doxorubicin, Liposomal morphine sulfate, Lubiprostone, Lumiracoxib, LY-518674; MEM-1003, Mesna disulfide, Mipomersen sodium, MM-093, Mycophenolic acid sodium salt; Naptumomab estafenatox, Natalizumab; Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paclitaxel nanoparticles, Paclitaxel poliglumex, Pasireotide, Pazufloxacin mesilate, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimagedine, Pimecrolimus, Pramlintide acetate, Prasterone, Pregabalin, Prulifloxacin; QAE-397; Rec-15/2615, RFB4(dsFv)-PE38, rhGAD65, Roflumilast, Romiplostim, Rosuvastatin calcium, Rotigotine, Rupatadine fumarate; Safinamide mesilate, SIR-Spheres, Sitagliptin phosphate, Sodium phenylacetate, Sodium phenylacetate/Sodium benzoate, Sorafenib, SSR-244738; Taribavirin hydrochloride, Taxus, Teduglutide, Tegaserod maleate, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tigecycline, Tiotropium bromide, Trabectedin, Travoprost

  1. Pemetrexed and bevacizumab-containing chemotherapy for pleomorphic carcinoma of the lung

    PubMed Central

    TAMURA, TOMOHIRO; OHARA, GEN; KAGOHASHI, KATSUNORI; KAWAGUCHI, MIO; KURISHIMA, KOICHI; SATOH, HIROAKI

    2016-01-01

    Pleomorphic carcinoma of the lung is a rare, highly malignant subtype of lung cancer, with a more aggressive clinical course compared with other types of non-small-cell lung cancer (NSCLC). Pemetrexed and bevacizumab are currently evaluated as two of the most reliable chemotherapeutic drugs for advanced NSCLC. We herein report a case of a 68- and a 46-year-old man with recurrent and chemo-naïve pleomorphic carcinoma of the lung, respectively, who were treated with a combination of carboplatin, pemetrexed and bevacizumab. The overall survival after the initiation of chemotherapy was 30 and 8 months, respectively. These cases exhibited a relatively long-term survival with chemotherapy. In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of this tumor, our cases demonstrated the potential utility of pemetrexed- and bevacizumab-containing chemotherapy. Our results also suggested that pemetrexed-containing chemotherapy may be key to the treatment of pleomorphic carcinoma of the lung. PMID:27073676

  2. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-04-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

  3. Identification of Up- and Down-Regulated Proteins in Pemetrexed-Resistant Human Lung Adenocarcinoma: Flavin Reductase and Calreticulin Play Key Roles in the Development of Pemetrexed-Associated Resistance.

    PubMed

    Chou, Hsiu-Chuan; Chen, Jing-Yi; Lin, Dai-Ying; Wen, Yueh-Feng; Lin, Chi-Chen; Lin, Sheng-Hao; Lin, Ching-Hsiung; Chung, Ting-Wen; Liao, En-Chi; Chen, Ying-Jen; Wei, Yu-Shan; Tsai, Yi-Ting; Chan, Hong-Lin

    2015-11-01

    Drug resistance is one of the major causes of cancer chemotherapy failure. In the current study, we used a pair of lung adenocarcinoma cell lines, A549 and the pemetrexed-resistant A549/PEM cells, as a model to monitor resistance-dependent cellular responses and identify potential therapeutic targets. By means of 2D differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), we investigated the global protein expression alterations induced by pemetrexed treatment and resistance. The proteomic result revealed that pemetrexed exposure obviously altered the expression of 81 proteins in the A549 cells, whereas no significant response was observed in the similarly treated A549/PEM cells, hence implying an association between these proteins and the drug-specific response. Moreover, 72 proteins including flavin reductase and calreticulin demonstrated differential expression between the A549 and A549/PEM cells, indicating baseline resistance. Additional tests employed siRNA silencing, protein overexpression, cell viability analysis, and analysis of apoptosis to examine and confirm the potency of flavin reductase and calreticulin proteins in the development of pemetrexed resistance. In summary, by using a proteomic approach, we identified numerous proteins, including flavin reductase and calreticulin, involved in pemetrexed drug resistance-developing mechanisms. Our results provide useful diagnostic markers and therapeutic candidates for pemetrexed-resistant lung cancer treatment. PMID:26452990

  4. Abnormal expression of PTEN and PIK3CA in pemetrexed-resistant human pancreatic cancer cell line Patu8988.

    PubMed

    Shi, X; Gu, H T; Lin, S B; Zhang, Y; Yang, J; Qian, C J

    2016-01-01

    The aim of this study was to investigate the expression of PTEN and PIK3CA in the pemetrexed-resistant human pancreatic cancer cell line Patu8988, and to evaluate their effects on the biological behavior of pancreatic cancer cells. PTEN and PIK3CA gene and protein expressions were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot, respectively, in a pemetrexed-resistant pancreatic cancer cell line and in the parent strain of the pancreatic cancer cells. The discrepancies between the two types of cell lines were detected by a transwell test. RT-PCR and western blot analyses revealed that PTEN and PIK3CA were overexpressed in the pemetrexed-resistant pancreatic cancer cell line. PTEN and PIK3CA were shown to be upregulated by 89 and 76% (western blot), respectively, in the pemetrexed-resistant cell line, compared to the normal pancreatic cancer cell line. The migratory and invasive abilities of the pemetrexed-resistant pancreatic cancer cell were significantly reduced compared to those of the parent strain (P < 0.05; transwell assay). Both PTEN and PIK3CA expression was abnormally enhanced in the pemetrexed-resistant cell line Patu8988; the co-existence of high levels of PTEN and PIK3CA in the pemetrexed-resistant pancreatic cancer line cells induced a significant decrease in their migratory and invasive capacities. This suggested that the mechanism of pemetrexed resistant may be affected by PTEN and PIK3CA, and that these may alter the biological behavior of cancer cells. PMID:27525871

  5. Molecular Resistance Fingerprint of Pemetrexed and Platinum in a Long-Term Survivor of Mesothelioma

    PubMed Central

    Røe, Oluf Dimitri; Szulkin, Adam; Anderssen, Endre; Flatberg, Arnar; Sandeck, Helmut; Amundsen, Tore; Erlandsen, Sten Even; Dobra, Katalin; Sundstrøm, Stein Harald

    2012-01-01

    Background Pemetrexed, a multi-folate inhibitor combined with a platinum compound is the first-line treatment of malignant mesothelioma, but median survival is still one year. Intrinsic and acquired resistance to pemetrexed is common, but its biological basis is obscure. Here we report for the first time a genome-wide profile of acquired resistance in the tumour from an exceptional case with advanced pleural mesothelioma and almost six years survival after 39 cycles of second-line pemetrexed/carboplatin treatment. Methodology and Principal Findings Genome-wide analysis with Illumina BeadChip Kit of 25,000 genes was performed on mRNA from pre-treatment and post-resistance biopsies from this individual as well on case and control samples from our previously published study (in total 17 samples). Cell specific expression of proteins encoded by selected genes were analysed by immunohistochemistry. Serial serum levels of CA125, CYFRA21-1 and SMRP levels were examined. TS protein, the main target of pemetrexed was overexpressed. Proteins and genes related to DNA damage response, elongation and telomere extension and repair related directly and indirectly to platinum resistance were overexpressed, as the CHK1 protein and the genes CHEK2, LIG3, POLD1, POLA2, FANCD2, PRPF19, RECQ5 respectively, the last two not previously described in mesothelioma. We observed a down-regulation of leukocyte transendothelial migration and cell adhesion molecules pathways. Silencing of NT5C in two mesothelioma cell lines did not sensitize the cells to Pemetrexed. Proposed resistance markers are TS, KRT7/ CK7, TYMP/ thymidine phosphorylase and down-regulated SPARCL1 and CDKN1B. Moreover, comparison of the primary expression of the sensitive versus a primary resistant case showed multi-fold overexpressed DNA repair, cell cycle, cytokinesis, and spindle formation in the latter. Serum CA125 and SMRP reflected the clinical and radiological course and tumour burden. Conclusions Genome

  6. Pemetrexed and gemcitabine as combination therapy for the treatment of Group3 medulloblastoma

    PubMed Central

    Morfouace, Marie; Shelat, Anang; Jacus, Megan; Freeman, Burgess B.; Turner, David; Robinson, Sarah; Zindy, Frederique; Wang, Yong-Dong; Finkelstein, David; Ayrault, Olivier; Bihannic, Laure; Li, Xiao-Nan; Olson, James M.; Robinson, Giles W.; Guy, R. Kiplin; Stewart, Clinton F.; Gajjar, Amar; Roussel, Martine F.

    2014-01-01

    SUMMARY We devised a high-throughput, cell-based assay to identify compounds to treat Group3 medulloblastoma (G3 MB). Mouse G3 MBs neurospheres were screened against a library of approximately 7,000 compounds including U.S. Food and Drug Administration (FDA)-approved drugs. We identified pemetrexed and gemcitabine that preferentially inhibited G3 MB proliferation in vitro compared to control neurospheres and substantially inhibited G3 MB proliferation in vivo. When combined, these two drugs significantly increased survival of mice bearing cortical implants of mouse and human G3 MBs that overexpress MYC compared to each agent alone, while having little effect on mouse MBs of the Sonic Hedgehog (SHH) subgroup. Our findings strongly suggest that combination therapy of pemetrexed and gemcitabine is a promising treatment for G3 MBs. PMID:24684846

  7. Pemetrexed plus dendritic cells as third-line therapy for metastatic esophageal squamous cell carcinoma

    PubMed Central

    Zhang, Bin; Li, Rui; Chang, Chun-Xiao; Han, Yong; Shi, Sheng-Bin; Tian, Jing

    2016-01-01

    This study was conducted to evaluate the toxicity and efficacy of pemetrexed plus dendritic cells (DCs) when administered as third-line treatment for metastatic esophageal squamous cell carcinoma (ESCC). All patients in the study group had previously failed first-line treatment with 5-fluorouracil and cisplatin-based regimens, as well as second-line treatment with taxane-based regimens. A total of 31 patients were treated with pemetrexed (500 mg/m2) plus DCs on day 1, every 3 weeks. DCs were given for one cycle of 21 days. Thirty patients were evaluated for their response. No patient had a complete response, three patients (10.0%) had a partial response, ten patients (33.3%) had stable disease, and 17 patients (56.7%) had progressive disease. The overall response rate was 10.0%. The median progression-free survival (PFS) time was 2.9 months (95% CI, 2.7–3.2), and the median overall survival (OS) time was 7.1 months (95% CI, 6.4–7.9). The median PFS and OS times among patients with high and low levels of miR-143 expression in their blood serum were significantly different: median PFS times =3.2 months (95% CI, 2.9–3.4) and 2.7 months (95% CI, 2.4–3.0), respectively (P=0.017), and median OS times =7.8 months (95% CI, 6.8–8.9) and 6.3 months (95% CI, 5.3–7.3), respectively (P=0.036). No patient experienced Grade 4 toxicity. Combined third-line treatment with pemetrexed and DCs was marginally effective and well tolerated in patients with advanced ESCC. Serum miR-143 levels are a potential biomarker for predicting the efficacy of pemetrexed plus DCs in the treatment of ESCC. PMID:27418834

  8. Monosodium glutamate, disodium inosinate, disodium guanylate, lysine and taurine improve the sensory quality of fermented cooked sausages with 50% and 75% replacement of NaCl with KCl.

    PubMed

    dos Santos, Bibiana Alves; Campagnol, Paulo Cezar Bastianello; Morgano, Marcelo Antônio; Pollonio, Marise Aparecida Rodrigues

    2014-01-01

    Fermented cooked sausages were produced by replacing 50% and 75% of NaCl with KCl and adding monosodium glutamate, disodium inosinate, disodium guanylate, lysine and taurine. The manufacturing process was monitored by pH and water activity measurements. The sodium and potassium contents of the resulting products were measured. The color values (L*, a* and b*), texture profiles and sensory profiles were also examined. Replacing 50% and 75% NaCl with KCl depreciated the sensory quality of the products. The reformulated sausages containing monosodium glutamate combined with lysine, taurine, disodium inosinate and disodium guanylate masked the undesirable sensory attributes associated with the replacement of 50% and 75% NaCl with KCl, allowing the production of fermented cooked sausages with good sensory acceptance and approximately 68% sodium reduction. PMID:24008059

  9. Comparison of erlotinib and pemetrexed as second-/third-line treatment for lung adenocarcinoma patients with asymptomatic brain metastases

    PubMed Central

    He, Yayi; Sun, Wenwen; Wang, Yan; Ren, Shengxiang; Li, Xuefei; Li, Jiayu; Rivard, Christopher J; Zhou, Caicun; Hirsch, Fred R

    2016-01-01

    Objective Brain metastases occur in one-third of all non-small-cell lung cancer patients. Due to restrictive transport at the blood–brain barrier, many drugs provide poor control of metastases in the brain. The aim of this study was to compare erlotinib with pemetrexed as second-/third-line treatment in patients with lung adenocarcinoma with asymptomatic brain metastases. Methods From January 2012 to June 2014, all lung adenocarcinoma patients with asymptomatic brain metastases who received treatment with erlotinib or pemetrexed as second-/third-line treatment were retrospectively reviewed. Chi-square and log-rank tests were used to perform statistical analysis. Results The study enrolled 99 patients, of which 44 were positive for EGFR mutation. Median progression-free survival (PFS) in months was not significantly different between the erlotinib- and pemetrexed-treated groups (4.2 vs 3.4 months; 95% confidence interval [CI]: 2.01–6.40 vs 2.80–5.00, respectively; P=0.635). Median PFS was found to be significantly longer in EGFR mutation–positive patients in the erlotinib-treated group (8.0 months; 95% CI 5.85–10.15) compared to the pemetrexed group (3.9 months; 95% CI: 1.25–6.55; P=0.032). The most common treatment-related side effect was mild-to-moderate rash and the most common drug-related side effects in the pemetrexed-group were vomiting and nausea. Conclusion Erlotinib and pemetrexed may be used as second-/third-line treatment in lung adenocarcinoma patients with asymptomatic brain metastases, and detection of EGFR mutation status is very important in these patients. EGFR mutation–positive lung adenocarcinoma patients with asymptomatic brain metastases showed longer PFS when treated with erlotinib as opposed to pemetrexed. PMID:27143936

  10. Uracil DNA glycosylase (UNG) loss enhances DNA double strand break formation in human cancer cells exposed to pemetrexed

    PubMed Central

    Weeks, L D; Zentner, G E; Scacheri, P C; Gerson, S L

    2014-01-01

    Misincorporation of genomic uracil and formation of DNA double strand breaks (DSBs) are known consequences of exposure to TS inhibitors such as pemetrexed. Uracil DNA glycosylase (UNG) catalyzes the excision of uracil from DNA and initiates DNA base excision repair (BER). To better define the relationship between UNG activity and pemetrexed anticancer activity, we have investigated DNA damage, DSB formation, DSB repair capacity, and replication fork stability in UNG+/+ and UNG−/− cells. We report that despite identical growth rates and DSB repair capacities, UNG−/− cells accumulated significantly greater uracil and DSBs compared with UNG+/+ cells when exposed to pemetrexed. ChIP-seq analysis of γ-H2AX enrichment confirmed fewer DSBs in UNG+/+ cells. Furthermore, DSBs in UNG+/+ and UNG−/− cells occur at distinct genomic loci, supporting differential mechanisms of DSB formation in UNG-competent and UNG-deficient cells. UNG−/− cells also showed increased evidence of replication fork instability (PCNA dispersal) when exposed to pemetrexed. Thymidine co-treatment rescues S-phase arrest in both UNG+/+ and UNG−/− cells treated with IC50-level pemetrexed. However, following pemetrexed exposure, UNG−/− but not UNG+/+ cells are refractory to thymidine rescue, suggesting that deficient uracil excision rather than dTTP depletion is the barrier to cell cycle progression in UNG−/− cells. Based on these findings we propose that pemetrexed-induced uracil misincorporation is genotoxic, contributing to replication fork instability, DSB formation and ultimately cell death. PMID:24503537

  11. Biliary Elimination of Pemetrexed Is Dependent on Mrp2 in Rats: Potential Mechanism of Variable Response in Nonalcoholic Steatohepatitis.

    PubMed

    Dzierlenga, Anika L; Clarke, John D; Klein, David M; Anumol, Tarun; Snyder, Shane A; Li, HongYu; Cherrington, Nathan J

    2016-08-01

    Hepatic multidrug resistance-associated protein 2 (MRP2) provides the biliary elimination pathway for many xenobiotics. Disruption of this pathway contributes to retention of these compounds and may ultimately lead to adverse drug reactions. MRP2 mislocalization from the canalicular membrane has been observed in nonalcoholic steatohepatitis (NASH), the late stage of nonalcoholic fatty liver disease, which is characterized by fat accumulation, oxidative stress, inflammation, and fibrosis. MRP2/Mrp2 mislocalization is observed in both human NASH and the rodent methionine and choline-deficient (MCD) diet model, but the extent to which it impacts overall transport capacity of MRP2 is unknown. Pemetrexed is an antifolate chemotherapeutic indicated for non-small cell lung cancer, yet its hepatobiliary elimination pathway has yet to be determined. The purpose of this study was to quantify the loss of Mrp2 function in NASH using an obligate Mrp2 transport substrate. To determine whether pemetrexed is an obligate Mrp2 substrate, its cumulative biliary elimination was compared between wild-type and Mrp2(-/-) rats. No pemetrexed was detected in the bile of Mrp2(-/-) rats, indicating pemetrexed is completely reliant on Mrp2 function for biliary elimination. Comparing the biliary elimination of pemetrexed between MCD and control animals identified a transporter-dependent decrease in biliary excretion of 60% in NASH. This study identifies Mrp2 as the exclusive biliary elimination mechanism for pemetrexed, making it a useful in vivo probe substrate for Mrp2 function, and quantifying the loss of function in NASH. This mechanistic feature may provide useful insight into the impact of NASH on interindividual variability in response to pemetrexed. PMID:27233293

  12. Disposition of disodium cromoglycate administered in three particle sizes.

    PubMed Central

    Curry, S H; Taylor, A J; Evans, S; Godfrey, S; Zeidifard, E

    1975-01-01

    1 Disodium cromoglycate (DSCG) was administered in three particle sizes to five human subjects. 2 Urinary excretion of DSCG, as a proportion of the dose, was highest following small particles; the lower values recorded following intermediate-sized and large particles were similar. 3 DSCG deposited in the mouth was highest following large particles; the lower values recorded following intermediate-sized and small particles were similar. 4 The data were examined in relation to the recent observation that the protective effect of small particles of DSCG is dramatically superior to that of large particles. PMID:825134

  13. Pharmacogenetics of pemetrexed combination therapy in lung cancer: pathway analysis reveals novel toxicity associations.

    PubMed

    Corrigan, A; Walker, J L; Wickramasinghe, S; Hernandez, M A; Newhouse, S J; Folarin, A A; Lewis, C M; Sanderson, J D; Spicer, J; Marinaki, A M

    2014-10-01

    Identification of polymorphisms that influence pemetrexed tolerability could lead to individualised treatment regimens and improve quality of life. Twenty-eight polymorphisms within eleven candidate genes were genotyped using the Illumina Human Exome v1.1 BeadChip and tested for their association with the clinical outcomes of non-small cell lung cancer and mesothelioma patients receiving pemetrexed/platinum doublet chemotherapy (n=136). GGH rs11545078 was associated with a reduced incidence of grade ⩾3 toxicity within the first four cycles of therapy (odds ratio (OR) 0.25, P=0.018), as well as reduced grade ⩾3 haematological toxicity (OR 0.13, P=0.048). DHFR rs1650697 conferred an increased risk of grade ⩾3 toxicity (OR 2.14, P=0.034). Furthermore, FOLR3 rs61734430 was associated with an increased likelihood of disease progression at mid-treatment radiological evaluation (OR 4.05, P=0.023). Polymorphisms within SLC19A1 (rs3788189, rs1051298 and rs914232) were associated with overall survival. This study confirms previous pharmacogenetic associations and identifies novel markers of pemetrexed toxicity. PMID:24732178

  14. Pemetrexed and its emerging role in the treatment of thoracic malignancies.

    PubMed

    Scagliotti, Giorgio V; Novello, Silvia

    2003-05-01

    Pemetrexed (Alimta); Eli Lilly and Co., Indianapolis, IN, USA) is a unique multitargeted antifolate that inhibits at least three enzymes, thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase. This novel drug is being evaluated in a comprehensive clinical programme for use in both front-line and second-line therapies. It has shown broad activity in a number of solid tumours, including colon cancer, breast cancer, lung cancer, head and neck, cervical cancer and others. While a number of antifolates have been evaluated in clinical trials, further development has been stopped or delayed by the occurrence of life-threatening toxicities. Similar trends were also initially observed with pemetrexed as well, but investigators later showed that these toxicities could be minimised with folic acid and vitamin B(12) supplementation included in the treatment regimen. Preliminary data indicate that this supplementation does not hamper drug efficacy in most tumour types and in many cases, supplemented patients exhibit improved clinical outcome. Here, the current data for pemetrexed in treating thoracic malignancies are reviewed, with special focus on malignant pleural mesothelioma and non-small cell lung cancer. PMID:12720495

  15. Influence of disodium EDTA on the nucleation and growth of struvite and carbonate apatite

    NASA Astrophysics Data System (ADS)

    Prywer, Jolanta; Olszynski, Marcin

    2013-07-01

    The effect of disodium EDTA, as an additive, on the crystallization of struvite and carbonate apatite was studied. The growth of struvite crystals and carbonate apatite occurred in the solution of artificial urine at 37 °C and at the condition emulating real urinary tract infection. The results demonstrate that the addition of disodium EDTA increases the induction time and decreases the growth efficiency compared to the baseline (without disodium EDTA). The struvite crystal mean and median diameters were found to decrease in the presence of disodium EDTA but the crystal morphology and habit remain almost unchanged. Disodium EDTA has demonstrated its potential to be further investigated in the presence of bacteria and in vivo conditions.

  16. SOCS-1 gene delivery cooperates with cisplatin plus pemetrexed to exhibit preclinical antitumor activity against malignant pleural mesothelioma.

    PubMed

    Iwahori, Kota; Serada, Satoshi; Fujimoto, Minoru; Ripley, Barry; Nomura, Shintaro; Mizuguchi, Hiroyuki; Shimada, Kazuki; Takahashi, Tsuyoshi; Kawase, Ichiro; Kishimoto, Tadamitsu; Naka, Tetsuji

    2013-01-15

    Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis for which an effective therapy remains to be established. This study investigated the therapeutic potential of gene delivery using suppressor of cytokine signaling 1 (SOCS-1), an endogenous inhibitor of intracellular signaling pathways, for the treatment of MPM. We infected MPM cells (MESO-4, H28 and H226) with adenovirus-expressing SOCS-1 vector to examine the effect of SOCS-1 overexpression on MPM cells. We evaluated the antitumor effect of SOCS-1 gene delivery combined with cisplatin plus pemetrexed by cell proliferation, apoptosis and invasion assay. We also investigated the regulation of NF-κB and STAT3 signaling related to apoptotic pathways. Furthermore, we evaluated the inhibition of tumor growth by SOCS-1 gene delivery combined with cisplatin plus pemetrexed in vivo. SOCS-1 gene delivery cooperated with cisplatin plus pemetrexed to inhibit cell proliferation, invasiveness and induction of apoptosis in MPM cells. SOCS-1 regulated NF-κB and STAT3 signaling to induce apoptosis in MESO-4 and H226 cells. Furthermore, SOCS-1 gene delivery cooperated with cisplatin plus pemetrexed to regulate NF-κB signaling and significantly inhibit tumor growth of MPM in vivo. These results suggest that SOCS-1 gene delivery has a potent antitumor effect against MPM and a potential for clinical use in combination with cisplatin plus pemetrexed. PMID:22532243

  17. Pemetrexed for advanced stage nonsquamous non-small cell lung cancer: latest evidence about its extended use and outcomes

    PubMed Central

    Tomasini, Pascale; Barlesi, Fabrice; Mascaux, Celine; Greillier, Laurent

    2016-01-01

    Non-small cell lung cancer (NSCLC) is still the leading cause of cancer-related death, and the treatment of advanced NSCLC relies on systemic treatments. During the last decade, pemetrexed, an antifolate agent, gradually became a key component of the treatment for patients with advanced nonsquamous NSCLC. It has indeed been shown to be efficient for first-line, maintenance and second- or third-line treatment in this subgroup of NSCLC. Moreover, it is usually well tolerated, with few grade 3 and 4 toxicities. Several studies have tried to identify predictive biomarkers of pemetrexed efficacy. Due to pemetrexed’s mechanism of action, thymidilate synthase expression predictive value was investigated but could not be demonstrated. Currently, more than 400 trials of pemetrexed for the treatment of nonsquamous NSCLC are ongoing. PMID:27239238

  18. Troubleshooting Arterial-Phase MR Images of Gadoxetate Disodium-Enhanced Liver

    PubMed Central

    Huh, Jimi; Yeh, Benjamin M.; Lee, Seung Soo; Kim, Kyoung Won; Wu, En-Haw; Wang, Z. Jane; Zhao, Li-qin; Chang, Wei Chou

    2015-01-01

    Gadoxetate disodium is a widely used magnetic resonance (MR) contrast agent for liver MR imaging, and it provides both dynamic and hepatobiliary phase images. However, acquiring optimal arterial phase images at liver MR using gadoxetate disodium is more challenging than using conventional extracellular MR contrast agent because of the small volume administered, the gadolinium content of the agent, and the common occurrence of transient severe motion. In this article, we identify the challenges in obtaining high-quality arterial-phase images of gadoxetate disodium-enhanced liver MR imaging and present strategies for optimizing arterial-phase imaging based on the thorough review of recent research in this field. PMID:26576109

  19. Pemetrexed downregulates ERCC1 expression and enhances cytotoxicity effected by resveratrol in human nonsmall cell lung cancer cells.

    PubMed

    Chen, Ruey-Shyang; Ko, Jen-Chung; Chiu, Hsien-Chun; Wo, Ting-Yu; Huang, Yi-Jhen; Tseng, Sheng-Chieh; Chen, Huang-Jen; Huang, Yu-Ching; Jian, Yi-Jun; Lee, Wei-Ting; Lin, Yun-Wei

    2013-12-01

    The multitargeted antifolate pemetrexed has demonstrated certain clinical activities against nonsmall cell lung cancer (NSCLC). Resveratrol (3,5,4-trihydroxy-trans-stilbene) is a polyphenol found in grapes and other plants and has great potential as a preventative and therapeutic agent due to its anticarcinogenic activity. The efficacy of adding resveratrol to pemetrexed to prolong the survival of patients with NSCLC still remains unclear. The excision repair cross-complementation 1 (ERCC1) is a DNA repair gene coding 5' endonuclease in nucleotide excision repair and is overexpressed in chemo- or radioresistant carcinomas. In this study, resveratrol (10-50 μM) inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with resveratrol increased ERCC1 messenger RNA and protein levels in a MKK3/6-p38 MAPK signal activation-dependent manner. Furthermore, blocking p38 MAPK activation by SB202190 or knocking down ERCC1 expression by transfection with small interfering RNA of ERCC1 enhanced the cytotoxicity of resveratrol. Combining resveratrol with pemetrexed resulted in a synergistic cytotoxic effect, accompanied with the reduction of phospho-p38 MAPK and ERCC1 protein levels, and a DNA repair capacity. Expression of constitutively active MKK6 (MKK6E) or HA-p38 MAPK vectors significantly rescued the decreased p38 MAPK activity, and restored ERCC1 protein levels and cell survival in resveratrol and pemetrexed cotreated NSCLC cells. In this study, for the first time, we have demonstrated the synergistic effect of combined treatment with resveratrol and pemetrexed in human NSCLC cells through downregulation of the MKK3/6-p38 MAPK-ERCC1 signal, suggesting a potential benefit of combining resveratrol and pemetrexed to treat lung cancer in the future. PMID:23912706

  20. Role of Gemcitabine and Pemetrexed as Maintenance Therapy in Advanced NSCLC: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Feng, Xuqin; Wen, Shimin; Fu, Xi; Guo, Cuihua; He, Wenwu

    2016-01-01

    Background Gemcitabine and pemetrexed have been used as maintenance therapy. However, few systematic reviews and meta-analyses have assessed their effects in the newest studies. This systematic review and meta-analysis were conducted to assess the role of gemcitabine and pemetrexed in the maintenance treatment of non-small-cell lung carcinoma (NSCLC). Methods We performed a literature search using PubMed, EMBASE and Cochrane library databases from their inceptions to September 16, 2015. We also searched the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and National Comprehensive Cancer Network (NCCN) databases from 2008 to 2015. Two authors independently extracted the data. The Cochrane Collaboration’s risk of bias graph was used to assess the risk of bias. The GRADE system was used to assess the grading of evidence, and a meta-analysis was conducted using Stata 11.0 software. Results Eleven randomized controlled trial (RCT) studies were collected. Ten studies were included in the meta-analysis and divided into the following 4 groups: gemcitabine vs. best supportive care (BSC)/observation, pemetrexed vs. BSC/placebo, pemetrexed + bevacizumab vs. bevacizumab and pemetrexed vs. bevacizumab. Gemcitabine exhibited significantly improved progression-free survival (PFS) compared with BSC (hazard ratio (HR) = 0.62, p = 0.000). Pemetrexed exhibited significantly improved PFS (HR = 0.54, p = 0.000) and OS (HR = 0.75, p = 0.000) compared with BSC. Pemetrexed + bevacizumab almost exhibited significantly improved PFS (HR = 0.71, p = 0.051) compared with bevacizumab. Pemetrexed exhibited no improvement in PFS or overall survival (OS) compared with bevacizumab. Regarding the grade, the GRADE system indicated that the gemcitabine group was "MODERATE", the pemetrexed group was "HIGH", and both the pemetrexed + bevacizumab vs. bevacizumab groups and pemetrexed vs. B groups were "LOW". Conclusions Gemcitabine or pemetrexed compared

  1. IDO Downregulation Induces Sensitivity to Pemetrexed, Gemcitabine, FK866, and Methoxyamine in Human Cancer Cells

    PubMed Central

    Maleki Vareki, Saman; Chen, Di; Di Cresce, Christine; Ferguson, Peter J.; Figueredo, Rene; Pampillo, Macarena; Rytelewski, Mateusz; Vincent, Mark; Min, Weiping; Zheng, Xiufen; Koropatnick, James

    2015-01-01

    Indoleamine 2,3-dioxygenase-1 (IDO) is an immune regulatory enzyme expressed by most human tumors. IDO levels in tumor cells correlate with increased metastasis and poor patient outcome and IDO is linked to tumor cell resistance to immunotherapy, radiation therapy, and chemotherapy. Knowledge of tumor cell-autonomous effects of IDO, independent of its well-known role in regulating and suppressing anti-tumor immune responses, is limited. Clonal populations of A549 human lung adenocarcinoma cells stably transfected with anti-IDO shRNA or scrambled control shRNA were used to study IDO effects on drug sensitivity and resistance. IFNγ was used to induce IDO in those cells. We show, for the first time, that IDO mediates human tumor cell resistance to the candidate anticancer drugs FK866 (an NAD+ inhibitor), methoxyamine (MX, a base excision repair [BER] inhibitor) and approved anticancer drugs pemetrexed (a folate anti-metabolite) and gemcitabine (a nucleoside analogue), and combined treatment with pemetrexed and MX, in the absence of immune cells. Concurrent knockdown of IDO and thymidylate synthase (TS, a key rate-limiting enzyme in DNA synthesis and repair) sensitizes human lung cancer cells to pemetrexed and 5FUdR to a greater degree than knockdown of either target alone. We conclude that BER in IDO-expressing A549 cells plays a major role in mediating resistance to a range of approved and candidate anticancer drugs. IDO inhibitors are undergoing clinical trials primarily to improve antitumor immune responses. We show that targeting IDO alone or in combination with TS is a potentially valuable therapeutic strategy for cancer treatment, independent of immune activity and in combination with conventional chemotherapy. PMID:26579709

  2. Mobilization and redistribution of lead over the course of calcium disodium ethylenediamine tetraacetate chelation therapy

    SciTech Connect

    Cory-Slechta, D.A.; Weiss, B.; Cox, C.

    1987-12-01

    After its successful application to the treatment of acute Pb poisoning, Ca disodium EDTA came into routine clinical use for diagnosis and treatment of subacute and chronic Pb poisoning. Despite widespread use, few definitive conclusions have emerged about the sources of Pb mobilized by Ca disodium EDTA. Furthermore, the possibility that mobilized Pb may be redistributed has been suggested. The current studies indicate that the standard therapeutic protocol for Ca disodium EDTA has little impact on critical organs such as brain and liver and moreover, that diagnostic Ca disodium EDTA chelation may even increase the concentration of Pb in these tissues. After a 3 to 4 month exposure to Pb acetate in drinking water, different groups of rats received daily i.p. injections of saline (control), 75 or 150 mg/kg of Ca disodium EDTA for either 1, 2, 3, 4 or 5 days and were then sacrificed 24 hr after the final injection. Tissue analyses indicated that Pb was mobilized from bone and kidney and redistributed initially to both brain and liver. Levels in both brain and liver declined with subsequent Ca disodium EDTA injections, but no net loss from either tissue occurred over the 5-day treatment period despite a decline in blood Pb levels and a marked enhancement of urinary Pb excretion. These findings stress the need for further investigation of Ca disodium EDTAs effects and for parallel evaluation of alternate chelating agents, and suggest that a re-evaluation of both the diagnostic and therapeutic roles of Ca disodium EDTA may be advisable.

  3. Efficacy of pemetrexed-based regimen in relapsed advanced thymic epithelial tumors and its association with thymidylate synthetase level

    PubMed Central

    Qian, Xinyu; Song, Zhengbo

    2016-01-01

    Purpose Due to the rarity of thymic epithelial tumors (TET), no standard chemotherapy regimen has been identified in the relapsed setting. The aim of this study was to investigate the activity of a pemetrexed-based regimen in advanced TET as palliative treatment after failure of previous chemotherapy, and to detect its association with thymidylate synthetase (TS) level. Methods Patients with pathologically confirmed TET and treated with pemetrexed-based regimen were evaluated from 2006 to 2014 in Zhejiang Cancer Hospital. TS mRNA level was detected by real-time polymerase chain reaction. The Kaplan–Meier method was used for survival analysis. Results A total of 22 TET patients were identified, of whom eight had thymoma and 14 had thymic carcinoma. In total, the objective response rate and disease control rate of the 22 patients were 22.7% and 68.2%, respectively. Median progression-free survival and overall survival were 4.5 months and 34.9 months, respectively. A trend of lower TS mRNA levels existed in patients with disease control compared to those with progressive disease (268.0±160.5×10−4 vs 567.0±445.0×10−4, P=0.065). Conclusion Patients with advanced TET may benefit from pemetrexed-based regimen therapy. TS mRNA level is valuable for predicting the efficacy of pemetrexed in TET. PMID:27524908

  4. Synergistic effects of sorafenib in combination with gemcitabine or pemetrexed in lung cancer cell lines with K-ras mutations

    PubMed Central

    Wang, Shu; Su, Zeng-feng; Yuan, Yuan

    2016-01-01

    K-ras is currently accepted as the most frequently mutated oncogene in non-small cell lung cancer (NSCLC, including squamous carcinoma, adenocarcinoma, and large cell carcinoma). NSCLC patients with the K-ras mutation appear to be refractory to the majority of systemic therapies. In the present study, the in vitro antitumor effects and correlated molecular mechanisms of sorafenib combined with gemcitabine or pemetrexed were explored in the K-ras mutation-positive NSCLC A549 cell line. Sorafenib was seen to exhibit dose-dependent growth inhibition in the A549 cells, while sorafenib combined with pemetrexed demonstrated a greater synergism compared with sorafenib combined with gemcitabine. Sorafenib arrested the cell cycle at the G1 phase, while gemcitabine and pemetrexed caused arrest at the S phase. The molecular mechanism of this synergism was due to the downstream signalling pathways, which were efficiently suppressed by sorafenib, therefore increasing the incidence of the entry of the chemotherapeutic drugs into the apoptotic pathways. Moreover, sorafenib and pemetrexed demonstrated stronger synergism, demonstrating that inhibiting the Ras/Raf/Mek/Erk and Ras/PI3K/Akt pathways concurrently may achieve improved antitumor effects. PMID:27095937

  5. Fospropofol Disodium for Sedation in Elderly Patients Undergoing Flexible Bronchoscopy

    PubMed Central

    Silvestri, Gerard A.; Vincent, Brad D.; Wahidi, Momen M.

    2011-01-01

    Background Fospropofol disodium is a water-soluble prodrug of propofol. A subset analysis was undertaken of elderly patients (≥65 y) undergoing flexible bronchoscopy, who were part of a larger multicenter, randomized, double-blind study. Methods Patients received fentanyl citrate (50 mcg) followed by fospropofol at initial (4.88mg/kg) and supplemental (1.63mg/kg) doses. The primary end point was sedation success (3 consecutive Modified Observer's Assessment of Alertness/Sedation scores of ≤4 and procedure completion without alternative sedative or assisted ventilation). Treatment success, time to fully alert, patient and physician satisfaction, and safety/tolerability were also evaluated. Results In the elderly patients subset (n=61), sedation success was 92%, the mean time to fully alert was 8.0±10.9 min, and memory retention was 72% during recovery, and these were comparable with the younger patients subgroup (age, <65 y). Sedation-related adverse events occurred in 23% of the elderly and 18% of the younger patients (age, <65 y) group. Hypoxemia occurred in 26% of the elderly and 18% of the younger patients group, but no escalation of care was required. Conclusions Fospropofol provided safe and effective sedation, rapid time to fully alert, and high satisfaction in this elderly subset undergoing flexible bronchoscopy, which was comparable with outcomes in younger patients. PMID:21701693

  6. Combretastatin A4 disodium phosphate-induced myocardial injury

    PubMed Central

    Tochinai, Ryota; Nagata, Yuriko; Ando, Minoru; Hata, Chie; Suzuki, Tomo; Asakawa, Naoyuki; Yoshizawa, Kazuhiko; Uchida, Kazumi; Kado, Shoichi; Kobayashi, Toshihide; Kaneko, Kimiyuki; Kuwahara, Masayoshi

    2016-01-01

    Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). The results revealed multifocal myocardial necrosis with a predilection for the interventricular septum and subendocardial regions of the apex of the left ventricular wall, injury of capillaries, morphological change of the ST junction, and QT interval prolongation. The histopathological profile of myocardial lesions suggested that CA4DP induced a lack of myocardial blood flow. CA4DP increased the diastolic BP and showed direct effects on hiPS-CMs. These results suggest that CA4DP induces dysfunction of small arteries and capillaries and has direct toxicity in cardiomyocytes. Therefore, it is thought that CA4DP induced capillary and myocardial injury due to collapse of the microcirculation in the myocardium. Moreover, the direct toxic effect of CA4DP on cardiomyocytes induced myocardial lesions in a coordinated manner.

  7. Combretastatin A4 disodium phosphate-induced myocardial injury.

    PubMed

    Tochinai, Ryota; Nagata, Yuriko; Ando, Minoru; Hata, Chie; Suzuki, Tomo; Asakawa, Naoyuki; Yoshizawa, Kazuhiko; Uchida, Kazumi; Kado, Shoichi; Kobayashi, Toshihide; Kaneko, Kimiyuki; Kuwahara, Masayoshi

    2016-07-01

    Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). The results revealed multifocal myocardial necrosis with a predilection for the interventricular septum and subendocardial regions of the apex of the left ventricular wall, injury of capillaries, morphological change of the ST junction, and QT interval prolongation. The histopathological profile of myocardial lesions suggested that CA4DP induced a lack of myocardial blood flow. CA4DP increased the diastolic BP and showed direct effects on hiPS-CMs. These results suggest that CA4DP induces dysfunction of small arteries and capillaries and has direct toxicity in cardiomyocytes. Therefore, it is thought that CA4DP induced capillary and myocardial injury due to collapse of the microcirculation in the myocardium. Moreover, the direct toxic effect of CA4DP on cardiomyocytes induced myocardial lesions in a coordinated manner. PMID:27559241

  8. Columnar molecular aggregation in the aqueous solutions of disodium cromoglycate

    NASA Astrophysics Data System (ADS)

    Agra-Kooijman, Dena M.; Singh, Gautam; Lorenz, Alexander; Collings, Peter J.; Kitzerow, Heinz-S.; Kumar, Satyendra

    2014-06-01

    Stack, chimneylike, and threadlike assemblies have previously been proposed for the structure of disodium cromoglycate (DSCG) aggregates in aqueous solutions. The results of the synchrotron x-ray scattering investigations reported here reveal the formation of simple columnar assemblies with π-π stacking at a separation of 3.4 Å between the DSCG molecules. Lateral separation between the assemblies is concentration and temperature dependent, varying from ˜35 to 42 Å in the orientationally ordered nematic (N) phase and from 27 to 32 Å in the columnar or middle (M) phase having long range lateral positional order. The assemblies' length depends on concentration and consists of ˜23 molecules in the N phase, becoming three to ten times larger in the M phase. The scission energy is concentration dependent in the N phase with values ˜7.19 ± 0.14 kBT (15 wt %), 2.73 ± 0.4 kBT (20 wt %), and 3.05 ± 0.2 kBT (25 wt %). Solutions of all concentrations undergo a spinodal decomposition at temperatures above ˜40 °C, resulting in DSCG-rich regions with the M phase and water-rich regions in the N and isotropic phases.

  9. Columnar molecular aggregation in the aqueous solutions of disodium cromoglycate.

    PubMed

    Agra-Kooijman, Dena M; Singh, Gautam; Lorenz, Alexander; Collings, Peter J; Kitzerow, Heinz-S; Kumar, Satyendra

    2014-06-01

    Stack, chimneylike, and threadlike assemblies have previously been proposed for the structure of disodium cromoglycate (DSCG) aggregates in aqueous solutions. The results of the synchrotron x-ray scattering investigations reported here reveal the formation of simple columnar assemblies with π-π stacking at a separation of 3.4 Å between the DSCG molecules. Lateral separation between the assemblies is concentration and temperature dependent, varying from ∼35 to 42 Å in the orientationally ordered nematic (N) phase and from 27 to 32 Å in the columnar or middle (M) phase having long range lateral positional order. The assemblies' length depends on concentration and consists of ∼23 molecules in the N phase, becoming three to ten times larger in the M phase. The scission energy is concentration dependent in the N phase with values ∼7.19 ± 0.14 k_{B}T (15 wt %), 2.73 ± 0.4 k_{B}T (20 wt %), and 3.05 ± 0.2 k_{B}T (25 wt %). Solutions of all concentrations undergo a spinodal decomposition at temperatures above ∼40 °C, resulting in DSCG-rich regions with the M phase and water-rich regions in the N and isotropic phases. PMID:25019802

  10. Glucocorticoid Receptor Status is a Principal Determinant of Variability in the Sensitivity of Non-Small Cell Lung Cancer Cells to Pemetrexed

    PubMed Central

    Patki, Mugdha; Gadgeel, Shirish; Huang, Yanfang; McFall, Thomas; Shields, Anthony F.; Matherly, Larry H.; Bepler, Gerold; Ratnam, Manohar

    2014-01-01

    Introduction Pemetrexed is an S-phase targeted drug in front-line or maintenance therapy of advanced non-squamous non-small cell lung cancer (NSCLC) but methods are needed for predicting the drug response. Dexamethasone is typically administered the day before, the day of and the day after pemetrexed. As dexamethasone strongly regulates many genes including p53 through the glucocorticoid receptor (GR), we hypothesized that dexamethasone influences tumor response to pemetrexed. Methods Eight non-squamous NSCLC cell line models with varied p53 and GRα/GRβ status were used for gene expression and cell cycle analyses and for loss/gain-of-function experiments. Results In three cell lines dexamethasone profoundly, but reversibly, suppressed the fraction of S-phase cells. Dexamethasone also reversibly repressed expression of thymidylate synthase and dihydrofolate reductase which are primary targets of pemetrexed but are also quintessential S-phase enzymes as well as the S-phase dependent expression of thymidine kinase 1. Dexamethasone also decreased expression of the major pemetrexed transporters, the reduced folate carrier and the proton coupled folate transporter. Only cells expressing relatively high GRα showed these dexamethasone effects, regardless of p53 status. In cells expressing low GRα, the dexamethasone response was rescued by ectopic GRα. Further, depletion of p53 did not attenuate the dexamethasone effects. The presence of dexamethasone during pemetrexed treatment protected against pemetrexed cytotoxicity, in only the dexamethasone responsive cells. Conclusions The results predict that in non-squamous NSCLC tumors, reversible S-phase suppression by dexamethasone, possibly combined with a reduction in the drug transporters, attenuates responsiveness to pemetrexed and that GR status is a principal determinant of tumor variability of this response. PMID:24736075

  11. Successful pemetrexed-containing chemotherapy for epidermal growth factor receptor mutation-positive adenosquamous cell carcinoma of the lung: A case report

    PubMed Central

    WATANABE, HIROKO; TAMURA, TOMOHIRO; KAGOHASHI, KATSUNORI; KAWAGUCHI, MIO; KURISHIMA, KOICHI; SATOH, HIROAKI

    2016-01-01

    Pemetrexed-containing chemotherapy has shown promise in the treatment of non-small-cell lung cancer (NSCLC). However, although adenosquamous cell lung cancer (ASCLC) is a type of NSCLC, the availability of studies investigating its response to pemetrexed-containing chemotherapy is limited. A 66-year-old woman was referred to Mito Medical Center, University of Tsukuba with hemoptysis and a chest computed tomography (CT) scan revealed a large cavitary mass in the lower lobe of the left lung. The patient underwent left lower lobectomy and mediastinal lymph node dissection. The tumor was staged as pT2bN2M0. An epidermal growth factor receptor (EGFR) exon 19 deletion was identified in the adenocarcinomatous as well as the squamous cell carcinomatous components. Despite gefitinib therapy for pulmonary metastases, the patient developed cavitary metastases in both lungs. Therefore, treatment with pemetrexed-containing chemotherapy was initiated. A chest CT scan revealed significant regression of the metastatic lesions in both lungs, with thinning of the walls. The patient remains well and recurrence-free 19 months after the initiation of pemetrexed-containing chemotherapy. Therefore, the clinical response of EGFR mutation-positive ASCLC to pemetrexed-containing chemotherapy was promising, suggesting pemetrexed to be one of the key drugs for this subset of ASCLC patients. PMID:27073680

  12. Role of pemetrexed in advanced non-small-cell lung cancer: meta-analysis of randomized controlled trials, with histology subgroup analysis

    PubMed Central

    Al-Saleh, K.; Quinton, C.; Ellis, P.M.

    2012-01-01

    Purpose Platinum-based regimens represent the standard first-line treatment for non-small-cell lung cancer (nsclc). However, newer data have established a role for pemetrexed in the treatment of this disease. Such data suggest that histology represents a determining factor in the selection of treatment. Methods We undertook a systematic review of the literature for randomized controlled trials that compared the efficacy of pemetrexed with that of other treatments in advanced nsclc. Data and study quality were assessed according to published guidelines. Results We identified five trials that compared pemetrexed with other treatments or with placebo. Overall survival for patients treated with pemetrexed was superior to that with other treatments: hazard ratio (hr): 0.89; 95% confidence interval (ci): 0.80 to 0.99. The survival benefit was limited to patients with non-squamous histology: hr: 0.82; 95% ci: 0.73 to 0.91. Pemetrexed was inferior to other chemotherapy options in patients with squamous histology: hr: 1.19; 95% ci: 0.99 to 1.43. Conclusions Compared with other chemotherapy agents, pemetrexed is more effective for the treatment of nsclc in patients with non-squamous histology. PMID:22328848

  13. Preclinical emergence of vandetanib as a potent antitumour agent in mesothelioma: molecular mechanisms underlying its synergistic interaction with pemetrexed and carboplatin

    PubMed Central

    Giovannetti, E; Zucali, P A; Assaraf, Y G; Leon, L G; Smid, K; Alecci, C; Giancola, F; Destro, A; Gianoncelli, L; Lorenzi, E; Roncalli, M; Santoro, A; Peters, G J

    2011-01-01

    Background: Although pemetrexed, a potent thymidylate synthase (TS) inhibitor, enhances the cytoytoxic effect of platinum compounds against malignant pleural mesothelioma (MPM), novel combinations with effective targeted therapies are warranted. To this end, the current study evaluates new targeted agents and their pharmacological interaction with carboplatin–pemetrexed in human MPM cell lines. Methods: We treated H2052, H2452, H28 and MSTO-211H cells with carboplatin, pemetrexed and targeted compounds (gefitinib, erlotinib, sorafenib, vandetanib, enzastaurin and ZM447439) and evaluated the modulation of pivotal pathways in drug activity and cancer cell proliferation. Results: Vandetanib emerged as the compound with the most potent cytotoxic activity, which interacted synergistically with carboplatin and pemetrexed. Drug combinations blocked Akt phosphorylation and increased apoptosis. Vandetanib significantly downregulated epidermal growth factor receptor (EGFR)/Erk/Akt phosphorylation as well as E2F-1 mRNA and TS mRNA/protein levels. Moreover, pemetrexed decreased Akt phosphorylation and expression of DNA repair genes. Finally, most MPM samples displayed detectable levels of EGFR and TS, the variability of which could be used for patients' stratification in future trials with vandetanib–pemetrexed–carboplatin combination. Conclusion: Vandetanib markedly enhances pemetrexed–carboplatin activity against human MPM cells. Induction of apoptosis, modulation of EGFR/Akt/Erk phosphorylation and expression of key determinants for pemetrexed and carboplatin activity contribute to this synergistic interaction, and, together with the expression of these determinants in MPM samples, warrant further clinical investigation. PMID:21970874

  14. Crocin inhibits cell proliferation and enhances cisplatin and pemetrexed chemosensitivity in lung cancer cells

    PubMed Central

    Chen, Shuangshuang; Zhao, Shuang; Wang, Xinxing; Zhang, Luo; Jiang, Enze; Gu, Yuan; Shangguan, Anna Junjie; Zhao, Hong

    2015-01-01

    Background Crocin is the major constituent of saffron, a naturally derived Chinese medicine obtained from the dried stigma of the Crocus sativus flower. It has a variety of pharmacological effects, including anti-oxidative, immunity enhancement, and anti-tumorigenic properties; however, the molecular mechanisms underlying these effects remain unknown. Methods To investigate the effects of crocin on proliferation and apoptosis of lung adenocarcinoma cells, lung adenocarcinoma cell lines, A549 and SPC-A1, were treated with crocin at different dosages. Cell morphological changes were observed by light microscopy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the inhibitory effect of crocin on cell proliferation and sensitivity to chemotherapeutic drugs. Flow cytometry was used to characterize cell apoptosis and cell cycle profiles. Reverse transcription-polymerase chain reaction was used to detect mRNA levels of apoptosis-related genes. Results Crocin inhibited cell proliferation and induced apoptosis in A549 and SPC-A1 cells in a concentration-dependent manner, accompanied with an increase of G0/G1 arrest. Crocin significantly increased the mRNA levels of both p53 and B-cell lymphoma 2-associated X protein (Bax), while decreasing B-cell lymphoma 2 (Bcl-2) mRNA expressions. In addition, crocin combined with either cisplatin or pemetrexed showed additive effects on cell proliferation in two lung cancer cell lines. Conclusions Crocin significantly suppressed the proliferation of human lung adenocarcinoma cells and enhanced the chemo sensitivity of these cells to both cisplatin and pemetrexed. The actions of molecular mechanism could be through the induction of cell cycle arrest and apoptosis by p53 and Bax up-regulation but Bcl-2 down-regulation. PMID:26798587

  15. Simple spectrophotometric method for estimation of disodium edetate in topical gel formulations

    PubMed Central

    Kamboj, Sunil; Sharma, Deepak; Nair, Anroop B.; Kamboj, Suman; Sharma, Rakesh Kumar; Ali, Javed; Pramod, K; Ansari, S. H.

    2011-01-01

    A simple, sensitive, cost-effective and reproducible UV-spectrophotometric method has been developed and validated for the estimation of disodium edetate in topical gel formulations. Solution of disodium edetate reacts with ferric chloride to form complex in 0.1 N HCl giving λmax at 270 nm. Beer's law was obeyed in the concentration range of 5–50 μg/mL (r2= 0.9997). The limit of detection and limit of quantitation were found to be 1.190 and 3.608 μg/mL, respectively. The results show that the procedure is accurate, precise, and reproducible (relative standard deviation < 1%), while being simple and less time consuming. The study concluded that the UV-spectrophotometric method could be used for the quantification of disodium edetate in pure form as well as in pharmaceutical formulations. PMID:23781446

  16. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide

  17. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-03-01

    ABT-869, Acadesine, Acetylsalicylic acid/omeprazole, Adefovir, Adefovir dipivoxil, AEG-35156, Agatolimod sodium, Albiglutide, Alemtuzumab, Alipogene tiparvovec, Alogliptin benzoate, AMG-386, Amrubicin hydrochloride, Apremilast, Aripiprazole, Asoprisnil, Atorvastatin/fenofibrate, AVN-944, Axitinib; Belinostat, Bevacizumab, BHT-3021, BI-2536, Biapenem, Bilastine, Biphasic insulin aspart, Blinatumomab, Bortezomib, Bosentan; Catumaxomab, CD-NP, Cediranib, Certolizumab pegol, Cetuximab, Choline fenofibrate, Ciclesonide, CK-1827452,Clevudine, Clofarabine, CSL-360, CYT-997; Dapagliflozin, Darinaparsin, Denosumab, Densiron 68, Desloratadine, Dulanermin; Edoxaban tosilate, Emtricitabine, Entecavir, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fidaxomicintiacumiv, Fulvestrant; G-207, GCR-8015, Gefitinib, Ghrelin (human), Glufosfamide; HPV16L1E7CVLP; Ibutamoren mesilate, Imatinib mesylate, Insulin detemir, Insulin glargine, Iodine (I131) tositumomab, Istaroxime, ITMN-191, Ixabepilone; JZP-4, Lenalidomide; Levetiracetam, Linaclotide acetate, Liposomal cytarabine/daunorubicin, Liposomal doxorubicin, Liraglutide, LY-518674; Milatuzumab, MMR-V, Motesanib diphosphate, Mycophenolic acid sodium salt; Niacin/simvastatin; Obatoclax mesylate, Odanacatib; Paclitaxel nanoparticles, Paclitaxel-eluting stent, Pazufloxacin, PBT-2, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pemetrexed disodium, Perampanel, PfCP2.9, Pitavastatin calcium, Poly I:CLC, Pomalidomide, Pralatrexate, Pramlintide acetate, Prucalopride; rhGAD65, Roflumilast; RTS,S/AS02D; SCH-530348, Semagacestat, Sirolimus-eluting coronary stent, Sirolimus-Eluting Stent, SIR-Spheres, Sivelestat sodium hydrate, Sorafenib, Sunitinib malate; Tadalafil, Tafluprost, Tanespimycin, Teduglutide, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tiotropium bromide, TMC-435350, Tositumomab/iodine (I131) tositumomab, Travoprost/timolol, Triciribine

  18. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 166Ho-DOTMP, 3-AP; Abatacept, abetimus sodium, ACR-16, adefovir dipivoxil, alefacept, AMD-070, aminolevulinic acid hexyl ester, anatumomab mafenatox, anti-CTLA-4 MAb, antigastrin therapeutic vaccine, AP-12009, AP-23573, APC-8024, aripiprazole, ATL-962, atomoxetine hydrochloride; Bevacizumab, bimatoprost, bortezomib, bosentan, BR-1; Calcipotriol/betamethasone dipropionate, cinacalcet hydrochloride, clofazimine, colchicine, cold-adapted influenza vaccine trivalent, CRM197; Desloratadine, desoxyepothilone B, diethylhomospermine; Edodekin alfa, efalizumab, elcometrine, eletriptan, enfuvirtide, entecavir, EP-2101, eplerenone, erlotinib hydrochloride, etoricoxib, everolimus, exherin, ezetimibe; Febuxostat, fluorescein lisicol, fosamprenavir calcium, frovatriptan; Hemoglobin raffimer, HSPPC-96, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, IRX-2, istradefylline, IV gamma-globulin, ixabepilone; Kahalalide F; L-759274, levodopa/carbidopa/entacapone, licofelone, lonafarnib, lopinavir, lurtotecan, LY-156735; MAb G250, mecasermin, melatonin, midostaurin, muraglitazar; Nesiritide, nitronaproxen; O6-Benzylguanine, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, omapatrilat, oral insulin; Parecoxib sodium, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, peptide YY3-36, PG-CPT, phenoxodiol, pimecrolimus, posaconazole; Rasagiline mesilate, rDNA insulin, RG228, rimonabant hydrochloride, rosuvastatin calcium, rotigotine hydrochloride; S-3304, safinamide mesilate, salcaprozic acid sodium salt, SDZ-SID-791, SGN-30, soblidotin

  19. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-04-01

    (+)-Dapoxetine hydrochloride, [(123)I]-BZA, 9-Aminocamptothecin; Abacavir sulfate/lamivudine, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Alvocidib hydrochloride, Ambrisentan, Amsilarotene, Anacetrapib, Anakinra, Apricitabine, Aripiprazole, Arsenic trioxide, Atazanavir sulfate, Atazanavir/ritonavir, Atrasentan, Azacitidine; Banoxantrone, Bazedoxifene acetate, Bevacizumab, Bexarotene, Biphasic insulin aspart, Bortezomib, Bosentan, Bromfenac; Cachectin, Calcipotriol/betamethasone dipropionate, Canakinumab, Carfilzomib, CAT-354, CCX-282, Certolizumab pegol, Cetuximab, Choline fenofibrate, Clevudine, Clofarabine, CNTO-328, Corifollitropin alfa, Crofelemer; Daptomycin, Darbepoetin alfa, Darunavir, Dasatinib, Decitabine, Deferasirox, Denosumab, Duloxetine hydrochloride, Dutasteride; Emtricitabine, Enfuvirtide, Entecavir, Epoetin zeta, Erlotinib hydrochloride, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Farglitazar, Febuxostat, Fosamprenavir calcium, FX-06; Gabapentin enacarbil, Gefitinib; HIVIS DNA; Imatinib mesylate, INCB- 18424, Indacaterol, Inotuzumab ozogamicin, Insulin detemir; JNJ-26854165; Lacosamide, Landiolol, Laromustine, Lenalidomide, Liposomal doxorubicin, L-NAME, Lopinavir, Lopinavir/ritonavir, Lumiracoxib; Maraviroc, Mepolizumab, Methoxy polyethylene glycol- epoetin-beta, Miglustat, MK-0493, MVA-CMDR, Mycophenolic acid sodium salt; Natalizumab, Nepafenac, Neratinib, Neridronic acid, Nesiritide, Nilotinib hydrochloride monohydrate; Olmesartan medoxomil, Omacetaxine mepesuccinate, Omalizumab; Paclitaxel poliglumex, Palifermin, Patupilone, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ ribavirin, Pemetrexed disodium, PHA-848125, Pitavastatin calcium, Posaconazole, Povidone-iodine liposome complex, Prasugrel, Pregabalin, Prucalopride; Raltegravir potassium, Retigabine, Revaprazan hydrochloride, rhFSH, Rilpivirine, Rivaroxaban, Romidepsin

  20. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, Ad5CMV-p53, adefovir dipivoxil, AE-941, ambrisentan, aripiprazole, atomoxetine hydrochloride, atrasentan; BCH-10618, bimatoprost, BMS-184476, BMS-275183, BMS-387032, botulinum toxin type B, BR-1, BR96-Doxorubicin; Capravirine, caspofungin acetate, cinacalcet hydrochloride; Darbepoetin alfa, desloratadine, dextrin sulfate, DJ-927, duloxetine hydrochloride; Elacridar, emtricitabine, eplerenone, ertapenem sodium, escitalopram oxalate, ESP-24217, etoricoxib, exenatide, ezetimibe; Ferumoxtran-10, fondaparinux sodium, fosamprenavir calcium; GS-7904L, GW-5634; HMN-214, human insulin; IC-14, imatinib mesylate, indiplon, insulin glargine, insulinotropin, iseganan hydrochloride; Lanthanum carbonate, L-Arginine hydrochloride, LEA29Y, lenalidomide, LE-SN38, lestaurtinib, L-MDAM, lometrexol, lopinavir, lopinavir/ritonavir; Magnesium sulfate, maraviroc, mepolizumab, metreleptin, milataxel, MNA-715, morphine hydrochloride; Nesiritide, neutrophil-inhibitory factor, NK-911; Olanzapine/fluoxetine hydrochloride, olmesartan medoxomil, omalizumab, ortataxel, oxycodone hydrochloride/ibuprofen; Panitumumab, patupilone, PC-515, PD-MAGE-3 Vaccine, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, pimecrolimus, prasugrel, pregabalin, PRO-2000; Rosuvastatin calcium, RPR-113090; sabarubicin hydrochloride, safinamide mesilate, SB-715992, sitaxsentan sodium, soblidotin, synthadotin; Tadalafil, taltobulin, temsirolimus, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, testosterone gel, tigecycline, tipranavir, tirapazamine, trabectedin

  1. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b

  2. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort

  3. Down-regulation of MSH2 expression by an Hsp90 inhibitor enhances pemetrexed-induced cytotoxicity in human non-small-cell lung cancer cells.

    PubMed

    Tung, Chun-Liang; Chiu, Hsien-Chun; Jian, Yi-Jun; Jian, Yun-Ting; Chen, Chien-Yu; Syu, Jhan-Jhang; Wo, Ting-Yu; Huang, Yi-Jhen; Tseng, Sheng-Chieh; Lin, Yun-Wei

    2014-04-01

    Elevated heat shock protein 90 (Hsp90) expression has been linked to poor prognosis in patients with non-small cell lung cancer (NSCLC). The multitargeted antifolate pemetrexed has demonstrated certain clinical activities against NSCLC. However, the efficacy of the combination of pemtrexed and Hsp90 inhibitor to prolong the survival of patients with NSCLC still remains unclear. Human MutS homolog 2 (MSH2), a crucial element of the highly conserved DNA mismatch repair system, and defects or polymorphisms of MSH2 have been found in lung cancer. In this study, we evaluated the effects of pemetrexed on NSCLC cell lines (H520 and H1703) and found that treatment with this drug at 20-50 µM increased the MSH2 mRNA and protein levels in a MKK3/6-p38 MAPK signal activation-dependent manner. Furthermore, the knockdown of MSH2 expression by transfection with small interfering RNA of MSH2 or the blockage of p38 MAPK activation by SB202190 enhanced the cytotoxicity of pemetrexed. Combining the drug treatment with an Hsp90 inhibitor resulted in an enhanced pemetrexed-induced cytotoxic effect, accompanied with the reduction of MSH2 protein and mRNA levels. The expression of constitutively active MKK6 (MKK6E) or HA-p38 MAPK vectors significantly rescued the decreased p38 MAPK activity, and restored the MSH2 protein levels and cell survival in NSCLC cells co-treated with pemetrexed and Hsp90 inhibitor. In this study, we have demonstrated that down-regulation of the MKK3/6-p38 MAPK signal with the subsequent reduction of MSH2 enhanced the cytotoxic effect of pemetrexed in H520 and H1703 cells. The results suggest a potential future benefit of combining pemetrexed and the Hsp90 inhibitor to treat lung cancer. PMID:24530475

  4. Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer

    PubMed Central

    2014-01-01

    Background The efficacy and safety of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 in combination with pemetrexed and cisplatin was evaluated in patients with advanced non-squamous non–small-cell lung cancer (NSCLC). Methods Overall, 170 patients were randomly assigned to receive axitinib at a starting dose of 5-mg twice daily continuously plus pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 of up to six 21-day cycles (arm I); axitinib on days 2 through 19 of each cycle plus pemetrexed/cisplatin (arm II); or pemetrexed/cisplatin alone (arm III). The primary endpoint was progression-free survival (PFS). Results Median PFS was 8.0, 7.9, and 7.1 months in arms I, II, and III, respectively (hazard ratio: arms I vs. III, 0.89 [P = 0.36] and arms II vs. III, 1.02 [P = 0.54]). Median overall survival was 17.0 months (arm I), 14.7 months (arm II), and 15.9 months (arm III). Objective response rates (ORRs) for axitinib-containing arms were 45.5% (arm I) and 39.7% (arm II) compared with 26.3% for pemetrexed/cisplatin alone (arm III). Gastrointestinal disorders and fatigue were frequently reported across all treatment arms. The most common all-causality grade ≥3 adverse events were hypertension in axitinib-containing arms (20% and 17%, arms I and II, respectively) and fatigue with pemetrexed/cisplatin alone (16%). Conclusion Axitinib in combination with pemetrexed/cisplatin was generally well tolerated. Axitinib combinations resulted in non-significant differences in PFS and numerically higher ORR compared with chemotherapy alone in advanced NSCLC. Trial registration ClinicalTrials.gov: NCT00768755 (October 7, 2008). PMID:24766732

  5. Pemetrexed Injection

    MedlinePlus

    ... another chemotherapy (anti-cancer) medication to treat malignant pleural mesothelioma (a type of cancer that affects the ... effects.tell your doctor if you have a pleural effusion (excess fluid between the linings around the ...

  6. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Betamethasone acetate and betamethasone disodium phosphate aqueous suspension. 522.161 Section 522.161 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS...

  7. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  8. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  9. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  10. 40 CFR 721.3820 - L-Glutamic acid, N-(1-oxododecyl)-, disodium salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-Glutamic acid, N-(1-oxododecyl... Specific Chemical Substances § 721.3820 L-Glutamic acid, N-(1-oxododecyl)-, disodium salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  11. 40 CFR 721.3820 - L-Glutamic acid, N-(1-oxododecyl)-, disodium salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false L-Glutamic acid, N-(1-oxododecyl... Specific Chemical Substances § 721.3820 L-Glutamic acid, N-(1-oxododecyl)-, disodium salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  12. A subchronic oral toxicity study on pyrroloquinoline quinone (PQQ) disodium salt in rats.

    PubMed

    Liang, Chunlai; Zhang, Xin; Wang, Wei; Song, Yan; Jia, Xudong

    2015-01-01

    A subchronic oral toxicity study on pyrroloquinoline quinone (PQQ) disodium salt was performed in rats. Sprague-Dawley rats were randomly divided into four groups (10 rats/sex/group) and administered with PQQ disodium salt at doses of 0 (control), 100, 200 and 400 mg/kg bw/day by gavage for 13 weeks. Daily clinical observations and weekly measurement of body weights and food consumption were conducted. Blood samples were obtained on day 46 and day 91 for measurement of hematology and serum biochemical parameters. Animals were euthanized for necropsy, selected organs were weighted and recorded. Histological examination was performed on all tissues from animals in the control and PQQ disodium salt treatment groups. No mortality or toxicologically significant changes in clinical signs, body weight, food consumption, necropsy findings or organ weights was observed. Differences between treated and control groups in some hematological and serum biochemical examinations and histopathological examination were not considered treatment-related. The no-observed-adverse-effect-level (NOAEL) of PQQ disodium salt in rats was considered to be 400 mg/kg bw/day for both sexes, the highest dose tested. PMID:25445509

  13. Gadoxetate Disodium enhanced spectral dual-energy CT for evaluation of cholangiocarcinoma: Preliminary data

    PubMed Central

    Thomas, John V.; Bolus, David N.; Jackson, Bradford E.; Berland, Lincoln L.; Yester, Michael; Morgan, Desiree E.

    2016-01-01

    Purpose Evaluate Gadoxetate Disodium enhanced dual-energy CT for visualization of perihilar cholangiocarcinoma by exploiting the hepatobiliary uptake of Gadoxetate Disodium and viewing images at the k-edge of gadolinium on the spectrum of simulated monoenergetic energies available with Dual Energy CT. Material and methods In this prospective, IRB-approved study in patients with suspected cholangiocarcinoma, subjects who underwent a clinically indicated Gadoxetate Disodium liver MRI were immediately scanned without further IV contrast administration using rapid kVp-switching dual energy CT (rsDECT). Initial Gadoxetate Disodium dose was the FDA approved clinical dose, 0.025 mmol/kg; after additional IRB/FDA approval, 10 subjects were scanned with 0.05 mmol/kg. Both 50 keV and 70 keV simulated monoenergetic images as well as gadolinium(-water) material density images were viewed qualitatively and measured quantitatively for gadolinium uptake in the hepatic parenchyma and any focal lesions identified. Results Of 18 subjects (mean age 55 years, 10M, 8F, weight 84 kg), eight were scanned with 0.025 mmol/kg (Group 1) and 10 with 0.05 mmol/kg Gadoxetate Disodium (Group 2). Five patients had cholangiocarcinoma (all in Group 1). On synthetic monoenergetic images using standard and double Gadoxetate Disodium dose, the liver parenchyma did not appear enhanced qualitatively. Comparison of mean hepatic parenchymal HU at 50 and 70 keV showed a measurable increase in attenuation at the lower viewing energy, which corresponded to the k-edge of gadolinium. No statistically significant difference was observed on quantitative gadolinium measurement of hepatic parenchyma for single versus double Gadoxetate Disodium dose using rsDECT gadolinium material density images. Of the five cholangiocarcinomas, the tumor to nontumoral hepatic tissue HU differences were 51.1 (32.2) (mean and std dev) and 49.0(26.5) at 50 and 70 keV, respectively. Conclusion In this small pilot population

  14. [Morphological studies of hydroxyapatite crystals exposed to disodium pamidronate].

    PubMed

    Hein, L E; Grassi, R L; Roldán, E J; Gregori, D; Varela, M E; Piccinni, E P

    1997-01-01

    "In vitro" effects of disodium pamidronate on hydroxyapatite crystals morphology, and some "in vivo" data from bone powder of tibia and vertebrae from treated young and mature rabbits are here reported. Hydroxyapatite, synthesized following Rigoli et al method, and bone powder from rabbits were studied with X-ray, infrared and raman emission techniques for crystallographic analysis. Adsorption studies were also performed with a balanced solution of hydroxyapatite exposed to different times, 48, 120 and 168 hours and concentrations 1 x 10(-5) M, 3 x 10(-5) M, 8 x 10(-5) M y 1 x 10(-4) M of pamidronate. Infrared and raman spectrometry were not conclusive due to technical bias, but X-ray difractograms showed pure hydroxyapatite crystals in an hexagonal system. At constant time, pamidronate concentrations were varied, showing after 48 hours of exposition, a slight growth in the 002 plane, an aleatoric behavior in 213 and a marked increase in 004. After 120 hours, 002 plane is steady with a net growth in 004 and 213. After 168 hours, the 3 mentioned planes grow in proportion to pamidronate concentrations, tending to enlarge the crystal shape. Plane 13 markedly grow with pamidronate 8 x 10(-5) M a 1 x 10(-4) M, which are biologically high concentrations. Potentiometric assessments, in the 1 x 10(-5) to 1 x 10(-4) M range of concentrations show that bisphosphonate was completely adsorbed to the crystals. Additional "in vivo" observations showed changes in bone powder crystals isolated from pamidronate treated young animals, involving a growing of planes 002 and 211, in samples from both epiphysis and diaphysis, regarding untreated samples. Changes were more evident at epiphysis. In mature rabbits, it was shown a decrease in basal plane 002 and growing at 210, 211 and 310 with a trend to enlarge the crystal shape in diaphysis and to shorten it in vertebrate spongiosa. The "in vivo" doses are equivalent to those used by Ferretti et al. in intact rats with pamidronate low

  15. Synergistic activity of combination therapy with PEGylated pemetrexed and gemcitabine for an effective cancer treatment.

    PubMed

    Vandana, Mallaredy; Sahoo, Sanjeeb K

    2015-08-01

    Combination therapy in cancer is now opted as a potential therapeutic strategy for cancer treatment. However, effective delivery of drugs in combination at the tumor site is marred by low bioavailability and systemic toxicity of individual drugs. Polymer therapeutics is indeed an upcoming approach for the combinational drug delivery in favor of better cancer management. Hence, the objective of our investigation was to develop a dual drug PEGylated system that carries two chemotherapeutic drugs simultaneously for effective treatment of cancer. In this regard, we have synthesized Pem-PEG-Gem, wherein pemetrexed (Pem) and gemcitabine (Gem) are conjugated to a heterobifunctional polyethylene glycol (PEG) polymer for the effective treatment of Non-Small Cell Lung Cancer (NSCLC). Our results demonstrate enhanced bioavailability of the individual drugs in Pem-PEG-Gem in comparison with the drugs in their native form. The developed Pem-PEG-Gem showed enhanced cell death with respect to their native counterparts when treated singly or in combination against NSCLC cells. This might be attributed to better cellular internalization through the process of macropinocytosis and synergistic cytotoxic action of Pem-PEG-Gem in NSCLC cells. Hence, we propose the above dual drug based polymer therapeutic approach suitable for better clinical application in the treatment of NSCLC. PMID:25968494

  16. Phase I Trial of Radiation With Concurrent and Consolidation Pemetrexed and Cisplatin in Patients With Unresectable Stage IIIA/B Non-Small-Cell Lung Cancer

    SciTech Connect

    Brade, Anthony; Bezjak, Andrea; MacRae, Robert; Laurie, Scott; Sun, Alex; Cho, John; Leighl, Natasha; Pearson, Shannon; Southwood, Bernadette; Wang, Lisa; McGill, Shauna; Iscoe, Neill; Shepherd, Frances A.

    2011-04-01

    Purpose: To evaluate the feasibility and safety of concurrent pemetrexed/cisplatin/thoracic radiotherapy followed by consolidation pemetrexed/cisplatin for unresectable Stage IIIA/B non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible patients with <5% weight loss and good performance status received two cycles of pemetrexed (300, 400, or 500 mg/m{sup 2} on Days 1 and 22 for Dose Levels 1, 2, and 3/4, respectively) and cisplatin (25 mg/m{sup 2} Days 1-3 for Dose Levels 1-3; 20 mg/m{sup 2} Days 1-5 for Dose Level 4) concurrent with thoracic radiation (61-66 Gy in 31-35 fractions). Consolidation consisted of two cycles of pemetrexed/cisplatin (500 mg/m{sup 2}, 75 mg/m{sup 2}) 21 days apart, after concurrent therapy. Results: Between January 2006 and October 2007, 16 patients entered the study. Median follow-up was 17.2 months. No dose-limiting toxicities were observed. Median radiation dose was 64 Gy (range, 45-66 Gy). Rates of significant Grade 3/4 hematologic toxicity were 38% and 7%, respectively. One patient experienced Grade 3 acute esophagitis, and 2 experienced late (Grade 3) esophageal stricture, successfully managed with dilation. One patient experienced Grade 3 pneumonitis. The overall response rate was 88%. One-year overall survival was 81%. Conclusions: Full systemic dose pemetrexed seems to be safe with full-dose cisplatin and thoracic radiation in Stage IIIA/B NSCLC. Pemetrexed is the first third-generation cytotoxic agent tolerable at full dose in this setting. A Phase II study evaluating Dose Level 4 is ongoing.

  17. Reduced folate and serum vitamin metabolites in patients with rectal carcinoma: an open-label feasibility study of pemetrexed with folic acid and vitamin B12 supplementation

    PubMed Central

    Odin, Elisabeth A.; Carlsson, Göran U.; Kurlberg, Göran K.; Björkqvist, Hillevi G.; Tångefjord, Maria T.; Gustavsson, Bengt G.

    2016-01-01

    The objectives of this single-center, open-label, phase II study were to evaluate (a) the feasibility and safety of neoadjuvant administration of pemetrexed with oral folic acid and vitamin B12 (FA/B12) in newly diagnosed patients with resectable rectal cancer and (b) intracellular and systemic vitamin metabolism. Patients were treated with three cycles of pemetrexed (500 mg/m2, every 3 weeks) and FA/B12 before surgery. The reduced folates tetrahydrofolate, 5-methyltetrahydrofolate, and 5,10-methylenetetrahydrofolate were evaluated from biopsies in tumor tissue and in adjacent mucosa. Serum levels of homocysteine, cystathionine, and methylmalonic acid were also measured. All 37 patients received three cycles of pemetrexed; 89.2% completed their planned dosage within a 9-week feasibility time frame. Neither dose reductions nor study drug-related serious adverse events were reported. Reduced folate levels were significantly higher in tumor tissue compared with adjacent mucosa at baseline. After FA/B12 administration, tissue levels of reduced folates increased significantly and remained high during treatment in both tumor and mucosa until surgery. Serum levels of cystathionine increased significantly compared with baseline after FA/B12 administration, but then decreased, fluctuating cyclically during pemetrexed therapy. Homocysteine and methylmalonic acid levels decreased significantly after FA/B12 administration, and remained below baseline levels during the study. These results indicate that administration of three neoadjuvant cycles of single-agent pemetrexed, every 3 weeks, with FA/B12 in patients with resectable rectal cancer is feasible and tolerable. Tissue and serum vitamin metabolism results demonstrate the influence of pemetrexed and FA/B12 on vitamin metabolism and warrant further study. PMID:26825869

  18. Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta-analysis

    PubMed Central

    Xiao, Huai-Qing; Tian, Rong-Hua; Zhang, Zhi-Hao; Du, Kai-Qi; Ni, Yi-Ming

    2016-01-01

    Purpose To assess the efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC) through a trial-level meta-analysis. Methods Trials published between 1990 and 2015 were identified by an electronic search of public databases (Medline, Embase, and Cochrane Library). All clinical studies were independently identified by two authors. Demographic data, treatment regimens, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were extracted and analyzed using comprehensive meta-analysis software (version 2.0). Results A total of 2,551 patients with advanced nonsquamous NSCLC from ten trials were included for analysis: 1,565 patients were treated with pemetrexed plus platinum doublet chemotherapy and 986 with platinum plus other first-line chemotherapy. Pooled ORR for pemetrexed plus platinum chemotherapy was 37.8% (95% confidence interval [CI]: 31.7%–44.3%), with median PFS and OS of 5.7 and 16.05 months, respectively. When compared to other platinum-based doublet chemotherapies, the use of pemetrexed plus platinum chemotherapy significantly improved OS (hazard ratio [HR] =0.86, 95% CI: 0.77–0.97, P=0.01) but not PFS (HR =0.90, 95% CI: 0.80–1.01, P=0.084) in advanced nonsquamous NSCLC patients. Conclusion Pemetrexed plus platinum doublet regimen is an efficacious treatment for advanced nonsquamous NSCLC patients. Our findings support the use of pemetrexed plus platinum doublet regimen as first-line treatment in advanced nonsquamous NSCLC patients because of its potential survival benefits. PMID:27042115

  19. Reduced folate and serum vitamin metabolites in patients with rectal carcinoma: an open-label feasibility study of pemetrexed with folic acid and vitamin B12 supplementation.

    PubMed

    Stoffregen, Clemens C; Odin, Elisabeth A; Carlsson, Göran U; Kurlberg, Göran K; Björkqvist, Hillevi G; Tångefjord, Maria T; Gustavsson, Bengt G

    2016-06-01

    The objectives of this single-center, open-label, phase II study were to evaluate (a) the feasibility and safety of neoadjuvant administration of pemetrexed with oral folic acid and vitamin B12 (FA/B12) in newly diagnosed patients with resectable rectal cancer and (b) intracellular and systemic vitamin metabolism. Patients were treated with three cycles of pemetrexed (500 mg/m, every 3 weeks) and FA/B12 before surgery. The reduced folates tetrahydrofolate, 5-methyltetrahydrofolate, and 5,10-methylenetetrahydrofolate were evaluated from biopsies in tumor tissue and in adjacent mucosa. Serum levels of homocysteine, cystathionine, and methylmalonic acid were also measured. All 37 patients received three cycles of pemetrexed; 89.2% completed their planned dosage within a 9-week feasibility time frame. Neither dose reductions nor study drug-related serious adverse events were reported. Reduced folate levels were significantly higher in tumor tissue compared with adjacent mucosa at baseline. After FA/B12 administration, tissue levels of reduced folates increased significantly and remained high during treatment in both tumor and mucosa until surgery. Serum levels of cystathionine increased significantly compared with baseline after FA/B12 administration, but then decreased, fluctuating cyclically during pemetrexed therapy. Homocysteine and methylmalonic acid levels decreased significantly after FA/B12 administration, and remained below baseline levels during the study. These results indicate that administration of three neoadjuvant cycles of single-agent pemetrexed, every 3 weeks, with FA/B12 in patients with resectable rectal cancer is feasible and tolerable. Tissue and serum vitamin metabolism results demonstrate the influence of pemetrexed and FA/B12 on vitamin metabolism and warrant further study. PMID:26825869

  20. Controlled trial of disodium cromoglycate in prevention of relapse of steroid-responsive nephrotic syndrome of childhood.

    PubMed Central

    Trompeter, R S; Thomson, P D; Barratt, T M; Soothill, J F

    1978-01-01

    A controlled trial of disodium cromoglycate treatment of steroid-responsive nephrotic syndrome failed to show a therapeutic effect on the tendency to relapse after withdrawal of corticosteroids. PMID:96741

  1. Pemetrexed/Carboplatin/Bevacizumab followed by Maintenance Pemetrexed/Bevacizumab in Hispanic Patients with Non-Squamous Non-Small Cell Lung Cancer: Outcomes according to Thymidylate Synthase Expression

    PubMed Central

    Carranza, Hernán; Vargas, Carlos; Otero, Jorge; Cuello, Mauricio; Corrales, Luis; Martín, Claudio; Ortiz, Carlos; Franco, Sandra; Rosell, Rafael

    2016-01-01

    Objective To evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance therapy with pemetrexed and bevacizumab (PB) in chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS) protein and mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Methods A cohort of 144 patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5.0 mg/ml/min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance PB was administered until disease progression or unacceptable toxicity. Results One hundred forty-four Colombian patients with a median follow-up of 13.8 months and a median number of 6 maintenance cycles (range, 1–32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median PFS and (OS) rates were 7.9 months (95% CI, 5.9–10.0 months) and 21.4 months (95% CI, 18.3 to 24.4 months), respectively. We documented grade 3/4 hematologic toxicities, including anemia (14%), neutropenia (8%), and thrombocytopenia (16%). The identified grade 3/4 non-hematologic toxicities were proteinuria (2%), venous thrombosis (4%), fatigue (11%), infection (6%), nephrotoxicity (2%), and sensory neuropathy (4%). No grade >3 hemorrhagic events or hypertension cases were reported. OS was significantly higher in patients with the lowest TS mRNA levels [median, 29.6 months (95% CI, 26.2–32.9)] compared with those in patients with higher levels [median, 9.3 months (95% CI, 6.6–12.0); p = 0.0001]. TS expression (mRNA levels or protein expression) did not influence the treatment response. Conclusion Overall, PCB followed by maintenance pemetrexed and bevacizumab was effective and tolerable in Hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and

  2. Triple combination of irradiation, chemotherapy (pemetrexed), and VEGFR inhibition (SU5416) in human endothelial and tumor cells

    SciTech Connect

    Bischof, Marc; Abdollahi, Amir; Gong Ping; Stoffregen, Clemens; Lipson, Kenneth E.; Debus, Juergen; Weber, Klaus J.; Huber, Peter E. . E-mail: p.huber@dkfz.de

    2004-11-15

    Purpose: This is the first preclinical report evaluating a trimodal therapy consisting of irradiation, chemotherapy, and antiangiogenesis in the context of a multimodal anticancer strategy. The combination of the folate antimetabolite pemetrexed, SU5416, a receptor tyrosine kinase inhibitor of VEGFR2, and irradiation was investigated in human endothelial cells and tumor cell lines. Methods and materials: Primary isolated human umbilical vein endothelial cells (HUVEC), human dermal microvascular endothelial cells (HDMEC), and human glioblastoma (U87) and prostate cancer cells (PC3) were exposed to pemetrexed (2 h) alone and in combination with SU5416 (2 h). When combined with irradiation up to 8 Gy, fixed concentrations of pemetrexed (1.06 {mu}M) and SU5416 (1.0 {mu}M) were used. Proliferation and clonogenic assays were conducted with endothelial and tumor cells. The migration/invasion ability of endothelial cells and the ability to produce tubular structures were tested in Matrigel and tube formation assays. Apoptosis was measured by sub-G1 DNA and caspase-3 flow cytometry. To investigate underlying cell signaling, immunocytochemistry was used to detect Akt survival signaling involvement. Results: Triple combination using only a low-toxicity drug exposure of pemetrexed and SU5416 results in greater response than each treatment alone or than each combination of two modalities in all tested endothelial and tumor cell models. Triple combination substantially inhibits proliferation, migration/invasion, tube formation, and clonogenic survival. Triple combination also induced the highest rate of apoptosis in HDMEC and HUVEC as indicated by sub-1 G1 and caspase-3 assessment. Interestingly, triple combination therapy also reduces proliferation and clonogenic survival significantly in U87 and PC3 tumor cell lines. SU5416 potently inhibited Akt phosphorylation which could be induced by radiation and radiochemotherapy in human endothelial cells. Conclusions: Our findings

  3. Drugs Approved for Malignant Mesothelioma

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Malignant Mesothelioma This page lists cancer ... in malignant mesothelioma that are not listed here. Drugs Approved for Malignant Mesothelioma Alimta (Pemetrexed Disodium) Pemetrexed ...

  4. Human disodium octaborate tetrahydrate exposure following carpet flea treatment is not associated with significant dermal absorption.

    PubMed

    Krieger, R I; Dinoff, T M; Peterson, J

    1996-01-01

    Disodium octaborate tetrahydrate is used for indoor flea control on carpets and furniture. Disodium octaborate tetrahydrate was applied to a 100% nylon carpet as a solution using a powered rug brush at a rate of approximately 200 micrograms/cm2 carpet. Two randomly chosen groups of volunteers (18 females, 4 males) wore either bathing suits which provided 75% or more skin exposure or whole-body, cotton dosimeters consisting of socks, union suits, and gloves. The volunteers performed a 20-minute set of Jazzercise routines. The availability of boron was demonstrated by covering portions of the carpet with a cotton dosimeter and rolling it with a weighted roller. Additionally, disodium octaborate tetrahydrate was transferred to the whole-body dosimeter. Volunteers also collected 24-hour urine specimens prior to and following the exercise period. The specimens were analyzed for total boron by inductively coupled plasma emission spectroscopy. No evidence of contact transfer and dermal absorption was obtained. The mean daily boron levels (mg/g creatinine) were 1.17, 1.33, and 1.31 for the group with exposed skin and 1.26, 1.12, and 1.26 for those who wore dosimeters which prevented contact. Daily urine boron levels were not significantly different when compared using a two sample t-test assuming equal variances (P > 0.05). Direct dermal contact with disodium octaborate tetrahydrate-treated carpet at a nominal rate of 200 micrograms/cm2 did not produce any adverse effects or change urinary boron clearance. PMID:8889949

  5. The pharmacokinetics of subcutaneously injected Bimosiamose disodium in healthy male volunteers.

    PubMed

    Meyer, Michael; Beyer, Diana; Vollhardt, Karin; Woischwill, Christiane; Jilma, Bernd; Wolff, Gerhard

    2007-12-01

    Bimosiamose is a novel synthetic pan-selectin antagonist developed for the treatment of acute and chronic inflammatory disorders. Therefore the pharmacokinetics of Bimosiamose disodium were studied in healthy male volunteers after single and multiple subcutaneous injections. A randomized, double-blind, placebo-controlled dose escalation trial was carried out. The subjects received subcutaneous injections of placebo or 100, 200 or 300 mg Bimosiamose disodium into the abdomen. Plasma and urine concentrations of Bimosiamose were determined. The maximum plasma concentration was 2.17+/-0.70 microg/ml and the AUC(0-infinity) 11.1+/-2.9 h microg/ml after the highest dose on day 1 (mean+/-SD). For the apparent clearance CL/f 28.7+/-7.3 l/h and the terminal half life t(1/2) 3.7+/-0.6 h were calculated. The mean residence time MRT(infinity) of 5.5 to 6.3 h for s.c. injection exceeded that after i.v. infusion due to an extended absorption time. For multiple dosing, constant pre-dose concentrations of about 20 ng/ml may be reached after two subsequent doses of 200 or 300 mg Bimosiamose disodium once daily. Almost 15% of the administered drug was excreted unchanged in urine. Moreover, Bimosiamose was well tolerated. PMID:17876866

  6. Liposomal pemetrexed: formulation, characterization and in vitro cytotoxicity studies for effective management of malignant pleural mesothelioma.

    PubMed

    Essam Eldin, Noha; Elnahas, Hanan Mohamed; Mahdy, Mahmoud Abd-Elghany; Ishida, Tatsuhiro

    2015-01-01

    Pemetrexed (PMX) is a newly developed multi-targeted anti-folate with promising clinical activity in many solid tumors including malignant pleural mesothelioma (MPM). However, PMX does not show sufficient anti-tumor activity in vivo when used alone either due to inefficient delivery of adequate concentrations to tumor tissue or dose-limiting side effects. In order to overcome these problems and to achieve potent anti-tumor activity, PMX was encapsulated into a liposomal delivery system. In the present study, various formulations of liposomal PMX were prepared. The effect of formulation parameters on the encapsulation efficiency of PMX within liposomes was evaluated. In addition, the influence of drug release rate on the in vitro cytotoxicity was investigated. Encapsulation of PMX within liposomes was remarkably increased by the incorporation of cholesterol within liposomal membranes and by increasing the total lipid concentration. Encapsulation efficiency was found to be unaffected by the type of phospholipid used or the inclusion of a cation lipid, DC-6-14. Interestingly, encapsulation of PMX within "fluid" liposomes was found to allow efficient release of PMX from liposomes resulting in a potent in vitro cytotoxicity against MPM MSTO-211H cell line. On the other hand, entrapment of PMX within "solid" liposomes substantially hindered PMX release from liposomes, and thus PMX failed to exert any in vitro cytotoxicity. These results suggest that encapsulation of PMX within "fluid" liposomes might represent a novel strategy to enhance the therapeutic efficacy of PMX while minimizing the side effect encountered by the non selective delivery of free PMX to various body tissues. PMID:25757929

  7. Pemetrexed for advanced non-small cell lung cancer patients with interstitial lung disease

    PubMed Central

    2014-01-01

    Background Non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) need to be approached carefully given the high incidence of pulmonary toxicity. Pemetrexed (PEM) is the key drug for the treatment of NSCLC. However, its safety, especially with respect to the exacerbation of ILD, and efficacy in NSCLC patients with ILD have yet to be established. Method We investigated the safety and efficacy of PEM monotherapy in NSCLC patients with or without idiopathic interstitial pneumonia (IIPs). The medical charts of these patients were retrospectively reviewed. Results Twenty-five patients diagnosed as having IIPs (IIPs group) and 88 patients without ILD (non-ILD group) were treated with PEM monotherapy at Juntendo University Hospital between 2009 and 2013. In the IIPs group, 12 patients were found to have usual interstitial pneumonitis (UIP) on chest computed tomography (CT) (UIP group) and the other 13 patients showed a non-UIP pattern on chest CT (non-UIP IIPs group). Three patients in the IIPs group (2 in the UIP group and 1 in the non-UIP IIPs group) and 1 in the non-ILD group developed pulmonary toxicity during treatment (3.5% overall, 12.0% in the IIPs group versus 1.1% in the non-ILD group). Moreover, all 3 patients in the IIPs group died of pulmonary toxicity. Overall survival tended to be longer in the non-ILD group than in the IIPs group (p = 0.08). Multivariate analyses demonstrated that IIPs was the only significant independent risk factor for PEM-related pulmonary toxicity. Conclusion We found that the incidence of PEM-related pulmonary toxicity was significantly higher amongst NSCLC patients with IIPs than among those without IIPs. Particular care must be taken when administering PEM to treat NSCLC patients with IIPs. PMID:25012241

  8. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-06-01

    (+)-Dapoxetine hydrochloride; Abatacept, Adalimumab, Agalsidase beta, Alemtuzumab, Alglucosidase alfa, Aliskiren fumarate, Ambrisentan, Amlodipine, Aripiprazole, Atrasentan, Azacitidine, Azelnidipine; Belotecan hydrochloride, Bevacizumab, Bilastine, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, CG-100649, Cinacalcet hydrochloride, Clindamycin phosphate/ benzoyl peroxide; Dasatinib, Denosumab, Duloxetine hydrochloride, Dutasteride, Dutasteride/tamsulosin; Ecogramostim, Eculizumab, Eltrombopag olamine, EndoTAG-1, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe; FAHF-2, Fondaparinux sodium; Gefitinib, Golimumab; HEV-239, HSV-TK; Imatinib mesylate, Indium 111 ((111)In) ibritumomab tiuxetan, Influenza vaccine(surface antigen, inactivated, prepared in cell culture), Insulin glargine; Kisspeptin-54; Lidocaine/prilocaine, Lomitapide; Maraviroc, Mirodenafil hydrochloride, MK-8141, MVA-Ag85A; Nilotinib hydrochloride monohydrate; Olmesartan medoxomil; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pitavastatin calcium, Prasugrel; Recombinant human relaxin H2, RHAMM R3 peptide, Rivaroxaban, Rosuvastatin calcium, RRz2; Sagopilone, Salinosporamide A, SB-509, Serlopitant, Sirolimus-eluting stent, Sorafenib, Sunitinib malate; Tadalafil, Temsirolimus, Teriparatide, TG-4010, Tositumomab/iodine (I131) tositumomab; Velusetrag Hydrochloride; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:19649342

  9. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-06-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-chlorotoxin; Ad5CMV-p53, adalimumab, albumin interferon alfa, alemtuzumab, aliskiren fumarate, aminolevulinic acid methyl ester, anakinra, AR-C126532, atomoxetine hydrochloride; Bevacizumab, bosentan, botulinum toxin type B, brimonidine tartrate/timolol maleate; Calcipotriol/betamethasone dipropionate, cangrelor tetrasodium, cetuximab, ciclesonide, cinacalcet hydrochloride, collagen-PVP, Cypher; Darbepoetin alfa, darusentan, dasatinib, denosumab, desloratadine, dexosome vaccine (lung cancer), dexrazoxane, dextromethorphan/quinidine sulfate, duloxetine hydrochloride; ED-71, eel calcitonin, efalizumab, entecavir, etoricoxib; Falciparum merozoite protein-1/AS02A, fenretinide, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gefitinib, ghrelin (human); hLM609; Icatibant acetate, imatinib mesylate, ipsapirone, irofulven; LBH-589, LE-AON, levocetirizine, LY-450139; Malaria vaccine, mapatumumab, motexafin gadolinium, muraglitazar, mycophenolic acid sodium salt; nab-paclitaxel, nelarabine; O6-Benzylguanine, olmesartan medoxomil, orbofiban acetate; Panitumumab, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, peptide YY3-36, pleconaril, prasterone, pregabalin; Ranolazine, rebimastat, recombinant malaria vaccine, rosuvastatin calcium; SQN-400; Taxus, tegaserod maleate, tenofovir disoproxil fumarate, teriparatide, troxacitabine; Valganciclovir hydrochloride, Val-Tyr sardine peptidase, VNP-40101M, vorinostat. PMID:16845450

  10. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-09-01

    Aclidinium bromide, AE-37, Alemtuzumab, AMA1-C1/ISA 720, Amlodipine besylate/atorvastatin calcium, Arachidonic acid, Arbaclofen placarbil, Aripiprazole, ARQ-621, Azelnidipine, Azilsartan medoxomil potassium; Bevacizumab, Biphasic insulin aspart, Bortezomib; Choriogonadotropin alfa, CTS-1027; Dapagliflozin, Dasatinib, Deforolimus, Degarelix acetate, Denufosol tetrasodium, Desvenlafaxine succinate, Dronedarone hydrochloride, Duloxetine hydrochloride, Dutasteride; Enfuvirtide, Entecavir, Etaracizumab, Everolimus, Exenatide, Ezetimibe; Ferric carboxymaltose, Fludarabine, Foretinib; Gefitinib, GFT-505, GSK-256066; HPV-6/11/16/18, HuM195/rGel, HyperAcute-Lung cancer vaccine; I5NP, Imatinib mesylate, Imexon, Insulin detemir, Insulin glargine, Ivabradine hydrochloride; L2G7, Lacosamide, Lapatinib ditosylate, Lenalidomide, Lidocaine/prilocaine, Liposomal vincristine, Liraglutide, Lixivaptan; Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine, Methoxy polyethylene glycol-epoetin-β, Mirabegron, Morphine/oxycodone, MR Vaccine, MSC-1936369B, Mycophenolic acid sodium salt; Narlaprevir, N-Desmethylclozapine; Ocriplasmin, Olaparib, Olmesartan medoxomil, Olmesartan medoxomil/azelnidipine, ONO-5334, ONO-8539; Palifermin, Panitumumab, Pardoprunox hydrochloride, PCV7, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pexelizumab, PF-337210, Pitavastatin calcium; Raltegravir potassium, Recombinant interleukin-7, Regadenoson, Reniale, Roflumilast, Rosuvastatin calcium; Safinamide mesilate, SB-1518, SCH-527123, Selumetinib, Sipuleucel-T, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talaporfin sodium, Tanespimycin, Technosphere/Insulin, Telaprevir, Telatinib, Telcagepant, Telmisartan/hydrochlorothiazide, Teriparatide, Testosterone transdermal gel, TH-302, Tiotropium bromide, Tocilizumab, Trabedersen, Tremelimumab; Valsartan/amlodipine besylate, Vernakalant hydrochloride, Visilizumab, Voreloxin, Vorinostat. PMID

  11. Phase 2 Study of Pemetrexed and Itraconazole as Second-Line Therapy for Metastatic Non-Squamous Non-Small Cell Lung Cancer

    PubMed Central

    Rudin, Charles M.; Brahmer, Julie R.; Juergens, Rosalyn A.; Hann, Christine L.; Ettinger, David S.; Sebree, Rosa; Smith, Ruth; Aftab, Blake T.; Huang, Peng; Liu, Jun O.

    2013-01-01

    Purpose Preclinical studies suggested that the oral anti-fungal agent itraconazole specifically inhibits proliferation, migration, and tube formation of endothelial cells. Itraconazole has potent anti-angiogenic activity and enhances the efficacy of cytotoxic chemotherapy in multiple primary xenograft lung cancer models. Based on these data, we performed an exploratory clinical study assessing the efficacy of itraconazole with cytotoxic chemotherapy in the treatment of patients with advanced lung cancer. Patients/Methods The study enrolled patients with progressive non-squamous non-small cell lung cancer after one prior cytotoxic therapy for metastatic disease, randomized 2:1 to pemetrexed 500 mg/m2 IV day 1 with or without itraconazole 200 mg oral daily on a 21-day cycle. Outcome measures included percent progression-free at 3 months, progression-free survival, overall survival, and observed toxicity. Results A total of 23 patients were enrolled; the study was stopped early due to increasing use of pemetrexed in the first line setting. Sixty-seven percent of patients were progression-free at 3 months on itraconazole plus pemetrexed vs. 29% on the control arm of pemetrexed alone (p=0.11). Median progression-free survivals were 5.5 months (itraconazole) vs. 2.8 months (control) (hazard ratio (HR)=0.399, p=0.089). Overall survival was longer in patients receiving itraconazole (median 32 months) vs. control (8 months) (HR=0.194, p=0.012). There were no evident differences in toxicity between the study arms. Conclusion Itraconazole is well tolerated in combination with pemetrexed. Consistent with our preclinical data, daily itraconazole administration is associated with trends suggestive of improved disease control in patients receiving chemotherapy for advanced lung cancer. PMID:23546045

  12. [Disodium cromoglycate--mast cell degranulation blocker in the process of tissue remodelation].

    PubMed

    Maxová, H; Vasilková, M; Tkaczyk, J; Vízek, M

    2010-01-01

    Disodium cromoglycate (DSCG) is a compound commonly used in the treatment of allergic diseases. The effect of DSCG is due to its ability to stabilize the mast cell membrane and to prevent release of histamine and inflammatory mediators. Mast cells are also an abundant source of tissue metalloproteinases, serine proteases and growth factors, which play an important role in the processes of the tissue remodeling. In this view the DSCG is a substance which allows us to study the mechanisms of the pulmonary vascular bed remodeling in the experimental animals exposed to chronic hypoxia and in a phase of the recovery from hypoxia. PMID:21254664

  13. Chelation in metal intoxication. XVIII. Combined effects of thiamine and calcium disodium versenate on lead toxicity

    SciTech Connect

    Flora, S.J.S.; Singh, S.; Tandon, S.K.

    1986-01-06

    Calcium disodium ethylenediaminetetra-acetate (Ca-Na/sub 2/EDTA; Versenate) was more effective than thiamine (vitamin B/sub 1/) in enhancing the urinary excretion of lead, reducing tissue lead and restoring lead induced biochemical alterations in rats. However, the combination of CaNa/sub 2/EDTA and vitamin B/sub 1/ enhanced the beneficial effect of CaNa/sub 2/EDTA in lead intoxication and was particularly effective in reducing the brain concentration of lead. 18 references, 1 figure, 2 tables.

  14. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX-Lung 3.

    PubMed

    Kato, Terufumi; Yoshioka, Hiroshige; Okamoto, Isamu; Yokoyama, Akira; Hida, Toyoaki; Seto, Takashi; Kiura, Katsuyuki; Massey, Dan; Seki, Yoko; Yamamoto, Nobuyuki

    2015-09-01

    In LUX-Lung 3, afatinib significantly improved progression-free survival (PFS) versus cisplatin/pemetrexed in EGFR mutation-positive lung adenocarcinoma patients and overall survival (OS) in Del19 patients. Preplanned analyses in Japanese patients from LUX-Lung 3 were performed. Patients were randomized 2:1 to afatinib or cisplatin/pemetrexed, stratified by mutation type (Del19/L858R/Other). Primary endpoint was PFS (independent review). Secondary endpoints included OS, objective response, and safety. Median PFS (data cut-off: February 2012) for afatinib versus cisplatin/pemetrexed was 13.8 vs 6.9 months (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20-0.70; P = 0.0014) in all Japanese patients (N = 83), with more pronounced improvements in those with common mutations (Del19/L858R; HR, 0.28; 95% CI, 0.15-0.52; P < 0.0001) and Del19 mutations (HR, 0.16; 95% CI, 0.06-0.39; P < 0.0001). PFS was also improved in L858R patients (HR, 0.50; 95% CI, 0.20-1.25; P = 0.1309). Median OS (data cut-off: November 2013) with afatinib versus cisplatin/pemetrexed was 46.9 vs 35.8 months (HR, 0.75; 95% CI, 0.40-1.43; P = 0.3791) in all Japanese patients, with greater benefit in patients with common mutations (HR, 0.57; 95% CI, 0.29-1.12; P = 0.0966) and Del19 mutations (HR, 0.34; 95% CI, 0.13-0.87; P = 0.0181); OS was not significantly different in L858R patients (HR, 1.13; 95% CI, 0.40-3.21; P = 0.8212). Following study treatment discontinuation, most patients (93.5%) received subsequent anticancer therapy. The most common treatment-related adverse events were diarrhea, rash/acne, nail effects and stomatitis with afatinib and nausea, decreased appetite, neutropenia, and leukopenia with cisplatin/pemetrexed. Afatinib significantly improved PFS versus cisplatin/pemetrexed in Japanese EGFR mutation-positive lung adenocarcinoma patients and OS in Del19 but not L858R patients (www.clinicaltrials.gov; NCT00949650). PMID:26094656

  15. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX-Lung 3

    PubMed Central

    Kato, Terufumi; Yoshioka, Hiroshige; Okamoto, Isamu; Yokoyama, Akira; Hida, Toyoaki; Seto, Takashi; Kiura, Katsuyuki; Massey, Dan; Seki, Yoko; Yamamoto, Nobuyuki

    2015-01-01

    In LUX-Lung 3, afatinib significantly improved progression-free survival (PFS) versus cisplatin/pemetrexed in EGFR mutation-positive lung adenocarcinoma patients and overall survival (OS) in Del19 patients. Preplanned analyses in Japanese patients from LUX-Lung 3 were performed. Patients were randomized 2:1 to afatinib or cisplatin/pemetrexed, stratified by mutation type (Del19/L858R/Other). Primary endpoint was PFS (independent review). Secondary endpoints included OS, objective response, and safety. Median PFS (data cut-off: February 2012) for afatinib versus cisplatin/pemetrexed was 13.8 vs 6.9 months (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.70; P = 0.0014) in all Japanese patients (N = 83), with more pronounced improvements in those with common mutations (Del19/L858R; HR, 0.28; 95% CI, 0.15–0.52; P < 0.0001) and Del19 mutations (HR, 0.16; 95% CI, 0.06–0.39; P < 0.0001). PFS was also improved in L858R patients (HR, 0.50; 95% CI, 0.20–1.25; P = 0.1309). Median OS (data cut-off: November 2013) with afatinib versus cisplatin/pemetrexed was 46.9 vs 35.8 months (HR, 0.75; 95% CI, 0.40–1.43; P = 0.3791) in all Japanese patients, with greater benefit in patients with common mutations (HR, 0.57; 95% CI, 0.29–1.12; P = 0.0966) and Del19 mutations (HR, 0.34; 95% CI, 0.13–0.87; P = 0.0181); OS was not significantly different in L858R patients (HR, 1.13; 95% CI, 0.40–3.21; P = 0.8212). Following study treatment discontinuation, most patients (93.5%) received subsequent anticancer therapy. The most common treatment-related adverse events were diarrhea, rash/acne, nail effects and stomatitis with afatinib and nausea, decreased appetite, neutropenia, and leukopenia with cisplatin/pemetrexed. Afatinib significantly improved PFS versus cisplatin/pemetrexed in Japanese EGFR mutation-positive lung adenocarcinoma patients and OS in Del19 but not L858R patients (www.clinicaltrials.gov; NCT00949650). PMID:26094656

  16. Synergistic effects of pemetrexed and amrubicin in non-small cell lung cancer cell lines: Potential for combination therapy.

    PubMed

    Hatakeyama, Yukihisa; Kobayashi, Kazuyuki; Nagano, Tatsuya; Tamura, Daisuke; Yamamoto, Masatsugu; Tachihara, Motoko; Kotani, Yoshikazu; Nishimura, Yoshihiro

    2014-02-01

    The purpose is to examine the synergistic effect of pemetrexed (PEM) and amrubicin (AMR) on the proliferation of lung cancer cell lines. In vitro, dose-dependent synergistic effects of concurrent PEM and AMRol, which is an active metabolite of AMR were observed in A549 and H460 cells. In real-time RT-qPCR analysis and western blotting, expression of the target enzymes of PEM were suppressed in cells treated with amrubicinol alone. In vivo, AMR/PEM treatment also showed synergistic antitumor activity both in A549-bearing and H520-bearing mice. PEM and AMR work synergistically to inhibit the proliferation of several different lung cancer cell lines. PMID:24139969

  17. A Prospective Study of Shortened Vitamin Supplementation Prior to Cisplatin–Pemetrexed Therapy for Non-Small Cell Lung Cancer

    PubMed Central

    Hosomi, Yukio; Sunami, Kuniko; Nakahara, Yoshiro; Okuma, Yusuke; Yomota, Makiko; Shimokawa, Tsuneo; Nagamata, Makoto; Iguchi, Mari; Okamoto, Hiroaki; Okamura, Tatsuru; Shibuya, Masahiko

    2014-01-01

    Background. Prior supplementation with folic acid and vitamin B12 is required to reduce pemetrexed therapy toxicity; the recommended lead-in time is at least 7 days. On the basis of previous pharmacokinetic and clinical studies, we hypothesized that the lead-in time could be shortened to 24 hours, enabling earlier commencement of standard chemotherapy; thus, we planned the first prospective trial of this regimen. Methods. Patients with advanced nonsquamous non-small cell lung cancer who had not previously received cytotoxic chemotherapy were enrolled. After measurement of homocysteine concentrations, the patients received 1,000 μg of vitamin B12 by intramuscular injection and began taking 350–500 μg of oral folic acid daily. Starting 24–48 hours after the vitamin B12 injection, the patients received intravenous 500 mg/m2 pemetrexed and 75 mg/m2 cisplatin for 4 cycles at 3 weekly intervals. The primary endpoint was the proportion of patients who developed neutropenia grade ≥3. Results. Thirty patients received chemotherapy starting within 48 hours of the vitamin B12 injection. No treatment-related deaths or grade 4 toxicity occurred. Neutropenia grade ≥3, other laboratory toxicities grade ≥3, and nonlaboratory toxicities grade ≥3 occurred in 6.7%, 13%, and 13% of patients, respectively. The baseline homocysteine concentrations were not higher in patients with grade ≥3 toxicities than in the remainder of the cohort (mean values, 8.6 and 10.7 μmol/L, respectively). The response rate to chemotherapy was 43%. Conclusion. The shortened vitamin supplementation was well tolerated and retained antitumor efficacy. Analysis of baseline homocysteine concentrations confirmed the efficacy of short-term vitamin supplementation. PMID:25260366

  18. Effect of amino acids on the dispersion of disodium cromoglycate powders.

    PubMed

    Chew, Nora Y K; Shekunov, Boris Y; Tong, Henry H Y; Chow, Albert H L; Savage, Charles; Wu, James; Chan, Hak-Kim

    2005-10-01

    Modified disodium cromoglycate powders were prepared by co-spray drying with different concentrations of leucine, phenylalanine, tryptophan, methionine, asparagine, and arginine. Amorphous spherical particles of the same size and density where obtained which, however, exhibited different surface properties as measured by the inverse gas chromatography (IGC) and X-ray photoelectron spectroscopy (XPS) techniques. The surface energy parameters, such as the dispersive component of surface free energy of the sample, gammaSD, and the total solubility parameter, delta, were significantly lower in the presence of nonpolar chain amino acids, particularly with leucine and phenylalanine, than pure DSCG. However no quantitative relationship between these parameters, the additive concentrations, and the fine particle fractions, FPF, determined for different inhalers and air flow rates, was observed. The FPF significantly increased with addition of leucine and this effect was attributed to reduced intermolecular interactions between leucine and disodium cromoglycate molecules, as indicated by the difference in corresponding Hansen solubility parameters. Decrease of interparticle interactions for leucine-containing powders also led to a lesser dependence of FPF on the flow rate and inhaler type. PMID:16136546

  19. Development and cross-validation of prognostic models to assess the treatment effect of cisplatin/pemetrexed chemotherapy in lung adenocarcinoma patients.

    PubMed

    Mou, Wenjun; Liu, Zhaoqi; Luo, Yuan; Zou, Meng; Ren, Chao; Zhang, Chunyan; Wen, Xinyu; Wang, Yong; Tian, Yaping

    2014-09-01

    Better understanding of the treatment effect of cisplatin/pemetrexed chemotherapy on lung adenocarcinoma patients is needed to facilitate chemotherapy planning and patient care. In this retrospective study, we will develop prognostic models by the cross-validation method using clinical and serum factors to predict outcomes of cisplatin/pemetrexed chemotherapy in lung adenocarcinoma patients. Lung adenocarcinoma patients admitted between 2008 and 2013 were enrolled. 29 serum parameters of laboratory tests and 14 clinical factors were analyzed to develop the prognostic models. First, the stepwise selection and five-fold cross-validation were performed to identify candidate prognostic factors. Then a classification of all patients based on the number of metastatic sites resulted in four distinct subsets. In each subset, a prognostic model was fitted with the most accurate prognostic factors from the candidate prognostic factors. Categorical survival prediction was estimated using a log-rank test and visualized with Kaplan-Meier method. 227 lung adenocarcinoma patients were enrolled. Twenty candidate prognostic factors evaluated using the five-fold cross-validation method were total protein, total bilirubin, direct bilirubin, creatine kinase, age, smoking index, neuron-specific enolase, bone metastasis, total triglyceride, albumin, gender, uric acid, CYFRA21-1, lymph node metastasis, liver metastasis, lactate dehydrogenase, CA153, peritoneal metastasis, CA125, and CA199. From these 20 candidate prognostic factors, the multivariate Cox proportional hazard model with the highest prognostic accuracy in each subset was identified by the stepwise forward selection method, which generated significant prognostic stratifications in Kaplan-Meier survival analyses (all log-rank p < 0.01). Generally, the prognostic models using five-fold cross-validation achieve a good prediction performance. The prognostic models can be administered safely to lung adenocarcinoma patients treated

  20. Nephrogenic Systemic Fibrosis Risk After Liver Magnetic Resonance Imaging With Gadoxetate Disodium in Patients With Moderate to Severe Renal Impairment

    PubMed Central

    Lauenstein, Thomas; Ramirez-Garrido, Francisco; Kim, Young Hoon; Rha, Sung Eun; Ricke, Jens; Phongkitkarun, Sith; Boettcher, Joachim; Gupta, Rajan T.; Korpraphong, Pornpim; Tanomkiat, Wiwatana; Furtner, Julia; Liu, Peter S.; Henry, Maren; Endrikat, Jan

    2015-01-01

    Objective The objective of this study was to assess the risk of gadoxetate disodium in liver imaging for the development of nephrogenic systemic fibrosis (NSF) in patients with moderate to severe renal impairment. Materials and Methods We performed a prospective, multicenter, nonrandomized, open-label phase 4 study in 35 centers from May 2009 to July 2013. The study population consisted of patients with moderate to severe renal impairment scheduled for liver imaging with gadoxetate disodium. All patients received a single intravenous bolus injection of 0.025-mmol/kg body weight of liver-specific gadoxetate disodium. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. Results A total of 357 patients were included, with 85 patients with severe and 193 patients with moderate renal impairment, which were the clinically most relevant groups. The mean time period from diagnosis of renal disease to liver magnetic resonance imaging (MRI) was 1.53 and 5.46 years in the moderate and severe renal impairment cohort, respectively. Overall, 101 patients (28%) underwent additional contrast-enhanced MRI with other gadolinium-based MRI contrast agents within 12 months before the start of the study or in the follow-up. No patient developed symptoms conclusive of NSF within the 2-year follow-up. Conclusions Gadoxetate disodium in patients with moderate to severe renal impairment did not raise any clinically significant safety concern. No NSF cases were observed. PMID:25756684

  1. Phases and structures of sunset yellow and disodium cromoglycate mixtures in water

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Akihiro; Smith, Gregory P.; Yi, Youngwoo; Xu, Charles; Biffi, Silvia; Serra, Francesca; Bellini, Tommaso; Zhu, Chenhui; Clark, Noel A.

    2016-01-01

    We study phases and structures of mixtures of two representative chromonic liquid crystal materials, sunset yellow FCF (SSY) and disodium cromoglycate (DSCG), in water. A variety of combinations of isotropic, nematic (N ), and columnar (also called M ) phases are observed depending on their concentrations, and a phase diagram is made. We find a tendency for DSCG-rich regions to show higher-order phases while SSY-rich regions show lower-order ones. We observe uniform mesophases only when one of the materials is sparse in the N phases. Their miscibility in M phases is so low that essentially complete phase separation occurs. X-ray scattering and spectroscopy studies confirm that SSY and DSCG molecules do not mix when they form chromonic aggregates and neither do their aggregates when they form M phases.

  2. The inhibitory effect of disodium cromoglycate on the growth of Chlamydophila (Chlamydia) pneumoniae in vitro.

    PubMed

    Yamazaki, Tsutomu; Yamaguchi, Tetsuya; Sasaki, Nozomu; Inoue, Miyuki; Sato, Kozue; Kishimoto, Toshio

    2006-04-01

    Chlamydophila (Chlamydia) pneumoniae is associated with asthma and several other respiratory illnesses. Disodium cromoglycate (DSCG) is known to inhibit both immediate and late asthmatic responses. In this study, the inhibitory effect of DSCG on the growth of C. pneumoniae was examined by minimum inhibitory concentration (MIC) and pre-inoculation minimal cidal concentration (MCC) assays using HL cells and C. pneumoniae AR-39. DSCG below the clinically relevant concentration inhibited the growth of C. pneumoniae in a dose-dependent manner in both the MCC and MIC assays. The inhibitory effect was also time-dependent in the MCC assay at 20 mg/ml of DSCG. These results warrant further clinical study on the connection between C. pneumoniae infections and use of DSCG. PMID:16595921

  3. Effect of disodium cromoglycate on mast cell-mediated immediate-type allergic reactions.

    PubMed

    Shin, Hye-Young; Kim, Jung-Sook; An, Nyeon-Hyoung; Park, Rae-Kil; Kim, Hyung-Min

    2004-04-23

    We investigated the effect of disodium cromoglycate (DSCG) on mast cell-mediated immediate-type hypersensitivity. DSCG inhibited systemic allergic reaction induced by compound 48/80 dose-dependently. Passive cutaneous anaphylaxis was inhibited by 71.6% by oral administration of DSCG (1 g/kg). When DSCG was pretreated at concentration rang from 0.01-1000 g/kg, the serum histamine levels were reduced in a dose dependent manner. DSCG also significantly inhibited histamine release from rat peritoneal mast cell (RPMC) by compound 48/80. We confirmed that DSCG inhibited compound 48/80-induced degranulation of RPMC by alcian blue/nuclear fast red staining. In addition, DSCG showed a significant inhibitory effect on anti-dinitrophenyl IgE-mediated tumor necrosis factor-alpha production. These results indicate that DSCG inhibits mast cell-mediated immediate-type allergic reaction. PMID:15050425

  4. Disodium cromoglycate prevents ileum hyperreactivity to histamine in Toxocara canis-infected guinea pigs.

    PubMed

    Sá-Nunes, A; Corrado, A P; Baruffi, M D; Faccioli, L H

    2003-11-01

    The aim of this study was to investigate whether Toxocara canis infection in guinea pigs provokes changes in ileum responsiveness to histamine. Ileum segments from control and T. canis-infected groups were placed at isometric conditions and submitted to various doses of histamine. No changes were observed between controls and T. canis-infected groups at days 3, 6 and 12 after infection. However, at days 18 and 24 after infection, there was a significant increase in ileum responsiveness to histamine in T. canis-infected group. Pre-incubation of ileum segments with 1mgml(-1) disodium cromoglycate (DSCG) prevented the increased responsiveness to histamine in T. canis-infected guinea pigs and did not affect ileum contractility in non-infected animals. These results indicate that T. canis-infected guinea pigs develop increased intestinal responsiveness to histamine and that DSCG prevents alterations in smooth-muscle contractility. PMID:12967589

  5. Phases and structures of sunset yellow and disodium cromoglycate mixtures in water.

    PubMed

    Yamaguchi, Akihiro; Smith, Gregory P; Yi, Youngwoo; Xu, Charles; Biffi, Silvia; Serra, Francesca; Bellini, Tommaso; Zhu, Chenhui; Clark, Noel A

    2016-01-01

    We study phases and structures of mixtures of two representative chromonic liquid crystal materials, sunset yellow FCF (SSY) and disodium cromoglycate (DSCG), in water. A variety of combinations of isotropic, nematic (N), and columnar (also called M) phases are observed depending on their concentrations, and a phase diagram is made. We find a tendency for DSCG-rich regions to show higher-order phases while SSY-rich regions show lower-order ones. We observe uniform mesophases only when one of the materials is sparse in the N phases. Their miscibility in M phases is so low that essentially complete phase separation occurs. X-ray scattering and spectroscopy studies confirm that SSY and DSCG molecules do not mix when they form chromonic aggregates and neither do their aggregates when they form M phases. PMID:26871132

  6. Comparative in vitro studies on disodium EDTA effect with and without Proteus mirabilis on the crystallization of carbonate apatite and struvite

    NASA Astrophysics Data System (ADS)

    Prywer, Jolanta; Olszynski, Marcin; Torzewska, Agnieszka; Mielniczek-Brzóska, Ewa

    2014-06-01

    Effect of disodium EDTA (salt of ethylenediamine tetraacetic acid) on the crystallization of struvite and carbonate apatite was studied. To evaluate such an effect we performed an experiment of struvite and carbonate apatite growth from artificial urine. The crystallization process was induced by Proteus mirabilis to mimic the real urinary tract infection, which usually leads to urinary stone formation. The results demonstrate that disodium EDTA exhibits the effect against P. mirabilis retarding the activity of urease - an enzyme produced by these microorganisms. The spectrophotometric results demonstrate that, with and without P. mirabilis, the addition of disodium EDTA increases the induction time and decreases the growth efficiency compared to the baseline (without disodium EDTA). These results are discussed from the standpoint of speciation of complexes formed in the solution of artificial urine in the presence of disodium EDTA. The size of struvite crystals was found to decrease in the presence of disodium EDTA. However, struvite crystals are larger in the presence of bacteria while the crystal morphology and habit remain unchanged.

  7. Photochemical intracomplex reaction between [beta]-cyclodextrin and anthraquinone-2,6-disulfonic acid disodium salt in water solution

    NASA Astrophysics Data System (ADS)

    Petrova, S. S.; Kruppa, A. I.; Leshina, T. V.

    2005-05-01

    1D and 2D 1H NMR studies of anthraquinone-2,6-disulfonic acid disodium salt in the β-cyclodextrin solution have identified the inclusion complex formation. The association constant of AQDS-β-CD inclusion complex was determined as 800 ± 100 M -1. The selective intra-complex photo-oxidation of β-cyclodextrin at C6 position was detected by CIDNP method.

  8. Trial on Refinement of Early stage non-small cell lung cancer. Adjuvant chemotherapy with pemetrexed and cisplatin versus vinorelbine and cisplatin: The TREAT protocol

    PubMed Central

    Kreuter, Michael; Vansteenkiste, Johan; Griesinger, Frank; Hoffmann, Hans; Dienemann, Hendrik; De Leyn, Paul; Thomas, Michael

    2007-01-01

    Background Adjuvant chemotherapy has been proven to be beneficial for patients with early stage non-small cell lung cancer. However, toxicity and insufficient dose delivery have been critical issues with the chemotherapy used. Doublet regimens with pemetrexed, a multi-target folate inhibitor, and platin show clear activity in non-small cell lung cancer and are well tolerated with low toxicity rates and excellent delivery. Methods/Design In this prospective, multi-center, open label randomized phase II study, patients with pathologically confirmed non-small cell lung cancer, stage IB, IIA, IIB, T3N1 will be randomized after complete tumor resection either to 4 cycles of the standard adjuvant vinorelbine and cisplatin regimen from the published phase III data, or to 4 cycles of pemetrexed 500 mg/m2 d1 and cisplatin 75 mg/m2 d1, q 3 weeks. Primary objective is to compare the clinical feasibility of these cisplatin doublets defined as non-occurrence of grade 4 neutropenia and/or thrombocytopenia > 7 days or bleeding, grade 3/4 febrile neutropenia and/or infection, grade 3/4 non-hematological toxicity, non-acceptance leading to premature withdrawal and no cancer or therapy related death. Secondary parameters are efficacy (time to relapse, overall survival) and drug delivery. Parameters of safety are hematologic and non-hematologic toxicity of both arms. Discussion The TREAT trial was designed to evaluate the clinical feasibility, i.e. rate of patients without dose limiting toxicities or premature treatment withdrawal or death of the combination of cisplatin and pemetrexed as well as the published phase III regimen of cisplatin and vinorelbine. Hypothesis of the study is that reduced toxicities might improve the feasibility of drug delivery, compliance and the convenience of treatment for the patient and perhaps survival. Trial Registration Clinicaltrials.gov NCT00349089 PMID:17488518

  9. Phase II clinical trial of amatuximab, a chimeric anti-mesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma

    PubMed Central

    Hassan, Raffit; Kindler, Hedy L.; Jahan, Thierry; Bazhenova, Lyudmila; Reck, Martin; Thomas, Anish; Pastan, Ira; Parno, Jeff; O’Shannessy, Daniel J.; Fatato, Penny; Maltzman, Julia D.; Wallin, Bruce A.

    2014-01-01

    Purpose Amatuximab is a chimeric monoclonal antibody to mesothelin, a cell surface glycoprotein highly expressed in malignant pleural mesothelioma (MPM). Based on its synergy with chemotherapy in pre-clinical studies, we evaluated the antitumor activity of amatuximab plus pemetrexed and cisplatin in patients with unresectable MPM. Experimental Design In a single-arm phase II study, amatuximab 5 mg/kg was administered on days 1 and 8 with pemetrexed, 500 mg/m2 and cisplatin, 75 mg/m2 on day 1 of 21-day cycles for up to 6 cycles. Patients with response or stable disease received amatuximab maintenance until disease progression. Primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were overall survival (OS), response rate and safety. Results Eighty nine patients were enrolled at 26 centers. Median of five cycles (range 1–6) of combination treatment was administered and 56 (63%) patients received amatuximab maintenance. Combination therapy resulted in no overlapping toxicities. Eleven patients (12.4%) had amatuximab-related hypersensitivity reactions. Responses included partial responses in 33 (40%) and stable disease in 42 (51%). Six month-PFS rate was 51% (95% CI: 39.1, 62.3), median PFS 6.1 months (95% CI: 5.8, 6.4) and median OS 14.8 months (95% CI: 12.4, 18.5) with 29 patients alive at data cut-off. Conclusions Amatuximab with pemetrexed and cisplatin was well-tolerated with objective tumor response or stable disease rate of 90% by independent radiological review. Although PFS was not significantly different from historical controls, the median OS was 14.8 months with a third of patients alive and 5 continuing to receive amatuximab at the time of analysis. PMID:25231400

  10. Clinical effect of pemetrexed as the first‐line treatment in Chinese patients with advanced anaplastic lymphoma kinase‐positive non‐small cell lung cancer

    PubMed Central

    Ma, Di; Hao, Xuezhi; Wang, Yan; Xing, Puyuan

    2016-01-01

    Background The efficacy of pemetrexed‐based first‐line chemotherapy in anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC) has been demonstrated in several studies; however, there is a lack of data from Chinese populations. Methods The clinicopathological characteristics and treatment outcomes of 52 patients with ALK‐positive advanced NSCLC who received pemetrexed as first‐line chemotherapy at the Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively reviewed. The primary end points were response rate and progression‐free survival (PFS). Results The gender proportion was balanced and the median age was 51 years (range 26–76). Of the 52 patients, 46 (88.5%) had stage IV disease, predominantly adenocarcinoma (98.1%). Sixteen patients were current/former smokers and 36 were never/light smokers. The most common sites of metastasis were the pleura (36.5%), bone (30.8%), lung (26.9%), and brain (17.3%). The median PFS was 9.5 months (95% confidence interval 7.454–11.536). At the time of analysis, partial remission was achieved in 18 (34.6%) patients, stable disease in 26 (50.0%), and progressive disease in eight (15.4%); none of the patients achieved complete remission. The objective response rate was 34.6% and the disease control rate was 84.6%. Common adverse events with pemetrexed were neutropenia (53.8%), nausea and vomiting (51.9%), leukopenia (32.7%), and fatigue (25.0%), mainly at grades 1 or 2. Conclusions Pemetrexed is efficient and tolerated as first‐line treatment for ALK‐positive NSCLC in a cohort of Chinese patients and may prove to be an alternative option for the treatment of ALK‐positive NSCLC. PMID:27385988

  11. Efficacy and Safety of Zoledronic Acid and Pamidronate Disodium in the Treatment of Malignant Skeletal Metastasis: A Meta-Analysis.

    PubMed

    Yang, Liqing; Du, Shuai

    2015-10-01

    Solid tumors frequently metastasize to bone. Two bisphosphonates have been investigated for bone metastases including pamidronate disodium and zoledronic acid.By searching the PubMed, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) databases, we conducted a meta-analysis to determine the efficacy and safety of zoledronic acid compared with pamidronate disodium in reducing pain in patients with bone metastases.Studies were pooled, and the relative risk (RR) and its corresponding 95 % confidence interval (CI) were calculated. Version 12.0 STATA software was used for statistical analysis. Twenty relevant articles were included for this meta-analysis study.The complete response rate in cancer patients treatment with zoledronic acid was significantly higher than that with pamidronate disodium (relative risk [RR] = 1.32 [95% confidence interval (CI), 1.00-1.75]; P = 0.987, I = 0%). However, there was no significant difference in the rate of partial response rate (RR = 1.04, 95% CI: 0.90-1.20; P = 0.942, I = 0%) and in the total effective rate (RR = 1.06, 95% CI: 1.00-1.12; P = 0.998, I = 0%). For adverse events (AE), the incidence of headache in cancer patients with zoledronic acid was significantly lower than that with pamidronate disodium (RR = 0.82, 95% CI: 0.70-0.96; P = 0.793, I = 0%). There was no significant difference in nausea or vomiting (RR = 1.00, 95% CI: 0.92-1.09; P = 0.494, I = 0%), fever (RR = 0.98, 95% CI: 0.85-1.14; P =0.633, I = 0%), fatigue (RR = 1.01, 95% CI: 0.91-1.11; P = 0.914, I = 0%) and anorexia (RR = 1.31, 95% CI: 0.91-1.87; P = 0.024, I = 64.4%).In conclusion, this meta-analysis indicates that treatment with zoledronic acid was more effective than pamidronate disodium in the complete response assessments and the incidence of headache, an AE, was significantly lower in cancer patients with zoledronic acid. PMID:26496320

  12. PointBreak: A Randomized Phase III Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB or IV Nonsquamous Non–Small-Cell Lung Cancer

    PubMed Central

    Patel, Jyoti D.; Socinski, Mark A.; Garon, Edward B.; Reynolds, Craig H.; Spigel, David R.; Olsen, Mark R.; Hermann, Robert C.; Jotte, Robert M.; Beck, Thaddeus; Richards, Donald A.; Guba, Susan C.; Liu, Jingyi; Frimodt-Moller, Bente; John, William J.; Obasaju, Coleman K.; Pennella, Eduardo J.; Bonomi, Philip; Govindan, Ramaswamy

    2013-01-01

    Purpose PointBreak (A Study of Pemetrexed, Carboplatin and Bevacizumab in Patients With Nonsquamous Non-Small Cell Lung Cancer) compared the efficacy and safety of pemetrexed (Pem) plus carboplatin (C) plus bevacizumab (Bev) followed by pemetrexed plus bevacizumab (PemCBev) with paclitaxel (Pac) plus carboplatin (C) plus bevacizumab (Bev) followed by bevacizumab (PacCBev) in patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). Patients and Methods Patients with previously untreated stage IIIB or IV nonsquamous NSCLC and Eastern Cooperative Oncology Group performance status of 0 to 1 were randomly assigned to receive pemetrexed 500 mg/m2 or paclitaxel 200 mg/m2 combined with carboplatin area under the curve 6 and bevacizumab 15 mg/kg every 3 weeks for up to four cycles. Eligible patients received maintenance until disease progression: pemetrexed plus bevacizumab (for the PemCBev group) or bevacizumab (for the PacCBev group). The primary end point of this superiority study was overall survival (OS). Results Patients were randomly assigned to PemCBev (n = 472) or PacCBev (n = 467). For PemCBev versus PacCBev, OS hazard ratio (HR) was 1.00 (median OS, 12.6 v 13.4 months; P = .949); progression-free survival (PFS) HR was 0.83 (median PFS, 6.0 v 5.6 months; P = .012); overall response rate was 34.1% versus 33.0%; and disease control rate was 65.9% versus 69.8%. Significantly more study drug–related grade 3 or 4 anemia (14.5% v 2.7%), thrombocytopenia (23.3% v 5.6%), and fatigue (10.9% v 5.0%) occurred with PemCBev; significantly more grade 3 or 4 neutropenia (40.6% v 25.8%), febrile neutropenia (4.1% v 1.4%), sensory neuropathy (4.1% v 0%), and alopecia (grade 1 or 2; 36.8% v 6.6%) occurred with PacCBev. Conclusion OS did not improve with the PemCBev regimen compared with the PacCBev regimen, although PFS was significantly improved with PemCBev. Toxicity profiles differed; both regimens demonstrated tolerability. PMID:24145346

  13. High-Dose Recombinant Interferon Alfa-2B, Ipilimumab, or Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery

    ClinicalTrials.gov

    2016-09-14

    Metastatic Non-Cutaneous Melanoma; Non-Cutaneous Melanoma; Recurrent Melanoma of the Skin; Recurrent Non-Cutaneous Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck

  14. Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQ™) on Cognitive Functions.

    PubMed

    Itoh, Yuji; Hine, Kyoko; Miura, Hiroshi; Uetake, Tatsuo; Nakano, Masahiko; Takemura, Naohiro; Sakatani, Kaoru

    2016-01-01

    Pyrroloquinoline quinone (PQQ) is a quinone compound first identified in 1979. It has been reported that rats fed a PQQ-supplemented diet showed better learning ability than controls, suggesting that PQQ may be useful for improving memory in humans. In the present study, a randomized, placebo-controlled, double-blinded study to examine the effect of PQQ disodium salt (BioPQQ™) on cognitive functions was conducted with 41 elderly healthy subjects. Subjects were orally given 20 mg of BioPQQ™ per day or placebo, for 12 weeks. For cognitive functions, selective attention by the Stroop and reverse Stroop test, and visual-spatial cognitive function by the laptop tablet Touch M, were evaluated. In the Stroop test, the change of Stroop interference ratios (SIs) for the PQQ group was significantly smaller than for the placebo group. In the Touch M test, the stratification analyses dividing each group into two groups showed that only in the lower group of the PQQ group (initial score<70), did the score significantly increase. Measurements of physiological parameters indicated no abnormal blood or urinary adverse events, nor adverse internal or physical examination findings at any point in the study. The preliminary experiment using near-infrared spectrometry (NIRS) suggests that cerebral blood flow in the prefrontal cortex was increased by the administration of PQQ. The results suggest that PQQ can prevent reduction of brain function in aged persons, especially in attention and working memory. PMID:26782228

  15. Phase conjugation by degenerate four wave mixing in disodium fluorescein solution in methanol

    NASA Technical Reports Server (NTRS)

    Abdeldayem, Hossin; Sekhar, P. Chandra; Venkateswarlu, P.; Geroge, M. C.

    1989-01-01

    Organic dyes are known to show the resonant type of nonlinear optical properties, including phase conjugation. In the present work, disodium fluorescein in methanol is used as an organic nonlinear medium for degenerate four wave mixing at 532 nm to see the intensity dependence of the phase conjugate signal at different concentrations of the solution. It is observed that the maximum reflectivity of the signal occurs in a concentration range of 5 x 10(exp -3)/cu cm to 1.2 x 10(exp -2) g/cu cm. It is also observed that the intensity of the signal drops suddenly to less than half of its maximum outside the concentration range mentioned above. An investigation of the phase conjugate signal intensity by changing the delay time between probe signal and the forward pump is also examined. Briefly discussed is the possibility of population grating in dye liquids as a source of enhancing the third order susceptibility besides the other techniques mentioned in reference. The experiment is done by beam splitting the second harmonic (532 nm) of Nd:YAG laser, Q-switched at 20 pulses/sec (pulse width is approximately 8 and 200 mJ per pulse).

  16. Phase behavior of chromonic liquid crystal mixtures of Sunset Yellow and Disodium Cromoglycate

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Akihiro; Smith, Gregory; Yi, Youngwoo; Xu, Charles; Biffi, Silvia; Serra, Francesca; Bellini, Tommaso; Clark, Noel

    2014-03-01

    Chromonic liquid crystals (CLCs) are formed when planar molecules dissolved in water stack into rod-like aggregates that can order as liquid crystals. Isotropic, nematic, and M-phases can be observed depending on the degree of molecular orientational and positional order by variation of the CLC concentration. We focused on mixtures of two well-known CLCs, Sunset Yellow, a food dye, and disodium cromoglycate (DSCG), an asthma medication. In order to study the phase behaviors of these mixtures, we observed their textures in glass cells and capillaries using polarized light microscopy. We report here a ternary phase diagram describing the complete phase behavior of the CLC mixtures. We observed a variety of phase behaviors depending on species ratio and concentration. In the isotropic phase, no clear phase separation of the two dyes was observed, while separation did occur in many nematic and M-phase combinations. We will also describe phase observations made using a light spectroscopy and bulk centrifugal partitioning. Grant support: NSF DMR 1207606 and NSF MRSEC DMR-0820579.

  17. Hypertrophic osteoarthropathy presenting as unilateral cellulitis with successful treatment using pamidronate disodium.

    PubMed

    Bernardo, Sebastian G; Emer, Jason J; Burnett, Mark E; Gordon, Marsha

    2012-09-01

    Hypertrophic pulmonary osteoarthropathy is a paraneoplastic syndrome seen in patients with lung cancer. This condition is characterized by the presence of digital clubbing, periosteal thickening, synovial thickening, and severe pain of the affected joints. Other syndromes exhibiting clubbing may or may not have underlying diseases causing their manifestation. An example is primary hypertrophic osteoarthropathy, or pachydermoperiostosis. While clubbing makes up part of the clinical picture in both hypertrophic pulmonary osteoarthropathy and hypertrophic osteoarthropathy, the latter has no underlying disease associations. Rather, primary hypertrophic osteoarthropathy is familial, idiopathic, and has a chronic course often beginning during puberty in males. Secondary hypertrophic osteoarthropathy is an acquired form of clubbing that is classically associated with lung disease. However, it has also been associated with diseases of the heart, liver, and intestines. In the setting of pulmonary malignancy, secondary hypertrophic osteoarthropathy is known as hypertrophic pulmonary osteoarthropathy. Hypertrophic pulmonary osteoarthropathy has a distinct constellation of clinical findings that includes intractable pain often refractory to treatments other than resolution of the underlying disease process. The authors herein report a case of hypertrophic pulmonary osteoarthropathy masquerading as recurrent lower extremity cellulitis with chronic hand and foot pain in the setting of pulmonary malignancy that responded dramatically to intravenous pamidronate disodium (a bisphosphonate). Given the rarity of hypertrophic osteoarthropathy associated with lung cancer and the difficulty with pain management in such circumstances, the authors present the following case in which pain was mitigated by treatment with bisphosphonate therapy. PMID:23050033

  18. Plasma concentrations of disodium cromoglycate after various inhalation methods in healthy subjects

    PubMed Central

    Kato, Y; Muraki, K; Fujitaka, M; Sakura, N; Ueda, K

    1999-01-01

    Aims To compare the plasma concentrations of disodium cromoglycate (DSCG) following various inhalation procedures in healthy volunteers. Methods Nine healthy subjects inhaled 2 mg of aerosol, 20 mg of nebuliser solution only, 20 mg of nebuliser solution mixed with isotonic saline, or 20 mg of nebuliser solution mixed with saline and procaterol, a β2-adenoceptor agonist, on separate occasions 2–3 weeks apart. Plasma concentrations of DSCG were determined by high-performance liquid chromatography (h.p.l.c.). Results The peak plasma concentrations of DSCG were 1.5±0.7 (range 0.4–2.4) ng ml−1 in the aerosol group, 8.8±6.2 (range 5.3–19.9) ng ml−1 in the nebuliser solution only group, 17.2±16.3 (range 5.0–38.6) ng ml−1 in the nebuliser solution plus isotonic saline group, and 24.5±11.9 (range 10.2–44.9) ng ml−1 in the nebuliser solution plus saline and procaterol group. Thus subjects who used the nebuliser had markedly higher plasma concentrations of DSCG than subjects who used the aerosol inhaler. Conclusions These findings may have important implications for the evaluation of inhalation treatment with DSCG for bronchial asthma. PMID:10417491

  19. In vitro and in vivo inhibitory effects of disodium cromoglycate on influenza virus infection.

    PubMed

    Hidari, Kazuya I P J; Tsujii, Eisaku; Hiroi, Jun; Mano, Eriko; Miyatake, Akihiko; Miyamoto, Daisei; Suzuki, Takashi; Suzuki, Yasuo

    2004-06-01

    Disodium cromoglycate (DSCG) is one of the safest drugs for the prevention of bronchial asthma and allergic rhinitis attacks. The effect of DSCG on acute upper respiratory tract viral infection is still controversial. Here we investigated DSCG inhibition of influenza virus infection in vivo and in vitro. In vivo effects of DSCG on viral infection were assessed using a murine model of respiratory tract infection. Intranasal administration of DSCG protected mice from death induced by infection with influenza virus A/PR/8/34. We analyzed DSCG anti-viral effects in vitro by either (i) treating cells prior to viral adsorption, (ii) treating cells concurrently with viral adsorption, or (iii) treating cells after viral adsorption. DSCG treatment of cells during or after, but not before, viral adsorption significantly inhibited influenza viral infection, indicating DSCG acts on events late in viral infection. DSCG exerts anti-influenza effect both in vitro and in vivo at the doses compatible with treatment for asthma. DSCG marginally inhibited influenza viral neuraminidase and membrane fusion functions, suggesting that DSCG inhibition of viral neuraminidase and fusion activities may partially mediate this anti-influenza effect. Our results indicate that treatment of patients including children with DSCG may take advantages for prevention from influenza virus infection. PMID:15187427

  20. Modification of disodium cromoglycate passage across lung epithelium in vitro via incorporation into polymeric microparticles.

    PubMed

    Haghi, Mehra; Salama, Rania; Traini, Daniela; Bebawy, Mary; Young, Paul M

    2012-03-01

    Two microparticle systems containing disodium cromoglycate (DSCG) alone or with polyvinyl alcohol (DSCG/PVA) were produced via spray drying and compared in terms of their physicochemical characteristics, aerosol performance and drug uptake across a pulmonary epithelial cell line (Calu-3), cultured under air interface conditions. The particle size distribution of DSCG and DSCG/PVA were similar, of spherical geometry, amorphous and suitable for inhalation purposes. Aerosolisation studies using a modified twin-stage impinger showed the DSCG/PVA to have greater aerosol performance than that of DSCG alone. Aerosol particles of DSCG and DSCG/PVA were deposited onto the surface of the Calu-3 air interface epithelium monolayer and the drug uptake from apical to basal directions measured over time. Drug uptake was measured across a range of doses to allow comparison of equivalent drug and powder mass deposition. Analysis of the data indicated that the percentage cumulative drug uptake was independent of the mass of powder deposited, but dependent on the formulation. Specifically, with the formulation containing DSCG, the diffusion rate was observed to change with respect to time (indicative of a concentration-dependent diffusion process), whilst DSCG/PVA showed a time-independent drug uptake (suggesting a zero-order depot release). PMID:22203523

  1. Effect of reproterol either alone or combined with disodium cromoglycate on airway responsiveness to methacholine.

    PubMed

    Kanniess, Frank; Jörres, Rudolf A; Magnussen, Helgo

    2005-01-01

    Regular use of inhaled beta2-agonists might lead to tolerance as reflected in a loss of bronchoprotection. In vitro-data suggest that this might be prevented by disodium cromoglycate (DSCG). Therefore, we studied the effect of the beta2-agonist reproterol in combination with DSCG. In a cross-over design, 19 subjects with airway hyperresponsiveness inhaled either placebo, 1mg reproterol, 2 mg DSCG, or 1mg reproterol plus 2 mg DSCG 4x daily over 2 weeks. Treatment periods were separated by > or = 7 days. Before and at the end of periods, lung function and methacholine responsiveness were determined in the morning, and 6h later the bronchodilator effect and the protection against methacholine-induced bronchoconstriction. Reproterol or DSCG or their combination did not exert detrimental effects on lung function, airway responsiveness, or bronchodilator capacity. However, bronchoprotection was significantly reduced (p < 0.05) after treatment with placebo, reproterol or reproterol plus DSCG, the respective changes being 0.59, 0.96 and 1.37 doubling concentrations. All changes were small as compared to intraindividual variability. In this model all treatments except with DSCG caused a significant but small loss of protection against methacholine-induced bronchoconstriction. Thus, tolerance was not prevented by 2 weeks of additional treatment with DSCG, in contrast to in vitro findings. PMID:15939309

  2. Disodium cromoglycate attenuates hypoxia induced enlargement of end-expiratory lung volume in rats.

    PubMed

    Maxová, H; Hezinová, A; Vízek, M

    2011-01-01

    Mechanism responsible for the enlargement of end-expiratory lung volume (EELV) induced by chronic hypoxia remains unclear. The fact that the increase in EELV persists after return to normoxia suggests involvement of morphological changes. Because hypoxia has been also shown to activate lung mast cells, we speculated that they could play in the mechanism increasing EELV similar role as in vessel remodeling in hypoxic pulmonary hypertension (HPH). We, therefore, tested an effect of mast cells degranulation blocker disodium cromoglycate (DSCG) on hypoxia induced EELV enlargement. Ventilatory parameters, EELV and right to left heart weight ratio (RV/LV+S) were measured in male Wistar rats. The experimental group (H+DSCG) was exposed to 3 weeks of normobaric hypoxia and treated with DSCG during the first four days of hypoxia, control group was exposed to hypoxia only (H), two others were kept in normoxia as non-treated (N) and treated (N+DSCG) groups. DSCG treatment significantly attenuated the EELV enlargement (H+DSCG = 6.1+/-0.8; H = 9.2+/-0.9; ml +/-SE) together with the increase in minute ventilation (H + DSCG = 190+/-8; H = 273 +/- 10; ml/min +/- SE) and RV/LV + S (H + DSCG = 0.39 +/- 0.03; H = 0.50 +/- 0.06). PMID:22106819

  3. Acute and subchronic toxicity studies of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) in rats.

    PubMed

    Nakano, Masahiko; Takahashi, Hisaaki; Koura, Seiko; Chung, Catherine; Tafazoli, Shahrzad; Roberts, Ashley

    2014-10-01

    The potential use of pyrroloquinoline quinone disodium salt (BioPQQ™), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ™ was shown to be 1000-2000mg/kg body weight (bw) in male and 500-1000mg/kgbw in female rats. In the 14-day study, high doses of BioPQQ™ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100mg/kgbw/day was determined for BioPQQ™ in rats, the highest dose tested in the 13-week study. PMID:24995591

  4. Evaluation of liver function using gadoxetate disodium (Gd-EOB-DTPA) enhanced MR imaging

    NASA Astrophysics Data System (ADS)

    Yamada, Akira; Hara, Takeshi; Li, Feng; Doi, Kunio

    2010-03-01

    Indocyanine green (ICG) is widely used for its clearance test in the evaluation of liver function. Gadoxetate disodium (Gd-EOB-DTPA) is a targeted MR contrast agent partially taken up by hepatocytes. The objective of this study was to evaluate the feasibility of an estimation of the liver function corresponding to plasma disappearance rate of indocyanine green (ICG-PDR) by use of the signal intensity of the liver alone in Gd-EOB-DTPA enhanced MR imaging (EOB-MRI). We evaluated fourteen patients who had EOB-MRI and ICG clearance test within 1 month. 2D-GRE T1 weighted images were obtained at pre contrast, 3 min (equilibrium phase) and 20 min (hepatobiliary phase) after the intravenous administration of Gd-EOB-DTPA, and the mean signal intensity of the liver was measured. The correlation between ICG-PDR and many parameters derived from the signal intensity of the liver in EOB-MRI was evaluated. The correlation coefficient between ICG-PDR and many parameters derived from the signal intensity of the liver in EOBMRI was low and not significant. The estimation of the liver function corresponding to ICG-PDR by use of the signal intensity of the liver alone in EOB-MRI would not be reliable.

  5. Brain Efflux Index To Investigate the Influence of Active Efflux on Brain Distribution of Pemetrexed and Methotrexate

    PubMed Central

    Li, Li; Agarwal, Sagar

    2013-01-01

    Antifolates, in particular methotrexate (MTX), have been widely used in the treatment of primary and secondary tumors of the central nervous system (CNS). Pemetrexed (PMX) is a novel antifolate that also exhibits potent antitumor activity against CNS malignancies. Studies have shown that brain distribution of both antifolates is significantly restricted, possible due to active efflux transport at the blood-brain barrier (BBB). This study characterizes the brain-to-blood transport of PMX and MTX and examines the role of several efflux transporters in brain distribution of the antifolates by use of the intracerebral microinjection technique (brain efflux index). The results from this study show that both PMX and MTX undergo saturable efflux transport across the BBB, with elimination half-lives of approximately 39 minutes and 29 minutes, respectively. Of the various efflux transporters this study investigated, multidrug resistance-associated protein 2 (Mrp2) does not play an important role in the brain distribution of the two antifolate drugs. Interestingly, breast-cancer resistance protein (Bcrp) makes a significant contribution to the brain elimination of MTX but not PMX. In addition, the brain-to-blood transport of both antifolates was inhibited by probenecid and benzylpenicillin, suggesting the involvement of organic anion transporters in the efflux of these compounds from the brain, with organic anion transporter 3 (Oat3) being a possibility. Our results suggest that one of the underlying mechanisms behind the limited brain distribution of PMX and MTX is active efflux transport processes at the BBB, including a benzylpenicillin-sensitive transport system and/or the active transporter Bcrp. PMID:23297298

  6. In vitro genotoxicity and cytotoxicity of a particular combination of pemetrexed and cefixime in human peripheral blood lymphocytes.

    PubMed

    Istifli, Erman Salih; Topaktaş, Mehmet

    2015-01-01

    This study aims to find the genotoxic and cytotoxic effects of a particular combination of pemetrexed (PMX) and cefixime (CFX) in human peripheral blood lymphocytes. Chromosome aberration (CA), sister chromatid exchange (SCE), and micronucleus (MN) tests were used to assess genotoxicity. Whereas, the cytotoxicity was evaluated by using mitotic index (MI), proliferation index (PI), and nuclear division index (NDI). Our tests were proceeded with concentrations of 12.5 + 450, 25 + 800, 37.5 + 1150, and 50 + 1500 μg/mL of a mixture of PMX and CFX separately for 24 hr and 48 hr. The combination of PMX + CFX did not induce the CA or SCE in human peripheral blood lymphocytes when compared with both the control and the solvent control. MN in human peripheral blood lymphocytes was not significantly increased after treatment with a particular combination of PMX + CFX. However, PMX + CFX significantly decreased the MI, PI and NDI at all concentrations for 24- and 48-hr treatment periods when compared with both controls. Generally, PMX + CFX inhibited cell proliferation more than positive control (MMC) and showed a higher cytotoxic effect than MMC at both treatment periods. These results were compared with individual effects of PMX and CFX. As a result, it was observed that a particular combination of PMX + CFX was not genotoxic. However, the combination synergistically increase cytotoxicity in human peripheral blood lymphocytes. PMID:25653913

  7. Cost-effectiveness analysis of pemetrexed versus docetaxel in the second-line treatment of non-small cell lung cancer in Spain: results for the non-squamous histology population

    PubMed Central

    2010-01-01

    Background The objective of this study was to conduct a cost-effectiveness evaluation of pemetrexed compared to docetaxel in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) for patients with predominantly non-squamous histology in the Spanish healthcare setting. Methods A Markov model was designed consisting of stable, responsive, progressive disease and death states. Patients could also experience adverse events as long as they received chemotherapy. Clinical inputs were based on an analysis of a phase III clinical trial that identified a statistically significant improvement in overall survival for non-squamous patients treated with pemetrexed compared with docetaxel. Costs were collected from the Spanish healthcare perspective. Results Outcomes of the model included total costs, total quality-adjusted life years (QALYs), total life years gained (LYG) and total progression-free survival (PFS). Mean survival was 1.03 years for the pemetrexed arm and 0.89 years in the docetaxel arm; QALYs were 0.52 compared to 0.42. Per-patient lifetime costs were € 34677 and € 32343, respectively. Incremental cost-effectiveness ratios were € 23967 per QALY gained and € 17225 per LYG. Conclusions Pemetrexed as a second-line treatment option for patients with a predominantly non-squamous histology in NSCLC is a cost-effective alternative to docetaxel according to the € 30000/QALY threshold commonly accepted in Spain. PMID:20113499

  8. Efficacy of cisplatin/pemetrexed with bevacizumab to treat advanced lung adenocarcinoma with different drive genes: case report and literature review

    PubMed Central

    Wang, Haiyong; Zhu, Hui; Kong, Li; Yu, Jinming

    2016-01-01

    Background Bevacizumab combined with chemotherapy has become the first-line therapy in advanced nonsquamous non-small-cell lung cancer (NSCLC). However, few studies have focused on cisplatin/pemetrexed with bevacizumab as the first-line therapy to treat advanced nonsquamous NSCLC. Importantly, whether the epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements can influence the efficacy of bevacizumab in combination with chemotherapy is very interesting. Herein, we report three cases with different types of gene drives in advanced nonsquamous NSCLC. Case presentation In the first case, a patient presented with wild-type EGFR and negative ALK rearrangement. In the second case, a patient presented with wild-type EGFR and positive ALK rearrangement. In the third case, a patient presented with negative ALK rearrangement and mutated EGFR in exon 19. Conclusion We speculate that bevacizumab in combination with cisplatin/pemetrexed as the first-line therapy is well tolerated and results in a clinically meaningful treatment benefit, irrespective of the gene drive type in advanced nonsquamous NSCLC. However, more data are needed to confirm the relationship. PMID:27555784

  9. Comparison of treatment costs of grade 3/4 adverse events associated with erlotinib or pemetrexed maintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) in Germany, France, Italy, and Spain.

    PubMed

    Banz, Kurt; Bischoff, Helge; Brunner, Matthias; Chouaid, Christos; de Castro Carpeño, Javier; de Marinis, Filippo; Grossi, Francesco; Vergnenègre, Alain; Walzer, Stefan

    2011-12-01

    Objective of this indirect economic comparison was to estimate and compare management costs of grade 3/4 adverse events (AEs) reported for first-line erlotinib or pemetrexed maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC). The economic analysis was performed for Germany, France, Italy and Spain. Types and incidences of reported grade 3/4 AEs observed with erlotinib or pemetrexed maintenance therapy were retrieved from two recently published placebo-controlled trials. Country-specific estimates on standard treatment algorithms and incremental medical resource utilization associated with each of the reported grade 3/4 AEs have been obtained from clinical oncologists practicing in the four countries and co-authoring this article. The resource use items were subsequently assigned country-specific tariffs to estimate total per-patients costs associated with the AE profiles of the two compared maintenance regimens. For the economic analysis a customized economic spreadsheet model was employed. Our comparison shows lower total average per-patient AE management costs for erlotinib than for pemetrexed maintenance therapy in all four studied countries. Total estimated cost savings per patient in favour of erlotinib amount to € 121, € 237, € 106, and € 119 for Germany, France, Italy and Spain, respectively. These AE cost savings for erlotinib when compared to pemetrexed represent a decrease by 80%, 71%, 94%, and 82%, respectively. The study also discovered considerable differences in AE management costs across countries which are primarily due to differences in clinician's estimates of hospitalization referral rates. Erlotinib maintenance therapy in patients with advanced NSCLC causes lower AE management costs than pemetrexed maintenance therapy indicating a potentially superior tolerability profile. PMID:21592611

  10. Hsp90 is a direct target of the anti-allergic drugs disodium cromoglycate and amlexanox.

    PubMed

    Okada, Miki; Itoh, Hideaki; Hatakeyama, Takashi; Tokumitsu, Hiroshi; Kobayashi, Ryoji

    2003-09-01

    Hsp90 (heat-shock protein 90) alone can act to prevent protein aggregation and promote refolding in vitro, but in vivo it operates as a part of a multichaperone complex, which includes Hsp70 and cohort proteins. Since the physiological function of Hsp90 is not yet fully understood, the development of specific antagonists might open new lines of investigation on the role of Hsp90. In an effort to discover Hsp90 antagonists, we screened many drugs and found that the anti-allergic drugs DSCG (disodium cromoglycate) and amlexanox target Hsp90. Both drugs were found to bind directly wild-type Hsp90 via the N- and C-terminal domains. Both drugs strongly suppressed the in vitro chaperone activity of native Hsp90 towards citrate synthase at 1.5-3.0 microM. Amlexanox suppressed C-terminal chaperone activity in vitro, but not N-terminal chaperone activity, and inhibited the association of cohort proteins, such as cyclophilin 40 and Hsp-organizing protein, to the C-terminal domain of Hsp90. These data suggest that amlexanox might disrupt the multichaperone complex, including Hsp70 and cohort proteins, both in vitro and in vivo. Although DSCG inhibited the in vitro chaperone activity of the N-terminal domain, the drug had no effect either on the C-terminal chaperone activity or on the association of the cohort proteins with the C-terminus of Hsp90. The physiological significance of these interactions in vivo remains to be investigated further, but undoubtedly must be taken into account when considering the pharmacology of anti-allergic drugs. DSCG and amlexanox may serve as useful tools for evaluating the physiological significance of Hsp90. PMID:12803546

  11. Effect of particle size, air flow and inhaler device on the aerosolisation of disodium cromoglycate powders.

    PubMed

    Chew, N Y; Bagster, D F; Chan, H K

    2000-09-25

    Recently, the dispersion of mannitol powders has demonstrated the importance of particle size, air flow and inhaler device (Chew and Chan, 1999). The aim of the present study is to extend our investigation to a different compound, disodium cromoglycate (DSCG) powders. Solid state characteristics of the powders were assessed by particle sizing, scanning electron microscopy, X-ray powder diffraction, moisture content, particle density determination and freeze fracture. The aerosol behaviour of the powders was studied by dispersion using Rotahaler(R) and Dinkihaler(R), connected to a four-stage liquid impinger operating at 30-120 l/min. Three amorphous powders with a mass median diameter (MMD) of 2.3, 3.7, 5.2 microm and a similar polydispersity were prepared. The particles were nearly spherical with a particle density of 1.6 g/cm(3) and moisture content of 6.6 wt.%. Using Rotahaler(R), the maximum fine particle fraction (FPF(max)) for all three powders was only 15 wt.%, attained at the highest flow of 120 l/min. Using Dinkihaler(R), the FPF(max) was two to four times higher, being 36 and 29 wt.% for the 2.3 and 3.7 microm powder, respectively, at 60 l/min; and 18 wt.% for the 5.2 microm powder at 120 l/min. Hence, the study shows that the FPF in the DSCG powder aerosols was determined by the interaction of the particle size, air flow and inhaler design. The attribution of the amorphous nature and the different physico-chemical properties of the powder may explain the incomplete and low dispersibility of DSCG. PMID:11058812

  12. Inhaled disodium cromoglycate (DSCG) as maintenance therapy in children with asthma: a systematic review

    PubMed Central

    Tasche, M; Uijen, J; Bernsen, R; de Jongste, J C; van der Wouden, J C

    2000-01-01

    BACKGROUND—Disodium cromoglycate (DSCG) is included in the BTS guidelines on the treatment of asthma for use in children, but is now used only infrequently. We have identified and interpreted the findings of all published randomised, placebo controlled trials of DSCG in the prophylactic treatment of children with asthma.
METHODS—Several databases were searched to identify trials. Studies were included if they investigated subjects with asthma aged 0-18 years old, addressed maintenance treatment with inhaled DSCG, and were published in English. The methodological quality of the studies was assessed independently by three reviewers. The 95% confidence intervals (CI) of differences in the treatment effect for cough and wheeze between placebo and treatment with DSCG were computed. The estimates were pooled and tested for homogeneity and, to assess possible publication bias, a funnel plot was made and tested for symmetry.
RESULTS—Of the 24 randomised, placebo controlled trials identified, the methodological scores varied widely. The null hypothesis of homogeneity was rejected. Under the assumption of heterogeneity the overall CI for wheeze was 0.11 to 0.26 and for cough was 0.13to 0.27. The overall tolerance intervals (-0.11 to 0.48 and -0.04 to 0.43 for wheeze and cough, respectively) both included zero, so it cannot be concluded that future studies will show an effect of DSCG compared with placebo. Older studies were more often in favour of DSCG. The funnel plots suggest publication bias; small studies with negative or equal outcomes are lacking.
CONCLUSION—Given the apparent publication bias, the small overall treatment effect, and the tolerance interval including zero, there is insufficient evidence that DSCG has a beneficial effect as maintenance treatment in children with asthma.

 PMID:11050259

  13. Hsp90 is a direct target of the anti-allergic drugs disodium cromoglycate and amlexanox.

    PubMed Central

    Okada, Miki; Itoh, Hideaki; Hatakeyama, Takashi; Tokumitsu, Hiroshi; Kobayashi, Ryoji

    2003-01-01

    Hsp90 (heat-shock protein 90) alone can act to prevent protein aggregation and promote refolding in vitro, but in vivo it operates as a part of a multichaperone complex, which includes Hsp70 and cohort proteins. Since the physiological function of Hsp90 is not yet fully understood, the development of specific antagonists might open new lines of investigation on the role of Hsp90. In an effort to discover Hsp90 antagonists, we screened many drugs and found that the anti-allergic drugs DSCG (disodium cromoglycate) and amlexanox target Hsp90. Both drugs were found to bind directly wild-type Hsp90 via the N- and C-terminal domains. Both drugs strongly suppressed the in vitro chaperone activity of native Hsp90 towards citrate synthase at 1.5-3.0 microM. Amlexanox suppressed C-terminal chaperone activity in vitro, but not N-terminal chaperone activity, and inhibited the association of cohort proteins, such as cyclophilin 40 and Hsp-organizing protein, to the C-terminal domain of Hsp90. These data suggest that amlexanox might disrupt the multichaperone complex, including Hsp70 and cohort proteins, both in vitro and in vivo. Although DSCG inhibited the in vitro chaperone activity of the N-terminal domain, the drug had no effect either on the C-terminal chaperone activity or on the association of the cohort proteins with the C-terminus of Hsp90. The physiological significance of these interactions in vivo remains to be investigated further, but undoubtedly must be taken into account when considering the pharmacology of anti-allergic drugs. DSCG and amlexanox may serve as useful tools for evaluating the physiological significance of Hsp90. PMID:12803546

  14. Effects of Pyrroloquinoline Quinone Disodium Salt Intake on the Serum Cholesterol Levels of Healthy Japanese Adults.

    PubMed

    Nakano, Masahiko; Kawasaki, Yuuki; Suzuki, Naoko; Takara, Tsuyoshi

    2015-01-01

    Pyrroloquinoline quinone (PQQ) is a water-soluble quinone compound that has a strong anti-oxidant capacity. A previous study in rats fed a PQQ-depleted diet showed that elevated levels of serum triglyceride (TG) decreased after PQQ supplementation. However, there is only one study reporting the effects of PQQ on serum lipid levels, such as those of TG and cholesterol, in humans. In this study, the effects of PQQ disodium salt (BioPQQ™) on serum TG and cholesterol levels in humans after 6 and 12 wk of treatment at an oral dosage of 20 mg/d were examined. This trial was conducted according to a randomized, placebo-controlled, double-blinded protocol. A total of 29 healthy Japanese adults, ranging from 40 to 57 y old, with normal to moderately high TG levels (110-300 mg/dL) as measured by a recent blood examination, were included in this study. In eleven volunteers out of 29, serum low-density lipoprotein cholesterol (LDL-chol) levels at baseline were high (≥140 mg/dL). After 12 wk, the mean serum TG levels had not changed; however, a marginally significant decrease in the mean LDL-chol (from 136.1 to 127.0 mg/dL) was observed in the PQQ group. In the stratification analysis of the high LDL-chol subgroup (baseline LDL-chol level ≥140 mg/dL), the mean LDL-chol levels decreased significantly from the baseline values in the PQQ group compared to the placebo group. Our study findings suggest that PQQ suppressed the LDL-chol level, which is an important finding, because a high level of this lipid is a risk factor for various lifestyle-related diseases. PMID:26226960

  15. A phase II study of pemetrexed plus carboplatin followed by maintenance pemetrexed as first-line chemotherapy for elderly patients with advanced non-squamous non-small cell lung cancer.

    PubMed

    Tamiya, Motohiro; Tamiya, Akihiro; Kaneda, Hiroyasu; Nakagawa, Kazuhiko; Yoh, Kiyotaka; Goto, Koichi; Okamoto, Hiroaki; Shimokawa, Tsuneo; Abe, Tetsuya; Tanaka, Hiroshi; Daga, Haruko; Takeda, Koji; Hirashima, Tomonori; Atagi, Shinji

    2016-01-01

    A phase I study recommended carboplatin (CBDCA, area under the curve = 5) plus pemetrexed (PEM, 500 mg/m(2)) for elderly patients (≥75-years old) with non-squamous non-small cell lung cancer (NSCLC). PEM maintenance therapy was well tolerated. We conducted a multicenter phase II trial to evaluate the efficacy and safety of this regimen in elderly patients with NSCLC. Four courses of CBDCA plus PEM, followed by PEM, were administered. The primary endpoint was the 1-year overall survival (OS) rate, and the secondary endpoints were OS, progression-free survival (PFS), response rate (RR), and safety. Thirty-four patients (median age, 77 years) were enrolled between June 2012 and May 2013. The median observation time was 22.7 months. The primary endpoint of the 1-year OS rate was 58.0 % (95 % confidence interval (CI) 42.9-78.4 %), and RR and disease control rate were 41.2 and 85.3 %, respectively. Fourteen patients had partial responses, 15 had stable disease, 4 had disease progression, and 1 was not evaluated. The maintenance therapy rate was 58.8 %. The median PFS was 5.7 months (95 % CI 3.9-8.9 months), and median OS was 20.5 months (95 % CI 10.0-infinity months). Grade ≥3 hematological adverse events included leucopenia (23.5 % of patients), neutropenia (55.9 %), anemia (35.3 %), and thrombocytopenia (20.6 %). Grade ≥3 non-hematological adverse events included febrile neutropenia (8.8 %), elevated aminotransferases (5.9 %), infection (23.5 %), and anorexia/fatigue (5.9 %). Four patients had interstitial lung diseases (ILD) and one died due to ILD. CBDCA plus PEM, followed by PEM, was effective and reasonably tolerated in chemotherapy-naïve elderly patients with non-squamous NSCLC. Clinical Trial Registration This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (Trial Number UMIN 000004810). PMID:26603297

  16. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-11-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: Abatacept, Adalimumab, AdCD40L, Adefovir, Aleglitazar, Aliskiren fumarate, AM-103, Aminolevulinic acid methyl ester, Amlodipine, Anakinra, Aprepitant, Aripiprazole, Atazanavir sulfate, Axitinib; Belimumab, Bevacizumab, Bimatoprost, Bortezomib, Bupropion/naltrexone; Calcipotriol/betamethasone dipropionate, Certolizumab pegol, Ciclesonide, CYT-997; Darbepoetin alfa, Darunavir, Dasatinib, Desvenlafaxine succinate, Dexmethylphenidate hydrochloride cogramostim; Eltrombopag olamine, Emtricitabine, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus-eluting coronary stent, Exenatide, Ezetimibe; Fenretinide, Filibuvir, Fludarabine; Golimumab; Hepatitis B hyperimmunoglobulin, HEV-239, HP-802-247, HPV-16/18 AS04, HPV-6/11/16/18, Human albumin, Human gammaglobulin; Imatinib mesylate, Inotuzumab ozogamicin, Invaplex 50 vaccine; Lapatinib ditosylate, Lenalidomide, Liposomal doxorubicin, Lopinavir, Lumiliximab, LY-686017; Maraviroc, Mecasermin rinfabate; Narlaprevir; Ocrelizumab, Oral insulin, Oritavancin, Oxycodone hydrochloride/naloxone; Paclitaxel-eluting stent, Palonosetron hydrochloride, PAN-811, Paroxetine, Pazopanib hydrochloride, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Pitavastatin calcium, Posaconazole, Pregabalin, Prucalopride succinate; Raltegravir potassium, Ranibizumab, RHAMM R3 peptide, Rosuvastatin calcium; Salclobuzic acid sodium salt, SCY-635, Selenate sodium, Semapimod hydrochloride, Silodosin, Siltuximab, Silybin, Sirolimus-eluting stent, SIR-Spheres, Sunitinib malate; Tapentadol hydrochloride, Tenofovir disoproxil

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab, BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B, BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride, CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa, desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA-paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated), duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569, elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI-2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab, ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184, semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin

  18. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Activated protein C concentrate, Ad-CD154, Adeno-Interferon gamma, alemtuzumab, APC-8024, 9-aminocamptothecin, aprepitant, l-arginine hydrochloride, aripiprazole, arsenic trioxide, asimadoline; O6-Benzylguanine, bevacizumab, Bi-20, binodenoson, biphasic insulin aspart, bivatuzumab, 186Re-bivatuzumab, BMS-181176, bosentan, botulinum toxin type B, BQ-123, bryostatin 1; Carboxy- amidotriazole, caspofungin acetate, CB-1954, CC-4047, CDP-860, cerivastatin sodium, clevidipine, CTL-102; 3,4-DAP, darbepoetin alfa, decitabine, desloratadine, DHA-paclitaxel, duloxetine hydrochloride; Efalizumab, EGF vaccine, eletriptan, eniluracil, ENMD-0997, eplerenone, eplivanserin, erlosamide, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, eszopiclone, everolimus, exatecan mesilate, exenatide, ezetimibe; Fondaparinux sodium, FR-901228, FTY-720; Gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride; Hexyl insulin M2, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, iodine (I131) tositumomab, ISV-205, ivabradine hydrochloride, ixabepilone; Levetiracetam, levocetirizine, linezolid, liposomal NDDP, lonafarnib, lopinavir, LY-156735; Mafosfamide cyclohexylamine salt, magnesium sulfate, maxacalcitol, meclinertant, melagatran, melatonin, MENT, mepolizumab, micafungin sodium, midostaurin, motexafin gadolinium; Nesiritide, NS-1209, NSC-601316, NSC-683864; Osanetant; Palonosetron hydrochloride, parecoxib sodium, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegylated OB protein, pemetrexed disodium, perillyl alcohol, picoplatin, pimecrolimus, pixantrone maleate, plevitrexed

  19. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com This issue focuses on the following selection of drugs: A-007, A6, adalimumab, adenosine triphosphate, alefacept, alemtuzumab, AllerVax Ragweed, amphora, anakinra, angiotensin-(1-7), anidulafungin, apomine, aripiprazole, atomoxetine hydrochloride, avanafil; BAL-8557, becatecarin, bevacizumab, biphasic insulin aspart, BMS-188797, bortezomib, bosentan, botulinum toxin type B, brivudine; Calcipotriol/betamethasone dipropionate, caspofungin acetate, catumaxomab, certolizumab pegol, cetuximab, CG-0070, ciclesonide, cinacalcet hydrochloride, clindamycin phosphate/benzoyl peroxide, cryptophycin 52, Cypher; Dabigatran etexilate, darapladib, darbepoetin alfa, decitabine, deferasirox, desloratadine, dexanabinol, dextromethorphan/quinidine sulfate, DMF, drotrecogin alfa (activated), duloxetine hydrochloride; E-7010, edaravone, efalizumab, emtricitabine, entecavir, eplerenone, erlotinib hydrochloride, escitalopram oxalate, estradiol valerate/dienogest, eszopiclone, exenatide, ezetimibe; Fondaparinux sodium, fulvestrant; Gefitinib, gestodene, GYKI-16084; Hyaluronic acid, hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, indiplon, insulin glargine; Juzen-taiho-to; Lamivudine/zidovudine/abacavir sulfate, L-arginine hydrochloride, lasofoxifene tartrate, L-BLP-25, lenalidomide, levocetirizine, levodopa/carbidopa/entacapone, lexatumumab, lidocaine/prilocaine, lubiprostone, lumiracoxib; MAb-14.18, mitoquidone; Natalizumab, neridronic acid, neuradiab; Olpadronic acid sodium salt, omalizumab; p53-DC vaccine, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, perifosine, pimecrolimus, prasterone, prasugrel, PRO-2000

  20. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine

  1. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2007-10-01

    (-)-Epigallocatechin gallate, [188Re]-P2045, 12B75, 89-12; Abacavir sulfate/lamivudine, Abatacept, Abiraterone acetate, ABT-869, Adalimumab, Ad-rh Endostatin, AI-700, Alemtuzumab, Alvimopan hydrate, Amrubicin hydrochloride, AP-12009, Apomab 7.3, Arformoterol tartrate, Aripiprazole, AS-1404, Azacitidine, AZD-0530; Bevacizumab, BHT-3009, Biapenem, Bortezomib, Bosentan, Bremelanotide; CA9-SCAN, Calcitonin gene-related peptide, Canertinib dihydrochloride, Cannabidiol, Carboxyamidotriazole, Caspofungin acetate, Celgosivir, Certolizumab pegol, Cinacalcet hydrochloride, Clevudine, CP-751871, Curcumin, Cx-401, Cypher; Darunavir, Decitabine, Deforolimus, Dexamet, Dipyridamole/prednisolone, Drospirenone, Drospirenone/estradiol, DTPw-HepB-Hib, Duloxetine hydrochloride; Efalizumab, Emtricitabine, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone; Ferumoxtran-10, Ferumoxytol, Fondaparinux sodium, Fosaprepitant dimeglumine; gamma-Hydroxybutyrate sodium, Gefitinib, Genistein, Ghrelin (human), Gimatecan, GM-CSF PMED, Golimumab, gp100 PMED; Imatinib mesylate, Immunoglobulin intravenous (human), IV Gamma-globulin; LA-419, Laropiprant, L-BLP-25, Levodopa/carbidopa/entacapone, Lidocaine/prilocaine, Lopinavir/ritonavir, Lumiracoxib, LY-2076962; Mepolizumab, Methylnaltrexone bromide, Mitiglinide calcium hydrate, Mycophenolic acid sodium salt, Myristyl nicotinate; Natalizumab, Nesiritide, Niacin/lovastatin; Oblimersen sodium, Ofatumumab, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide, Ozarelix; Palonosetron hydrochloride, Parathyroid hormone (human recombinant), Pazopanib hydrochloride, Pegaptanib octasodium, Pegfilgrastim, Peginterferon alfa- 2a, Peginterferon alfa-2b, Pegvisomant, Pemetrexed disodium, Pexelizumab, Picoplatin, Pimecrolimus, Posaconazole, Pregabalin, PRO-1762, Progesterone caproate, Prulifloxacin; Ramelteon, Ranelic acid distrontium salt, Reparixin, Rosuvastatin calcium; Rotigotine; Satraplatin, Sertraline, Sipuleucel-T, SLIT-cisplatin, SNDX-275

  2. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, Ad5-FGF4, adeno-Interferon gamma, AE-941, AERx, alemtuzumab, alicaforsen sodium, almotriptan, alpharadin, anakinra, anatumomab mafenatox, ANG-453, anti-CTLA-4 Mab, AP-12009, aprepitant, aripiprazole, arsenic trioxide, astemizole, atlizumab, atomoxetine hydrochloride; Bevacizumab, BG-9928, BMS-188667, botulinum toxin type B, BufferGel; Caffeine, CDP-870, cetuximab, cilomilast, ciluprevir, clofarabine, continuous erythropoiesis receptor activator, CP-461; Darbepoetin alfa, deferasirox, desloratadine, desoxyepothilone B, diflomotecan, dolasetron, drotrecogin alfa (activated), duloxetine hydrochloride; ED-71, efalizumab, efaproxiral sodium, EKB-569, eletriptan, EMD-72000, enfuvirtide, erlotinib hydrochloride, escitalopram oxalate, etoricoxib; Fampridine, ferumoxytol, fondaparinux sodium; Gadofosveset sodium, gastrazole, gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride glutamine; hLM609, HSPPC-96, human insulin; IDD-1, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; Keratinocyte growth factor; Lapatinib, laquinimod, LDP-02, LE-SN38, levetiracetam, levosimendan, licofelone, liposomal doxorubicin, liposomal NDDP, lopinavir, lumiracoxib, LY-156735; Morphine hydrochloride, morphine-6-glucuronide, motexafin gadolinium, MS-27-275, MVA-5T4, MVA-Muc1-IL-2; Nemifitide ditriflutate, neridronic acid nitronaproxen, NSC-683864, NSC-703940, NVP-LAF-237; Oblimersen sodium, ocinaplon, oncomyc-NG, OPC-28326, ortataxel, ospemifene; Palonosetron hydrochloride, PEG-filgrastim peginterferon alfa-2(a), peginterferon alfa-2b, pegsunercept, pemetrexed disodium, pregabalin, prilocaine, pyridoxamine; RDP

  3. Determination of adenosine disodium triphosphate (ATP) using oxytetracycline-Eu 3+ as a fluorescence probe by spectrofluorimetry

    NASA Astrophysics Data System (ADS)

    Hou, Faju; Miao, Yanhong; Jiang, Chongqiu

    2005-10-01

    A new spectrofluorimetric method was developed for determination of adenosine disodium triphosphate (ATP). We studied the interactions between oxytetracycline (OTC)-Eu 3+ complex and adenosine disodium triphosphate (ATP) by using UV-vis absorption and fluorescence spectra. Using oxytetracycline (OTC)-Eu 3+ as a fluorescence probe, under the optimum conditions, ATP can remarkably enhance the fluorescence intensity of the OTC-Eu 3+ complex at λ = 612 nm and the enhanced fluorescence intensity of Eu 3+ ion is in proportion to the concentration of ATP. Optimum conditions for the determination of ATP were also investigated. The linear ranges for ATP are 8.00 × 10 -8-1.50 × 10 -6 mol L -1 with detection limits of 2.67 × 10 -9 mol L -1. This method is simple, practical and relatively free interference from coexisting substances and can be successfully applied to determination of ATP in samples. The mechanism of fluorescence enhancement between oxytetracycline (OTC)-Eu 3+ complex and ATP was also studied.

  4. IN VITRO PERCUTANEOUS ABSORPTION OF MONOSODIUM METHANERARSONATE (MSMA) AND DISODIUM METHANE-ARSONATE (DSMA) IN FEMALE B6C3F1 MICE

    EPA Science Inventory

    Percutaneous absorption of (14C] monosodium methanearsonate (MSMA) and disodium methanearsonate (DSMA) was investigated in female B6C3F1 mice from a variety of exposure conditions, including aqueous solution, solid compound, and soil. hese chemicals are the sodium salts of methan...

  5. [Treatment of multiple myeloma with high-dose chemotherapy and transplantation of autologous hematopoietic stem cells and subsequent maintenance therapy with interferon alfa-2b or interferon alfa 2b and dexamethasone. Report of the ongoing study of the "4W" Czech Myeloma Group].

    PubMed

    Adam, Z; Krejcí, M; Bacovský, J; Hejlová, N; Kuca, B; Svojgrová, M; Franková, H; Gumulec, J; Janca, J; Veprek, K; Januska, B; Lehanka, F; Rezek, Z; Praskac, P; Cahová, S; Vránová, M; Papajík, T; Králová, E; Novotná, J; Scudla, V; Koza, V; Drbal, J; Faber, E; Mareschová, I; Hájek, R

    1998-07-01

    We report our results with high-dose chemotherapy in previously untreated multiple myeloma patients (4 courses of VAD chemotherapy, collection of PBSC after priming with cyclophosphamide, 5 g/m2, high-dose chemotherapy with melphalan, 200 mg/m2). Second transplantation was indicated only for patients who did not achieve remission after the first high-dose therapy (paraprotein lower than 25% of the pretreatment value). For the second transplantation melphalan (200 mg/m2) with methylprednisolone (1.5 g for 5 days) were used as conditioning regimen. After high-dose therapy all patients were randomized into two arms of maintenance therapy: interferon alpha-2b or sequential maintenance therapy (interferon alpha-2b for 3 months followed after 4 week pause by 40 mg of dexamethasone days 1-4, 10-13 and 20-23. The administration of interferon alpha was resumed four weeks after the last dexamethasone for next three months. The maintenance therapy continued for 48 months or until the progression. Fifty-five patients were enrolled in the study from January 1996 to August 1997. Thirty-five patients have undergone the first transplantation and 57% of them reached complete remission. There were 10% of non-responders after the first high-dose regimen. The mean time to reach white blood cell count above 1 x 10(9)/L after the application of high dose melphalan and platelets more than 50 x 10(9)/L were 12.2 (range 6-16 days) and 12.4 (range 0-25 days), respectively. Grade 4 mucositis according to SWOG classification requiring total parenteral nutrition was presented in 40% of the patients. The mean number of 1 unit of platelets and 2 units of packed red blood cells transfusions were given within the posttransplant period. Early transplant related mortality was 3%. This paper describes the response and tolerance of each particular step of therapy. The follow-up has been too short to evaluate event-free and overall survivals. PMID:9748876

  6. Disodium hydrogen citrate sesquihydrate, Na2HC6H5O7(H2O)1.5

    PubMed Central

    Rammohan, Alagappa; Sarjeant, Amy A.; Kaduk, James A.

    2016-01-01

    The crystal structure of disodium hydrogen citrate sesquihydrate, 2Na2 +·C6H6O7 2−·1.5H2O, has been solved and refined using laboratory X-ray single-crystal diffraction data, and optimized using density functional techniques. The asymmetric unit contains two independent hydrogen citrate anions, four sodium cations and three water molecules. The coordination polyhedra of the cations (three with a coordination number of six, one with seven) share edges to form isolated 8-rings. The un-ionized terminal carb­oxy­lic acid groups form very strong hydrogen bonds to non-coordinating O atoms, with O⋯O distances of 2.46 Å. PMID:27555936

  7. Disodium hydrogen citrate sesquihydrate, Na2HC6H5O7(H2O)1.5.

    PubMed

    Rammohan, Alagappa; Sarjeant, Amy A; Kaduk, James A

    2016-07-01

    The crystal structure of disodium hydrogen citrate sesquihydrate, 2Na2 (+)·C6H6O7 (2-)·1.5H2O, has been solved and refined using laboratory X-ray single-crystal diffraction data, and optimized using density functional techniques. The asymmetric unit contains two independent hydrogen citrate anions, four sodium cations and three water molecules. The coordination polyhedra of the cations (three with a coordination number of six, one with seven) share edges to form isolated 8-rings. The un-ionized terminal carb-oxy-lic acid groups form very strong hydrogen bonds to non-coordinating O atoms, with O⋯O distances of 2.46 Å. PMID:27555936

  8. Oral disodium cromoglycate and ketotifen for a patient with eosinophilic gastroenteritis, food allergy and protein-losing enteropathy.

    PubMed

    Suzuki, Junzo; Kawasaki, Yukihiko; Nozawa, Ruriko; Isome, Masato; Suzuki, Shigeo; Takahashi, Ai; Suzuki, Hitoshi

    2003-09-01

    We present a case report of a 10 years old boy with protein-losing enteropathy and eosinophilic gastroenteritis who had positive histamine release tests, increased allergen-specific IgE antibodies to some food items, and low levels of total serum protein and albumin. Upper gastrointestinal endoscopy revealed a number of polyps and diffuse gastritis. Biopsy specimens of the stomach and duodenum showed widespread eosinophilia and neutrophilia. Although a restricted diet was recommended, a diet which excluded foods with positive results to both histamine release test and allergen-specific IgE antibodies was poorly tolerated, and the patient rejected systemic administration of corticosteroids. Thus, we initiated an oral disodium cromoglycate (DSCG) and ketotifen therapy. After oral DSCG and ketotifen administration, the patient's condition improved gradually. Therefore, oral DSCG and ketotifen therapy might be considered as treatment option in patients with eosinophilic gastroenteritis and protein-losing enteropathy caused by food allergy. PMID:15032404

  9. The effects of disodium cromoglycate on enhanced adherence of Haemophilus influenzae to A549 cells infected with respiratory syncytial virus.

    PubMed

    Fukasawa, Chie; Ishiwada, Naruhiko; Ogita, Junko; Hishiki, Haruka; Kohno, Yoichi

    2009-08-01

    Nontypeable Haemophilus influenzae (NTHi) secondary infection often complicates respiratory syncytial virus (RSV) infections. Previous studies have revealed that RSV infections enhance NTHi adherence to airway epithelial cells. In this study, we investigated the effects of disodium cromoglycate (DSCG) and corticosteroids, which are frequently used for the treatment of wheezing often related to RSV infections, on the adherence of NTHi to RSV-infected A549 cells. DSCG inhibited enhanced adherence of NTHi to RSV-infected A549 cells, whereas dexamethasone (Dex) and fluticasone propionate (Fp) did not. DSCG suppressed the expression of ICAM-1, which is one of the NTHi receptors. Furthermore, DSCG exhibited an inhibitory effect on RSV infections. It is suggested that DSCG exerts an anti-RSV effect, and consequently attenuates the expression of NTHi receptors. PMID:19390482

  10. Influence of Proton and Salt Concentration on the Chromonic Liquid Crystal Phase Diagram of Disodium Cromoglycate Solutions: Prospects and Limitations of a Host for DNA Nanostructures.

    PubMed

    Zhang, Bingru; Kitzerow, Heinz-S

    2016-03-31

    Lyotropic chromonic liquid crystals have recently been suggested for use as a self-organized host for dispersing and aligning self-organized DNA origami nanostructures. However, an appropriate pH value and a suitable cation concentration are necessary to stabilize such nanostructures and to avoid unfolding of the DNA. The present study shows that the nematic and columnar liquid crystal phases appearing in aqueous solutions of disodium cromoglycate are robust against the replacement of deionized water by a neutral or alkaline buffer solution. However, disodium cromoglycate precipitates when an acidic buffer is used or when the concentration of magnesium cations exceeds a critical concentration of about 0.6-0.7 mmol/L. PMID:26964003

  11. Effect of the Food Additives Sodium Citrate and Disodium Phosphate on Shiga Toxin-Producing Escherichia coli and Production of stx-Phages and Shiga toxin.

    PubMed

    Lenzi, Lucas J; Lucchesi, Paula M A; Medico, Lucía; Burgán, Julia; Krüger, Alejandra

    2016-01-01

    Induction and propagation of bacteriophages along the food production chain can represent a significant risk when bacteriophages carry genes for potent toxins. The aim of this study was to evaluate the effect of different compounds used in the food industry on the growth of Shiga toxin-producing Escherichia coli (STEC) and the production of stx-phage particles and Shiga toxin. We tested the in vitro effect of lactic acid, acetic acid, citric acid, disodium phosphate, and sodium citrate on STEC growth. A bacteriostatic effect was observed in most of treated cultures. The exceptions were those treated with sodium citrate and disodium phosphate in which similar growth curves to the untreated control were observed, but with reduced OD600 values. Evaluation of phage production by plaque-based assays showed that cultures treated with sodium citrate and disodium phosphate released phages in similar o lower levels than untreated cultures. However, semi-quantification of Stx revealed higher levels of extracellular Stx in STEC cultures treated with 2.5% sodium citrate than in untreated cultures. Our results reinforce the importance to evaluate if additives and other treatments used to decrease bacterial contamination in food induce stx-phage and Stx production. PMID:27446032

  12. Effect of the Food Additives Sodium Citrate and Disodium Phosphate on Shiga Toxin-Producing Escherichia coli and Production of stx-Phages and Shiga toxin

    PubMed Central

    Lenzi, Lucas J.; Lucchesi, Paula M. A.; Medico, Lucía; Burgán, Julia; Krüger, Alejandra

    2016-01-01

    Induction and propagation of bacteriophages along the food production chain can represent a significant risk when bacteriophages carry genes for potent toxins. The aim of this study was to evaluate the effect of different compounds used in the food industry on the growth of Shiga toxin-producing Escherichia coli (STEC) and the production of stx-phage particles and Shiga toxin. We tested the in vitro effect of lactic acid, acetic acid, citric acid, disodium phosphate, and sodium citrate on STEC growth. A bacteriostatic effect was observed in most of treated cultures. The exceptions were those treated with sodium citrate and disodium phosphate in which similar growth curves to the untreated control were observed, but with reduced OD600 values. Evaluation of phage production by plaque-based assays showed that cultures treated with sodium citrate and disodium phosphate released phages in similar o lower levels than untreated cultures. However, semi-quantification of Stx revealed higher levels of extracellular Stx in STEC cultures treated with 2.5% sodium citrate than in untreated cultures. Our results reinforce the importance to evaluate if additives and other treatments used to decrease bacterial contamination in food induce stx-phage and Stx production. PMID:27446032

  13. A Combination Strategy of Ceftriaxone, Sulbactam and Disodium Edetate for the Treatment of Multi-Drug Resistant (MDR) Septicaemia: A Retrospective, Observational Study in Indian Tertiary Care Hospital

    PubMed Central

    Jambulingappa, Kiran Lakkol

    2015-01-01

    Introduction Previous studies have suggested the use of rational combination therapy for the treatment of multi-drug resistant (MDR) infections. An antibiotic adjuvant entity (AAE) of ceftriaxone, sulbactam and disodium edetate (Elores) was approved for multi-drug resistant infections in India. Aim This study was designed to investigate the efficacy and safety of this AAE in patients with sepsis due to extended spectrum beta lactamse (ESBL) and metallo-beta lactamase (MBL) producing pathogens. Materials and Methods A retrospective observational study was conducted in patients admitted in intensive care unit (ICU) at tertiary health care site in India, with enrollment from 24 March, 2012 to 7 Aug, 2012. Patients eligible for enrollment had clear infection of bacterial septicaemia, were aged 12-65 years, and were considered for treatment with Cephalosporins categories of antibiotics. Results Total 18 patients were included in the study and all assigned to combination of ceftriaxone, sulbactam and disodium edetate. Complete clinical cure in terms of relief and no-disease symptoms had observed in 15 (83.3%) subjects, however 3 (16.6%) showed treatment failure (TF). Similarly for bacteriological eradication response, 15 (83.3%) patients displayed complete bacteriological eradication response and 03 (16.6%) subjects showed TF. No serious side effect was observed during the study. Conclusion This study recommends the use of combination of ceftriaxone, sulbactam and disodium edetate (EDTA) for the treatment of MDR septicaemia associated with ESBL and MBL producing microbes. PMID:26673348

  14. Activity of pemetrexed and high-dose gefitinib in an EGFR-mutated lung adenocarcinoma with brain and leptomeningeal metastasis after response to gefitinib

    PubMed Central

    2012-01-01

    About 20% to 40% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases during the natural course of their disease. The prognosis for such patients is very poor with limited survival. In addition to the standard whole brain radiation therapy (WBRT), some studies have shown that chemotherapy drugs and/or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) can improve the outcome of these patients. Here, we report a stage IIIA patient who developed multiple brain metastases one year after operation. Oral gefitinib with concurrent WBRT were given as first-line therapy. Complete response and a 50-month progression-free survival (PFS) were obtained. Double dosage of gefitinib (500 mg per day) together with pemetrexed were given as the second-line therapy after the patient developed new brain lesions and leptomeningeal metastasis during the maintenance therapy of gefitinib. The PFS for the second-line therapy was six months. In total, the patient obtained an overall survival of 59 months since the first diagnosis of brain metastases. Mutational analysis showed a 15-nucleotide deletion and a missense mutation in exon 19 of the EGFR gene, and a missense mutation at codon 12 of the K-ras gene. These underlying genetic changes might partially explain the long-term survival of this patient after brain metastases when treated with concurrent or sequential therapies of EGFR-TKI, radiotherapy and chemotherapy. PMID:23134665

  15. Spectroscopic study of the interaction between adenosine disodium triphosphate and gatifloxacin-Al3+ complex and its analytical application.

    PubMed

    Kamruzzaman, Mohammad; Faruqui, A Nayeem; Hossain, Mohammed Ifteker; Lee, Sang Hak

    2015-11-01

    A new and sensitive spectrofluorimetric method has been proposed to determine trace amount of adenosine disodium triphosphate (ATP). The method is based on the fluorimetric interaction between gatifloxacin (GFLX)-aluminium (III) (Al(3+) ) complex and ATP and studied using UV-visible and fluorescence spectroscopy. Weak luminescence spectra of Al(3+) were enhanced after complexation with GFLX at 423 nm upon excitation at 272 nm due to energy transfer from the ligand to the Al(3+) ion. It was observed that the FL emission spectrum of GFLX-Al(3+) was enhanced significantly by the addition of ATP. Under the optimal conditions, the enhancement of FL intensity at 423 nm was responded linearly with the concentration of ATP in the range 1.3 × 10(-10) - 1.0 × 10(-8) mol L(-1) with correlation coefficient (r) of 0.9981. The limit of detection (LOD) was found to be 1.1 × 10(-11) mol L(-1) for ATP with the standard deviation (RSD) of 1.21% for five repeated measurement of 2.3 × 10(-8) mol L(-1) ATP. The presented method is simple, sensitive, free from coexisting interferents and can be applied successfully to determine ATP in the real samples. PMID:25683636

  16. The novel bisphosphonate disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate increases bone mass in post-ovariectomy rats.

    PubMed

    Takizawa, Aiko; Chiba, Mirei; Ota, Takeru; Yasuda, Mayumi; Suzuki, Keiko; Kanemitsu, Takuya; Itoh, Takashi; Shinoda, Hisashi; Igarashi, Kaoru

    2016-05-01

    The novel bisphosphonate (BP) disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate (MPMBP) is a non-nitrogen-containing BP with an antioxidant side chain that possesses anti-inflammatory properties. We investigated the systemic effects of this compound on bone loss induced by ovariectomy (OVX) in adult rats. Micro-computed tomography revealed that MPMBP increased bone mass and density in both the metaphysis and diaphysis, and improved the structural properties important for mechanical strength of osteoporotic bone. Sequential bone labeling with tetracycline and calcein indicated that MPMBP decreased longitudinal growth of the primary spongiosa (PS), but stimulated cortical bone formation in the diaphysis. MPMBP increased type I collagen accumulation in the PS, and decreased the number and size of adipocytes in the bone marrow, suggesting inhibition of increased bone marrow adipogenesis induced by OVX. Furthermore, MPMBP reduced the number of bone resorbing cathepsin K-positive osteoclasts induced by OVX. These results suggest that MPMBP could improve bone loss induced by estrogen deficiency. Both stimulation of bone formation and inhibition of bone resorption might play a role in the increase in bone mass and bone density after MPMBP treatment. PMID:27245552

  17. Disodium octaborate tetrahydrate treatments to slash pine for protection against formosan subterranean termite and eastern subterranean termite (isoptera: rhinotermitidae)

    SciTech Connect

    Mauldin, J.K.; Kard, B.M.

    1996-06-01

    Minimum retentions of disodium octaborate tetrahydrate (DOT) needed in slash pine, Pinus elliottii Engelm. variety elliottii, wood to provide maximum protection against 2 species of subterranean termites were determined in choice and no-choice laboratory tests. Efficacy criteria for DOT were greater or equal to 90% termite mortality and equal to or less than 5% loss in weight of treated wooden blocks. For termites fed only DOT-treated wood, 0.10 and 0.30% boric acid equivalent (BAE, percentage of boric acid based on dry weight of wood, assuming all boron is present as boric acid) protected wood from the eastern subterranean termite, Reticulitermes flavipes (Kollar), and Formosan subterranean termite, Coptotermes formosanus Shiraki, respectively. When termites had a choice between treated or nontreated wooden blocks were not in contact with soil or exposed to rain, a BAE of 0.30% protected the wood from naturally occuring Reticulitermes sp. for 18 mo. In wooden structures under constant pressure from subterranean termites, concentrations greater than 0.54% BAE may be required to protect wood, especially against C. formosanus.

  18. Exploring the sodium storage mechanism in disodium terephthalate as anode for organic battery using density-functional theory calculations

    NASA Astrophysics Data System (ADS)

    Sk, Mahasin Alam; Manzhos, Sergei

    2016-08-01

    We present an ab initio study of sodium storage mechanism in disodium terephthalate (Na2TP) which is a very promising anode material for organic sodium (Na)-ion batteries with reported experimental capacities of ∼255 mAh g-1, previously attributed to Na attachment to the two carboxylate groups (coordinating to oxygen atoms). We show here that the inserted Na atoms prefer to bind at carboxylate sites at low Na concentrations and are dominant for insertion of up to one Na atom per molecule; for higher Na concentrations, the hexagonal sites (on the aromatic ring) become dominant. We confirm that the Na2TP crystal can store a maximum of two Na atoms per molecule, as observed in experiments. Our current results are intriguing as we reveal that the Na binding at carboxylate sites contributes to the initial part of Na2TP sodiation curve and the Na binding at hexagonal sites contributes to the second part of the curve. The inserted Na atoms donate electrons to empty states in the conduction band. Moreover, we show that the Na diffusion barriers in clean Na2TP can be as low as 0.23 eV. We also show that there is significant difference in the mechanism of Na interaction between individual molecules and the crystal.

  19. Transport of quercetin di-sodium salt in the human intestinal epithelial Caco-2 cell monolayer 139.

    PubMed

    Milane, H A; Al Ahmad, A; Naitchabane, M; Vandamme, T F; Jung, L; Ubeaud, G

    2007-01-01

    Quercetin di-sodium salt (QDS), a water-soluble derivative of quercetin (Q), is a potent free radical scavenger. The aim of this study was to examine the in vitro intestinal transport of QDS compared to that of Q using the Caco-2 human intestinal epithelial cell line. The apical (A) to basolateral (B) transport of QDS was found to be higher than the B to A transport of this compound. This polarized transport involved the presence of a carrier protein system. The involvement of the sodium/glucose transporter-1 (SGLT-1) was shown by using phloridzin, a selective inhibitor of this conveyor system. However, the transport of Q was not affected by this inhibitor. Moreover, the influx of QDS was pH-sensitive and decreased at pH 5.5 compared with that observed at pH 7.4 and 6.5. The permeability of QDS was 10-fold higher than that of Q. This could be explained by the involvement of SLGT-1 and the absence of an active efflux pump in the absorption of QDS in comparison with Q. This finding was supported by comparing the solubility of Q with that of QDS. This study indicates that both the higher solubility of QDS and its dependence on the SGLT-1 transport system resulted in more efficient permeability compared to Q. PMID:18062406

  20. Influence of salt additives on phase transformation of guanosine 5-monophosphate disodium in anti-solvent crystallization

    NASA Astrophysics Data System (ADS)

    Nguyen, Anh-Tuan; Kang, Jeongki; Kim, Woo-Sik

    2013-06-01

    The influence of sodium chloride (NaCl) as an additive on the anti-solvent crystallization of guanosine 5-monophosphate disodium (GMP-2Na) was investigated in continuous Couette-Taylor (CT) and batch mixing tank (MT) crystallizers. The anti-solvent crystallization initially precipitated amorphous solids of GMP-2Na, which then slowly transformed into hydrate crystals in the solution. However, the phase transformation of GMP-2Na was markedly promoted by the sodium chloride additive due to the common ion effect. While the normal phase transformation in the batch MT crystallizer required over 120 min of crystallization time without using the sodium chloride additive, the process was completed within 60 min when a small amount of the salt additive was added. The phase transformation was also significantly accelerated in the continuous CT crystallizer. Without using the sodium chloride additive, 7 min of the mean residence time was required for the production of 100% hydrate GMP crystals. However, when using the sodium chloride additive, a mean residence time of only 2 min was sufficient to completely transform the amorphous solids of GMP-2Na into hydrate crystals due to the common ion effect combined with the effective fluid motion of the Taylor vortex for the mass transfer.

  1. Long-term Study of Disodium Cromoglycate in Treatment of Severe Extrinsic or Intrinsic Bronchial Asthma in Adults

    PubMed Central

    1972-01-01

    The results are reported here of a long-term double-blind controlled clinical trial of disodium cromoglycate (D.S.C.G.) and isoprenaline, D.S.C.G. alone, isoprenaline alone, and a placebo given as a powder for inhalation in the treatment of severe bronchial asthma. At the end of one year 16 out of 20 patients on D.S.C.G.-isoprenaline remained on the allocated capsules, compared with 10 out of 15 on D.S.C.G., 5 out of 20 on isoprenaline, and 3 out of 19 taking the placebo. The differences between each of the D.S.C.G.-isoprenaline and D.S.C.G. regimens compared with the isoprenaline and placebo regimens were statistically significant. After eight weeks on four capsules a day the patients in each group were allocated at random so that half continued on full dosage and half on a reducing regimen. At the end of the year there was no significant difference in the failure rate between patients allocated the full dosage and the patients on the reducing dosage. The capsules were well tolerated and toxicity to D.S.C.G. was not observed. PMID:4629183

  2. Disodium Cromoglycate Reverses Colonic Visceral Hypersensitivity and Influences Colonic Ion Transport in a Stress-Sensitive Rat Strain

    PubMed Central

    Carroll, Siobhan Yvonne; O’Mahony, Siobhain Mary; Grenham, Susan; Cryan, John Francis; Hyland, Niall Patrick

    2013-01-01

    The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders. PMID:24367692

  3. Disodium cromoglycate reverses colonic visceral hypersensitivity and influences colonic ion transport in a stress-sensitive rat strain.

    PubMed

    Carroll, Siobhan Yvonne; O'Mahony, Siobhain Mary; Grenham, Susan; Cryan, John Francis; Hyland, Niall Patrick

    2013-01-01

    The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders. PMID:24367692

  4. NCCTG N0821 (Alliance): A phase II first-line study of pemetrexed, carboplatin and bevacizumab in elderly patients with advanced nonsquamous non-small cell lung cancer with good performance status

    PubMed Central

    Dy, Grace K.; Molina, Julian R.; Qi, Yingwei; Ansari, Rafat; Thomas, Sachdev; Ross, Helen J.; Soori, Gamini; Anderson, Daniel; Aubry, Marie Christine; Meyers, Jeffrey; Adjei, Araba A.; Mandrekar, Sumithra; Adjei, Alex A.

    2014-01-01

    PURPOSE We hypothesized that the combination of bevacizumab, carboplatin and pemetrexed will be an effective first-line regimen in fit, elderly patients with nonsquamous NSCLC. PATIENTS AND METHODS Treatment-naïve, stage IIIB/IV nonsquamous NSCLC patients ≥ 70 years old with good performance status (ECOG PS 0-1) and adequate organ function were eligible. Carboplatin AUC 6, pemetrexed 500 mg/m2 and bevacizumab 15 mg/kg were administered on day 1 of each 21-day cycle (up to 6 cycles) followed by maintenance pemetrexed and bevacizumab. The primary endpoint of 6-month progression-free survival rate (PFS6) of at least 70% was assessed using a one-stage binomial design. Quality of life (QOL) questionnaires were administered. Polymorphisms in genes encoding relevant proteins (drug targets, transport and metabolism proteins) were correlated with treatment outcome. RESULTS Fifty-seven eligible patients were enrolled. Median age was 74.5 years. Median treatment cycles received was 6. The most common grade 3 or higher non-hematologic adverse events were fatigue (26%) and hypertension (11%). 16% had grade 4 neutropenia and 6.5% had grade 4 thrombocytopenia. Three patients experienced grade 3/4 hemorrhagic events (one pulmonary, two gastrointestinal). Primary endpoint of PFS6 was 60% (95% CI: 45.9–73%). Median PFS was 7.0 months (95% CI: 5.9–10.1), median overall survival was 13.7 months (95% CI: 9.4–16.8). Polymorphic KDR and VEGFA variants correlated with survival and toxicity, respectively. There was no significant change in overall QOL scores over time. CONCLUSION This regimen is feasible and did not decrease the QOL in this study population. However, it did not meet the primary efficacy endpoint. PMID:25157767

  5. Randomized Phase II Study of Pemetrexed, Carboplatin, and Thoracic Radiation With or Without Cetuximab in Patients With Locally Advanced Unresectable Non–Small-Cell Lung Cancer: Cancer and Leukemia Group B Trial 30407

    PubMed Central

    Govindan, Ramaswamy; Bogart, Jeffrey; Stinchcombe, Thomas; Wang, Xiaofei; Hodgson, Lydia; Kratzke, Robert; Garst, Jennifer; Brotherton, Timothy; Vokes, Everett E.

    2011-01-01

    Purpose Cancer and Leukemia Group B conducted a randomized phase II trial to investigate two novel chemotherapy regimens in combination with concurrent thoracic radiation therapy (TRT). Patients and Methods Patients with unresectable stage III non–small-cell lung cancer (NSCLC) were randomly assigned to carboplatin (area under the curve, 5) and pemetrexed (500 mg/m2) every 21 days for four cycles and TRT (70 Gy; arm A) or the same treatment with cetuximab administered concurrent only with TRT (arm B). Patients in both arms received up to four cycles of pemetrexed as consolidation therapy. The primary end point was the 18-month overall survival (OS) rate; if the 18-month OS rate was ≥ 55%, the regimen(s) would be considered for further study. Results Of the 101 eligible patients enrolled (48 in arm A and 53 in arm B), 60% were male; the median age was 66 years (range, 32 to 81 years); 44% and 35% had adenocarcinoma and squamous carcinoma, respectively; and more patients enrolled onto arm A compared with arm B had a performance status of 0 (58% v 34%, respectively; P = .04). The 18-month OS rate was 58% (95% CI, 46% to 74%) in arm A and 54% (95% CI, 42% to 70%) in arm B. No significant difference in OS between patients with squamous and nonsquamous NSCLC was observed (P = .667). The toxicities observed were consistent with toxicities associated with concurrent chemoradiotherapy. Conclusion The combination of pemetrexed, carboplatin, and TRT met the prespecified criteria for further evaluation. This regimen should be studied further in patients with locally advanced unresectable nonsquamous NSCLC. PMID:21747084

  6. Dry powder aerosols generated by standardized entrainment tubes from drug blends with lactose monohydrate: 1. Albuterol sulfate and disodium cromoglycate.

    PubMed

    Xu, Zhen; Mansour, Heidi M; Mulder, Tako; McLean, Richard; Langridge, John; Hickey, Anthony J

    2010-08-01

    The major objective of this study was: discriminatory assessment of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs. Drug/lactose interactive physical mixtures (2%w/w) were prepared. Their properties were measured: solid-state characterization of phase behavior and molecular interactions by differential scanning calorimetry and X-ray powder diffraction; particle morphology and size by scanning electron microscopy and laser diffraction; aerosol generation by SETs and characterization by twin-stage liquid impinger and Andersen cascade impactor operated at 60 L/min. The fine particle fraction (FPF) was correlated with SET shear stress (tau(s)), using a novel powder aerosol deaggregation equation (PADE). Drug particles were <5 microm in volume diameter with narrow unimodal distribution (Span <1). The lowest shear SET (tau(s) = 0.624 N/m(2)) gave a higher emitted dose (ED approximately 84-93%) and lower FPF (FPF(6.4) approximately 7-25%). In contrast, the highest shear SET (tau(s) = 13.143 N/m(2)) gave a lower ED (ED approximately 75-89%) and higher FPF (FPF(6.4) approximately 15-46%). The performance of disodium cromoglycate was superior to albuterol sulfate at given tau(s), as was milled with respect to sieved lactose monohydrate. Excellent correlation was observed (R(2) approximately 0.9804-0.9998) when pulmonary drug particle release from the surface of lactose carriers was interpreted by PADE linear regression for dry powder formulation evaluation and performance prediction. PMID:20198688

  7. Effects of dietary pyrroloquinoline quinone disodium on growth performance, carcass yield and antioxidant status of broiler chicks.

    PubMed

    Samuel, K G; Zhang, H J; Wang, J; Wu, S G; Yue, H Y; Sun, L L; Qi, G H

    2015-03-01

    Pyrroloquinoline quinone (PQQ), a putative essential nutrient and redox modulator in microorganisms, cell and animal models, has been recognized as a growth promoter in rodents. Growth performance, carcass yield and antioxidant status were evaluated on broiler chickens fed different levels of PQQ disodium (PQQ.Na2). A total of 784 day-old male Arbor Acres (AA) broilers were randomly allotted into seven dietary groups: negative control group (NC) fed a basal diet without virginiamycin (VIR) or PQQ.Na2; a positive control group (PC) fed a diet with 15 mg of VIR/kg diet; and PQQ.Na2 groups fed with 0.05, 0.10, 0.20, 0.40 or 0.80 mg PQQ.Na2/kg diet. Each treatment contained eight replicates with 14 birds each. The feeding trial lasted for 6 weeks. The results showed that chicks fed 0.2 mg PQQ.Na2/kg diet significantly improved growth performance comparable to those in PC group, and the feed efficiency enhancement effects of dietary PQQ.Na2 was more apparent in grower phase. Dietary addition of PQQ.Na2 had the potential to stimulate immune organs development, and low level dietary addition (<0.1 mg/kg) increased plasma lysozyme level. Broilers fed 0.2 mg PQQ.Na2/kg diet gained more carcasses at day 42, and had lower lipid peroxide malondialdehyde content and higher total antioxidant power in plasma. The results indicated that dietary PQQ.Na2 (0.2 mg/kg diet) had the potential to act as a growth promoter comparable to antibiotic in broiler chicks. PMID:25229409

  8. Tolerability and pharmacokinetics of disodium folinate following single intravenous doses in healthy Chinese subjects: an open-label, randomized, single-center study.

    PubMed

    Liu, Yani; Zhou, Jiali; Li, Zhongfang; Yang, Chunxiao; Wu, Jianhong; Zhang, Yu; Shi, Shaojun; Li, Yunqiao

    2015-12-01

    The tolerability and pharmacokinetics of disodium folinate may vary with different races, and these variations might result in different outcomes. This study assessed the tolerability and pharmacokinetics of disodium folinate following single intravenous doses in healthy Chinese subjects, with gender factor also taken into account. Subjects were randomized to receive a single dose of disodium folinate at 20, 200, or 300 mg/m(2) administered intravenously over a time period of 10 min. Sequential blood samples were collected at regular intervals over 24 h after dosing and were analyzed using a validated high-performance liquid chromatography (HPLC) method. Pharmacokinetic parameters, including C max, AUC0-t, t 1/2, V d, and CL, were calculated using non-compartmental models. Tolerability was assessed by collecting adverse events (AEs) and monitoring vital signs, physical examinations, laboratory tests, and electrocardiograms. Following a single intravenous administration of disodium folinate 20, 200, and 300 mg/m(2), the mean (standard deviation) pharmacokinetic parameters were as follows: C max = 5.18 (0.58), 47.80 (10.10), and 69.93 (9.72) µg/mL; AUC0-t = 25.85 (3.36), 194.53 (30.18), and 355.26 (35.31) µg h/mL; AUC0-∞ = 30.24 (6.19), 215.43 (27.34), and 417.88 (54.81) µg h/mL; t 1/2 = 8.77 (2.57), 7.64 (1.81), and 9.08 (1.64) h; CL = 1.12 (0.18), 1.55(0.25), and 0.78 (0.09) L/h; V d = 13.75 (2.61), 17.38 (6.44), and 10.05 (1.49) L, respectively. The mean C max, AUC0-t, and AUC0-∞ increased in a dose-proportional manner. No significant differences in pharmacokinetic parameters were noted by gender. The most common AEs reported were mild redness at the injection site and neurological symptoms (headache, dizziness, and fatigue). PMID:25173761

  9. Effects of dietary pyrroloquinoline quinone disodium on growth, carcass characteristics, redox status, and mitochondria metabolism in broilers.

    PubMed

    Wang, J; Zhang, H J; Samuel, K G; Long, C; Wu, S G; Yue, H Y; Sun, L L; Qi, G H

    2015-02-01

    The potential benefits of supplementing pyrroloquinoline quinone disodium (PQQ·Na2) in the diet of broiler chicks were explored. We first examined the effect of different levels of dietary PQQ·Na2 on growth performance, carcass characteristics, and plasma biochemical parameters (trial 1). A total of 490 1-day-old male Arbor Acres (AA) broiler chicks were randomly divided into 5 dietary groups supplemented with 0, 0.05, 0.1, 0.2, or 0.4 mg PQQ·Na2/kg feed. As the 0.2 mg/kg PQQ·Na2 supplement gave the best performance, we then investigated whether this level of PQQ·Na2 influenced the redox status of plasma samples and mitochondrial-related metabolism (trial 2). A total of 120 1-day-old male AA chicks were randomly divided into 2 groups supplemented with 0 or 0.2 mg PQQ·Na2/kg diet. In trial 1, birds fed a diet containing 0.2 mg PQQ·Na2/kg showed lower feed conversion ratio compared with those fed the control diet in the overall study (d 1 to 42, P=0.039). Breast muscle yield (d 42) increased quadratically in response to dietary PQQ·Na2 supplementation (P=0.021). Analysis of plasma biochemical parameters revealed that feeding broiler chicks with ≤0.4 mg/kg PQQ·Na2 did not cause adverse health effects. In trial 2, birds fed 0.2 mg/kg PQQ·Na2 again showed improved feed efficiency than the control birds in the grower and overall phases (P=0.038 and 0.016, respectively). In addition, dietary PQQ·Na2 supplementation resulted in a higher anti-oxidative capacity (P=0.001), lower redox potential (P=0.008), and higher hepatic citrate synthase activity (P=0.002). In contrast, no difference in hepatic mitochondrial DNA copy number was observed between the 2 experimental groups (P>0.1). These results indicate that PQQ·Na2 is a potentially effective feed additive for improving feed efficiency, stimulating breast muscle development, and maintaining redox status in broiler chicks. Enhancement of mitochondria efficiency, rather than modulating mitochondria numbers

  10. Reversible posterior leukoencephalopathy syndrome following combinatorial cisplatin and pemetrexed therapy for lung cancer in a normotensive patient: A case report and literature review

    PubMed Central

    XIE, CHANGQING; JONES, VOVANTI T.

    2016-01-01

    Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare neurological syndrome of the brain, causing symptoms such as headaches, seizures, altered mental status and visual disturbances. The condition is predominantly associated with hypertension, eclampsia, renal impairment, cytotoxic drugs, immunosuppressive agents and molecular targeted agents, but the precise underlying mechanism of RPLS is not fully understood. The present study describes the case of a 65-year-old female patient with stage IIA non-small cell lung cancer who received cisplatin/pemetrexed treatment at the Leo W. Jenkins Cancer Center. Following 3 cycles of this therapy, the patient was referred to the Emergency Department of Vidant Medical Center with an altered mental status, subsequently presenting with epileptic seizures, a fever and a headache. A neurological examination revealed generalized hyperreflexia and paraparesis, with extensor posturing of the bilateral lower extremities. The lumbar puncture and electroencephalography results were normal, but cranial computed tomography (CT) scans revealed attenuation abnormalities in the bilateral parietal region and the left occipital lobe, with suspected metastasis. Cranial T2-weighted magnetic resonance imaging (MRI) indicated bilateral regions of increased signal intensity in the occipital, temporal and periventricular white matter. The patient was treated with anticonvulsants, steroids and antihypertensive drugs, recovered gradually from the symptoms and regained full consciousness. However, the patient reported residual weakness, presenting with an Eastern Cooperative Oncology Group score of 3, reflective of an inability to independently perform daily activities and self-care. A brain MRI performed 10 days later demonstrated that the subcortical edema had partially subsided. The patient was discharged on day 15 post-admission. A follow-up cranial CT examination 1 month later indicated a partial resolution of the abnormalities. The

  11. Pemetrexed had significantly better clinical efficacy in patients with stage IV lung adenocarcinoma with susceptible EGFR mutations receiving platinum-based chemotherapy after developing resistance to the first-line gefitinib treatment

    PubMed Central

    Yang, Chih-Jen; Tsai, Ming-Ju; Hung, Jen-Yu; Liu, Ta-Chih; Chou, Shah-Hwa; Lee, Jui-Ying; Hsu, Jui-Sheng; Tsai, Ying-Ming; Huang, Ming-Shyan; Chong, Inn-Wen

    2016-01-01

    Background Increased evidences show that epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors such as gefitinib could prolong progression-free survival (PFS) compared with cytotoxic chemotherapy for metastatic lung nonsquamous cell carcinoma harboring susceptible EGFR mutation, and gefitinib was served as the first-line therapy. However, acquired resistance is inevitable, but the salvage therapies are still unclear. Patients and methods We designed a retrospective study of the salvage therapy and enrolled patients with stage IV lung adenocarcinoma who had mutated EGFR and developed an acquired resistance to the first-line gefitinib in two university-affiliated hospitals in Taiwan during June 2011 to December 2014. Age, sex, smoking history, EGFR gene mutation, performance statuses, response rate, PFS2 (the PFS in salvage therapy), and overall survival (OS2, the OS in salvage therapy) were recorded. Results Two hundred and nine patients with mutated EGFR and who took gefitinib as first-line therapy were identified in the period, and a total of 98 patients who had been treated with salvage therapy with cytotoxic chemotherapy or erlotinib were eligible for this study. The overall response rate of second salvage therapy is 13%, and none of them received erlotinib. Patients who received chemotherapy had a trend for better PFS2 than those who received erlotinib (4.3 months vs 3.0 months, P=0.1417) but not in OS. Furthermore, patients who received platinum-based doublet had a trend for better PFS2 and a significantly better OS2 than those who received chemotherapy without platinum (PFS2: 4.9 months vs 2.6 months, P=0.0584; OS2: 16.1 months vs 6.7 months, P=0.0007). Analyses of the patients receiving platinum-based doublet showed that patients receiving pemetrexed had a significantly better PFS2 (6.4 months vs 4.1 months, P=0.0083) and a trend for better OS2 than those without pemetrexed treatment. Conclusion Pemetrexed-based platinum chemotherapy may be the

  12. Noninvasive monitoring of the genetic evolution of EGFR-mutant non-small-cell lung cancer by analyzing circulating tumor DNA during combination chemotherapy with gefitinib and pemetrexed or S-1

    PubMed Central

    Nakahara, Yoshiro; Takagi, Yusuke; Hosomi, Yukio; Kagei, Akiko; Yamamoto, Tomohiro; Sawada, Takeshi; Yomota, Makiko; Okuma, Yusuke; Mikura, Shinichiro; Okamura, Tatsuru

    2016-01-01

    Background Repetitive genotyping is useful to assess the genetic evolution of non-small-cell lung cancer (NSCLC) during treatment, but the need for sampling by biopsy is a major obstacle. Digital polymerase chain reaction (PCR) is a promising procedure for the detection of mutant alleles in plasma of cancer patients. Methods This prospective study enrolled patients with NSCLC and known epidermal growth factor receptor (EGFR) mutations and who had experienced disease progression during ongoing EGFR-tyrosine kinase inhibitor (TKI) therapy. Eligible patients received daily gefitinib and either pemetrexed or S-1 every 3 weeks until disease progression or the development of unacceptable toxicity. Peripheral blood was collected before and after the combination therapy for digital PCR and hepatocyte growth factor measurement. Results From May 2012 to January 2014, nine patients with a median age of 67 (range 52–80) years were enrolled. Patterns of disease progression during adjacent EGFR-TKI therapy were acquired resistance, observed in seven patients, and primary resistance, observed in two patients. Known EGFR mutations were detected in plasma samples of six (67%) patients at study enrollment. Of these, T790M mutation was concurrently detected in three (50%) patients. Four patients underwent gefitinib plus pemetrexed therapy, and five patients underwent gefitinib and S-1 therapy. The median number of cycles delivered was five, and the median progression-free survival was 5.7 months. Efficacy outcomes did not differ between treatments. After the combination therapy, plasma T790M status changed to positive in two patients. Hepatocyte growth factor level did not significantly change through the combination therapy. Conclusion The usefulness of monitoring the genetic evolution of EGFR-driven tumors using noninvasive procedures was demonstrated. Since continuation of EGFR-TKI therapy with cytotoxic agents has an acceptable tolerability and a possibility of inducing T790M

  13. Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of the Efficacy and Safety of Apricoxib in Combination With Either Docetaxel or Pemetrexed in Patients With Biomarker-Selected Non–Small-Cell Lung Cancer

    PubMed Central

    Edelman, Martin J.; Tan, Ming T.; Fidler, Mary J.; Sanborn, Rachel E.; Otterson, Greg; Sequist, Lecia V.; Evans, Tracey L.; Schneider, Bryan J.; Keresztes, Roger; Rogers, John S.; de Mayolo, Jorge Antunez; Feliciano, Josephine; Yang, Yang; Medeiros, Michelle; Zaknoen, Sara L.

    2015-01-01

    Purpose Overexpression of COX-2 correlates with advanced stage and worse outcomes in non–small-cell lung cancer (NSCLC), possibly as a result of elevated levels of COX-2–dependent prostaglandin E2 (PGE2). Exploratory analyses of studies that used COX-2 inhibitors have demonstrated potentially superior outcome in patients in whom the urinary metabolite of PGE2 (PGE-M) is suppressed. We hypothesized that patients with disease defined by PGE-M suppression would benefit from the addition of apricoxib to second-line docetaxel or pemetrexed. Patients and Methods Patients with NSCLC who had disease progression after one line of platinum-based therapy, performance status of 0 to 2, and normal organ function were potentially eligible. Only patients with a ≥ 50% decrease in urinary PGE-M after 5 days of treatment with apricoxib could enroll. Docetaxel 75 mg/m2 or pemetrexed 500 mg/m2 once every 21 days per the investigator was administered with apricoxib or placebo 400 mg once per day. The primary end point was progression-free survival (PFS). Exploratory analysis was performed regarding baseline urinary PGE-M and outcomes. Results In all, 101 patients completed screening, and 72 of the 80 who demonstrated ≥ 50% suppression were randomly assigned to apricoxib or placebo. Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib versus placebo. The median PFS for the control arm was 97 days (95% CI, 52 to 193 days) versus 85 days (95% CI, 67 to 142 days) for the experimental arm (P = .91). Conclusion Apricoxib did not improve PFS, despite biomarker-driven patient selection. PMID:25452446

  14. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-09-01

    -2a, Peginterferon alfa-2b, Pemetrexed disodium, Perillyl alcohol, Perphenazine 4-aminobutyrate, PeviPRO/breast cancer, PF-03814735, PHA-739358, Pimecrolimus, Plitidepsin, Posaconazole, Prasterone, Prasugrel, Pregabalin, Prucalopride, PRX-08066; rAAV2-TNFR:Fc, Ranelic acid distrontium salt, Ranibizumab, rCD154-CLL, Retapamulin, RTS,S/SBAS2, rV-PSA-TRICOM/rF-PSA-TRICOM; SG-2000, Sinecatechins, Sirolimus-eluting stent, Sorafenib, SP-1640, Strontium malonate, Succinobucol, Sunitinib malate; Taxus, Teduglutide, Telavancin hydrochloride, Telbivudine, Telmisartan/hydrochlorothiazide, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tocilizumab; Ustekinumab; V-5 Immunitor, Voriconazole, Vorinostat; Xience V, XL-184, XL-647, XL-765; Y-39983, Zibotentan. PMID:18985183

  15. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2006-10-01

    -globulin, ivabradine hydrochloride, ixabepilone; LA-419, lacosamide, landiolol, lanthanum carbonate, lidocaine/prilocaine, liposomal cisplatin, lutropin alfa; Matuzumab, MBP(82-98), mecasermin, MGCD-0103, MMR-V, morphine hydrochloride, mycophenolic acid sodium salt; Natalizumab, NCX-4016, neridronic acid, nesiritide, nilotinib, NSC-330507; O6-benzylguanine, olanzapine/fluoxetine hydrochloride, omalizumab; Panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pemetrexed disodium, perospirone hydrochloride, pexelizumab, phorbol 12-myristate 13-acetate, pneumococcal 7-valent conjugate vaccine, posaconazole, pramiconazole, prasugrel, pregabalin, prilocaine; rAAV-GAD65, raclopride, rasagiline mesilate, retapamulin, rosuvastatin calcium, rotigotine, rufinamide; SarCNU, SB-743921, SHL-749, sirolimus-eluting stent, sitaxsentan sodium, sorafenib; TachoSil, tadalafil, talampanel, Taxus, tegaserod maleate, telithromycin, telmisartan/hydrochlorothiazide, temsirolimus, tenatoprazole, teriflunomide, tetrathiomolybdate, ticilimumab, timcodar dimesilate, tipifarnib, tirapazamine, TPI, tramiprosate, trifluridine/TPI, trimethoprim; Ularitide, Urocortin 2; Valdecoxib, valganciclovir hydrochloride, valproate magnesium, valspodar, vardenafil hydrochloride hydrate, vitespen, vofopitant hydrochloride, volociximab, vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, zotarolimus, zotarolimus-eluting stent. PMID:17136234

  16. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-06-01

    , Nemonoxacin, Norelgestromin/ethinyl estradiol; Oblimersen sodium, Ocriplasmin, Olmesartan medoxomil, Omacetaxine mepesuccinate; Paclitaxel-eluting stent, Pagoclone, Paliperidone, Panitumumab, Pazopanib hydrochloride, PCV7, Pegaptanib octasodium, Peginterferon alfa-2a, Peginterferon alfa-2b/ ribavirin, Pegvisomant, Pemetrexed disodium, Perifosine, Pimecrolimus, Pitavastatin calcium, Plerixafor hydrochloride, Plitidepsin, Posaconazole, Pregabalin, Progesterone capriate; Raltegravir potassium, Ramucirumab, Ranelic acid distrontium salt, Rasburicase, Recombinant Bet V1, Recombinant human insulin, rhFSH, Rolofylline, Romidepsin, Romiplostim, Rosuvastatin calcium; Sapacitabine, Sevelamer carbonate, Sinecatechins, Sirolimus-eluting stent, Sitagliptin phosphate monohydrate, SN-29244, Sorafenib, Sugammadex sodium, Sunitinib malate; Tadalafil, Tafenoquine, Talnetant, Tanezumab, Tapentadol hydrochloride, Tasocitinib citrate, Technosphere/Insulin, Telcagepant, Tenofovir disoproxil fumarate, Teriparatide, Ticagrelor, Tigecycline, Tiotropium bromide, Tipifarnib, Tocilizumab, TS-041; Ulipristal acetate, Urtoxazumab, Ustekinumab; Vandetanib, Varenicline tartrate, Vicriviroc, Voriconazole, Vorinostat, VRC-HIVADV014-00-VP, VRC-HIVDNA016-00-VP; Zoledronic acid monohydrate. PMID:20664824

  17. Crystal structure of disodium 2-amino-6-oxo-6,7-di­hydro-1H-purine-1,7-diide hepta­hydrate

    PubMed Central

    Gur, Dvir; Shimon, Linda J. W.

    2015-01-01

    In the title compound, disodium 2-amino-6-oxo-6,7-di­hydro-1H-purine-1,7-diide hepta­hydrate, 2Na+·C5H3N5O2−·7H2O, the structure is composed of alternating (100) layers of guanine mol­ecules and hydrated Na+ ions. Within the guanine layer, the mol­ecules are arranged in centrosymmetric pairs, with a partial overlap between the guanine rings. In this compound, guanine exists as the amino–keto tautomer from which deprotonation from N1 and N7 has occurred (purine numbering). There are no direct inter­actions between the Na+ cations and the guanine anions. Guanine mol­ecules are linked to neighboring water mol­ecules by O—H⋯N and O—H⋯O hydrogen bonds into a network structure. PMID:25844188

  18. Determination of calcium disodium ethylenediaminetetraacetate (E385) in marketed bottled legumes, artichokes and emulsified sauces by gas chromatography with mass spectrometric detection.

    PubMed

    Jiménez, Juan J

    2014-01-01

    An original method to determine the food additive calcium disodium ethylenediaminetetraacetate in bottled food is proposed. The method involves the solid-liquid extraction of a portion of the whole content of legume or artichoke bottles, or the dilution of sauce samples, with water followed by an evaporation step by heating. Finally, ethylenediaminetetraacetic acid is methylated and determined by GC. Recoveries obtained on spiked samples were acceptable (96-108%) with RSDs comprised from 4.3% to 10%. Results suggest that the determination of additive only in the liquid phase of legume or artichoke bottles is not suitable to know its total amount because the additive is distributed between the liquid and solid phases. The contribution of each step of the analytical method to the uncertainty of the measured concentration has been assessed by a "bottom-up" approach, including the heterogeneity of the sample which resulted to be very variable after studying twenty samples. PMID:24444909

  19. Features of the Photoalignment of Disodium Bis-[(4-Hydroxy-3-Carboxylate-6-Methyl)Phenylazo]-5,5'-Dioxobenzothiophene in Thin Films

    NASA Astrophysics Data System (ADS)

    Chaplanova, J. D.; Muravskii, A. A.; Agabekov, V. E.; Gracheva, E. A.; Mikulich, V. S.

    2015-05-01

    Thin films and multilayer thin-fi lm coatings based on the new dichroic azo dye disodium bis[(4-hydroxy-3-carboxylate-6-methyl)phenylazo]-5,5'-dioxobenzothiophene (FtF-1) were produced by the spin-coating method. The optical properties and morphology of the FtF-1 films depended on the formation conditions and used solvents. Reversible photo-induced dichroism was observed in films obtained by spin-coating of FtF-1 solutions in DMF and aqueous polyvinylpyrrolidone on quartz substrates upon irradiation with plane-polarized light (λ = 450 nm, I = 15 mW/cm2). The anisotropic properties of the FtF-1 films were caused by trans-cis-isomerization of the irradiated dye molecules.

  20. Study of the laxative properties of the disodium salt of the sulfuric diester of 3,3-bis-(4-hydroxyphenyl)-7-methyl-2-indolinone (DAN-603 in the rat.

    PubMed

    Moretó, M; Goñalons, E; Giráldez, A; Torralba, A

    1976-03-01

    The influence of DAN-603 (disodium salt of sulphuric diester of 3,3-bis-(4-hydroxyphenyl)-7-methyl-2-indolinone) on the propulsive motility of the rat digestive tract was studied by means of indicators (charcoal and pyrvinium pamoate) and radioactive tracers (133BaSO4). The results showed that DAN-603 increases selectively the colon motility without modifying the speed of gastric, intestinal (small intestine) and caecal emptying. PMID:1261595

  1. Photodynamic therapy of human skin tumors using topical application of 5-aminolevulinic acid, dimethylsulfoxide (DMSO), and edetic acid disodium salt (EDTA)

    NASA Astrophysics Data System (ADS)

    Orenstein, Arie; Kostenich, Gennady; Tsur, H.; Roitman, Leonid; Ehrenberg, Benjamin; Malik, Zvi

    1995-01-01

    The results of photodynamic therapy (PDT) in 48 patients bearing basal cell carcinoma (BCC) and 7 patients with squamous cell carcinoma (SCC) of the skin are described. Five- aminolevulinic acid (5-ALA) was applied topically in two formulations. The first formulation contained 20% of 5-ALA in a base cream, and the second formulation (5-ALA composite cream), contained an additional 2% of dimethylsulfoxide (DMSO) and 2% of edetic acid disodium salt (EDTA). The creams were left on the skin for 2 - 5 hours. Production of protoporphyrin (PP) was measured in situ by a laser-induced fluorescence (LIF) method. The results of fluorescence measurement clearly indicate that PP accumulation in tumors induced by the 5-ALA composite cream was markedly higher than that induced by the 5-ALA cream. The tumors were light-irradiated (600 - 720 nm) after 4 - 5 hours of cream applications, using the light delivery system Versa-Light by a light dose of 100 J/cm2. The clinically superficial BCC tumors were highly responsive to PDT; the overall result in BCC patients was an 85.4% complete response. Histological examination showed an initial edematous reaction, followed by necrosis and complete disappearance of the tumor. The superficial SCC tumors showed a 100% complete response after PDT. The ulcerated nodular SCC showed partial responses.

  2. The effect of vehicle on physical properties and aerosolisation behaviour of disodium cromoglycate microparticles spray dried alone or with L-leucine.

    PubMed

    Najafabadi, Abdolhossien Rouholamini; Gilani, Kambiz; Barghi, Mohammadali; Rafiee-Tehrani, Morteza

    2004-11-01

    The aim of this study was to improve the aerosolisation behaviour of disodium cromogycate (DSCG), using spray drying technique. The effect of vehicle on the drug particle properties was investigated. L-leucine was selected as a natural antiadherent amino acid to improve the deagglomeration of DSCG particles. Spray dried samples of DSCG alone or with L-leucine were prepared from water and ethanol under the same conditions. The powder properties of the samples were examined by laser diffraction, helium densitometer, X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. The in vitro deposition was determined, using an Andersen cascade impactor with a Spinhaler at a flow rate of 60 l/min. An amorphous form of the drug was obtained when water was used. However, crystal transformation of original DSCG in the presence of ethanol during spray drying resulted in production of elongated particles. These particles exhibited improved aerodynamic properties, compared to the amorphous and commercial materials. Significant differences in fine particle fraction were observed using the two vehicles. Co-spray drying of DSCG and L-leucine improved the deposition profiles of the drug. These results indicated that the change in crystal structure of DSCG during spray drying process was susceptible to the nature of the vehicle. A crystalline form of DSCG with good aerodynamic properties was achieved during spray drying process. In addition, the processing of DSCG with L-leucine in a single step using ethanol resulted in an improvement in dispersion properties of the drug particles. PMID:15488683

  3. Preoperative Estimation of Future Remnant Liver Function Following Portal Vein Embolization Using Relative Enhancement on Gadoxetic Acid Disodium-Enhanced Magnetic Resonance Imaging

    PubMed Central

    Matsushima, Shigeru; Inaba, Yoshitaka; Sano, Tsuyoshi; Yamaura, Hidekazu; Kato, Mina; Shimizu, Yasuhiro; Senda, Yoshiki; Ishiguchi, Tsuneo

    2015-01-01

    Objective To retrospectively evaluate relative enhancement (RE) in the hepatobiliary phase of gadoxetic acid disodium-enhanced magnetic resonance (MR) imaging as a preoperative estimation of future remnant liver (FRL) function in a patients who underwent portal vein embolization (PVE). Materials and Methods In 53 patients, the correlation between the indocyanine green clearance (ICG-K) and RE imaging was analyzed before hepatectomy (first analysis). Twenty-three of the 53 patients underwent PVE followed by a repeat RE imaging and ICG test before an extended hepatectomy and their results were further analyzed (second analysis). Whole liver function and FRL function were calculated on the MR imaging as follows: RE x total liver volume (RE Index) and FRL-RE x FRL volume (Rem RE Index), respectively. Regarding clinical outcome, posthepatectomy liver failure (PHLF) was evaluated in patients undergoing PVE. Results Indocyanine green clearance correlated with the RE Index (r = 0.365, p = 0.007), and ICG-K of FRL (ICG-Krem) strongly correlated with the Rem RE Index (r = 0.738, p < 0.001) in the first analysis. Both the ICG-Krem and the Rem RE Index were significantly correlated after PVE (r = 0.508, p = 0.013) at the second analysis. The rate of improvement of the Rem RE Index from before PVE to after PVE was significantly higher than that of ICG-Krem (p = 0.014). Patients with PHLF had a significantly lower Rem RE Index than patients without PHLF (p = 0.023). Conclusion Relative enhancement imaging can be used to estimate FRL function after PVE. PMID:25995681

  4. Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesis.

    PubMed

    Aiello, Rossana; Crupi, Rosalia; Leo, Antonio; Chimirri, Serafina; Rispoli, Vincenzo; Marra, Rosario; Citraro, Rita; Cuzzocrea, Salvatore; De Sarro, Giovambattista; Russo, Emilio

    2015-02-01

    One of the most peculiar characteristics of the stress response is the pronounced inter-individual and inter-strain variability both in behavioral and neurochemical outcomes. Several studies confirm that rodents belonging to the same or different strain and/or gender, when exposed to a stressor, may show behavioral and cognitive differences. We compared the effects of long-term betamethasone 21-phosphate disodium (BTM), a widely clinically used corticosteroid, on animal behavior and neurogenesis in CD1 and DBA/2 mice. BTM treatment, in CD1 mice, increased body weight gain and anxiety parameters while having pro-depressant effects. Furthermore, BTM significantly reduced neurogenesis in the dentate gyrus of the hippocampus. Finally, BTM treatment induced a significant impairment in memory and learning performance in the Morris water maze. At odds, BTM administration, in DBA/2 mice, caused a significant reduction in the body weight while not modifying anxiety parameters. In addition, both an increased synaptogenesis and neurogenesis were found. Similarly to CD1 mice, also in DBA/2 mice, memory and learning were impaired. Our data confirm that long-term exposure to corticosteroids can generate or aggravate psychiatric/neurologic disorders such as depression, anxiety, memory and learning. Our study did not reveal significant differences between corticosterone and BTM treatment in CD1 mice. In contrast, BTM treatment in mice with an anxious phenotype (DBA/2 mice) revealed some contrasting results indicating that genetic factors can influence corticosteroids dependent effects. Finally, our data further underline the need for a re-evaluation of neurogenesis role; the increased neurogenesis observed in DBA/2 mice and behavioral effects might be distinguished phenomena. PMID:25289489

  5. Electrochemical preparation of sodium dodecylsulfate doped over-oxidized polypyrrole/multi-walled carbon nanotube composite on glassy carbon electrode and its application on sensitive and selective determination of anticancer drug: pemetrexed.

    PubMed

    Karadas, Nurgul; Ozkan, Sibel A

    2014-02-01

    Electrochemical oxidation of pemetrexed (PMX) was studied on bare, carboxylic acid functionalized multi-walled carbon nanotubes and over-oxidized polypyrrole modified (oo-PPy/MWCNTs-COOH/GCE) glassy carbon electrodes by cyclic and adsorptive stripping differential pulse voltammetric techniques. The oo-PPy/MWCNTs-COOH/GCE is very sensitive to the oxidation of PMX. The results proved that the over-oxidation of the PPy film gave a negative charge density on porous layer that improved the adsorption for PMX. The effects of pH, concentrations of MWCNTs and monomer, the number of cycles for the electropolymerization and the scan rate for sensor preparation were optimized. The MWCNTs-COOH and oo-PPy based sensor showed an excellent recognition capacity toward PMX. The linear responses have been obtained in the range from 8.00 × 10(-7)M to 1.00 × 10(-4)M with 2.04 × 10(-7)M detection limit for the bare GCE and from 1.00 × 10(-8)M to 1.00 × 10(-7)M with 3.28 × 10(-9)M detection limit for the modified GCE. The oxidation of PMX was controlled by the adsorption process on both types of electrode surfaces. The proposed methods were compared with the literature on UV spectrophotometric assay, which was carried out at an absorption maximum of 225 nm. The proposed method and the designed sensors have been successfully applied for the determination of PMX in pharmaceuticals. PMID:24401411

  6. Dietary supplementation of pyrroloquinoline quinone disodium protects against oxidative stress and liver damage in laying hens fed an oxidized sunflower oil-added diet.

    PubMed

    Wang, J; Zhang, H J; Xu, L; Long, C; Samuel, K G; Yue, H Y; Sun, L L; Wu, S G; Qi, G H

    2016-07-01

    The protective effects of dietary pyrroloquinoline quinone disodium (PQQ.Na2) supplementation against oxidized sunflower oil-induced oxidative stress and liver injury in laying hens were examined. Three hundred and sixty 53-week-old Hy-Line Gray laying hens were randomly allocated into one of the five dietary treatments. The treatments included: (1) a diet containing 2% fresh sunflower oil; (2) a diet containing 2% thermally oxidized sunflower oil; (3) an oxidized sunflower oil diet with 100 mg/kg of added vitamin E; (4) an oxidized sunflower oil diet with 0.08 mg/kg of PQQ.Na2; and (5) an oxidized sunflower oil diet with 0.12 mg/kg of PQQ.Na2. Birds fed the oxidized sunflower oil diet showed a lower feed intake compared to birds fed the fresh oil diet or oxidized oil diet supplemented with vitamin E (P=0.009). Exposure to oxidized sunflower oil increased plasma malondialdehyde (P<0.001), hepatic reactive oxygen species (P<0.05) and carbonyl group levels (P<0.001), but decreased plasma glutathione levels (P=0.006) in laying hens. These unfavorable changes induced by the oxidized sunflower oil diet were modulated by dietary vitamin E or PQQ.Na2 supplementation to levels comparable to the fresh oil group. Dietary supplementation with PQQ.Na2 or vitamin E increased the activities of total superoxide dismutase and glutathione peroxidase in plasma and the liver, when compared with the oxidized sunflower oil group (P<0.05). PQQ.Na2 or vitamin E diminished the oxidized sunflower oil diet induced elevation of liver weight (P=0.026), liver to BW ratio (P=0.001) and plasma activities of alanine aminotransferase (P=0.001) and aspartate aminotransferase (P<0.001) and maintained these indices at the similar levels to the fresh oil diet. Furthermore, oxidized sunflower oil increased hepatic DNA tail length (P<0.05) and tail moment (P<0.05) compared with the fresh oil group. Dietary supplementation of PQQ.Na2 or vitamin E decreased the oxidized oil diet induced DNA tail length

  7. Effect of Mineral Trioxide Aggregate, Calcium-Enriched Mixture Cement and Mineral Trioxide Aggregate with Disodium Hydrogen Phosphate on BMP-2 Production

    PubMed Central

    Ghasemi, Negin; Rahimi, Saeed; Lotfi, Mehrdad; Solaimanirad, Jafar; Shahi, Shahriar; Shafaie, Hajar; Salem Milani, Amin; Shakuie, Sahar; Zand, Vahid; Abdolrahimi, Majid

    2014-01-01

    Introduction: One of the hypotheses regarding the calcification induction by mineral trioxide aggregate (MTA) is the involvement of transforming growth factor-Beta (TGF-β) super family. Calcium-enriched mixture (CEM) cement is one of the endodontic biomaterials with clinical applications similar to MTA. The aim of the present in vitro study was to compare the induction of bone morphogenic protein-2 (BMP-2) by a combination of disodium hydrogen phosphate (DSHP) and tooth colored ProRoot MTA (WMTA), to that of CEM cement and WMTA. Methods and Materials: Human gingival fibroblasts (HGFs) were obtained from the attached gingiva of human premolars. HGFs were cultured in Dulbecco’s Modified Eagle’s medium, supplemented with 10% fetal calf serum, penicillin, and streptomycin. Cells in groups 1, 2 and 3 were exposed to WMTA, CEM and WMTA+DSHP discs, respectively. The fourth group served as the control. After 72 h of exposure, HGF viability was determined by Mosmann’s tetrazolium toxicity (MTT) assay. BMP-2 levels in cell-free culture media were determined by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using the one-way ANOVA, followed by the post hoc Games-Howell test for BMP-2 and post hoc Tukey’s test for the results of MTT assay. Results: Cellular viability was significantly higher in group 3 compared to the other groups (P<0.05); however, CEM and WMTA did not exhibit significant differences (P=0.08). The control group exhibited significantly higher cellular viability in comparison to the other groups of the study (P<0.05). The highest and lowest protein production rates were observed in the WMTA (3167±274.46 pg/mL) and WMTA+DSHP (1796±839.49 pg/mL) groups, respectively. There were no significant differences between the control, WMTA and CEM groups (P>0.05). Conclusion: WMTA and CEM did not exhibit any significant differences in terms of inducing BMP-2 production; however, incorporation of DSHP into WMTA resulted in a

  8. Cost effectiveness of first-line pemetrexed plus platinum compared with other regimens in the treatment of patients with nonsquamous non-small cell lung cancer in the US outpatient setting.

    PubMed

    Shah, Manan; Winfree, Katherine B; Peterson, Patrick; Gruschkus, Stephen K; Eaddy, Michael; Green, Mark R

    2013-10-01

    This retrospective observational study evaluated cost effectiveness of first-line treatment of advanced nonsquamous non-small cell lung cancer (NSCLC) with pemetrexed/platinum (Pem/Plat) relative to paclitaxel/carboplatin (Pac/Carbo) and paclitaxel/carboplatin/bevacizumab (Pac/Carbo/Bev). Patients initiating first-line treatment from 2006 to 2009 were identified in electronic medical records of 20 US oncology practices. Pem/Plat patients were matched 1:1 on important characteristics with Pac/Carbo and Pac/Carbo/Bev patients and followed for 1 year to assess progression, survival, and costs. Bootstrapping was used to calculate the probability of falling within quadrants of the incremental cost-effectiveness plane. Kaplan-Meier analysis and Cox proportional hazards regression modeling were also performed. Three hundred Pem/Plat patients (mean age, 67.6 years; male, 56.0%; PS 0/1, 71.0%) were matched with 300 patients in the other cohorts. Median PFS was 134 days (Pem/Plat) versus 106 days (Pac/Carbo) (hazard ratio [HR]: 0.67, P < 0.001) and 126 days (Pac/Carbo/Bev) (HR: 0.68, P < 0.001). Median OS was 298 days (Pem/Plat) versus 218 days (Pac/Carbo) (HR: 0.88, P = 0.08) and 271 days (Pac/Carbo/Bev) (HR: 0.93, P = 0.31). Pem/Plat therapy costs were higher versus Pac/Carbo ($21,841 higher PFS; $19,137 higher OS; P ≤ 0.05) and lower versus Pac/Carbo/Bev ($15,160 lower PFS; $19,946 lower OS; P ≤ 0.05). Pem/Plat had a greater probability of higher costs/higher effectiveness versus Pac/Carbo (PFS, 90.1%; OS, 96.3%) and lower costs/higher effectiveness versus Pac/Carbo/Bev (PFS, 69.5%; OS, 85.0%). Pem/Plat had higher cost and effectiveness than Pac/Carbo; depending on a payer's or society's willingness to pay, Pem/Plat may be considered cost effective compared with Pac/Carbo. Pem/Plat yielded greater effectiveness with lower costs than Pac/Carbo/Bev. PMID:23973203

  9. A redetermination of the structure of poly[[μ4-(R)-2-ammonio-3-sulfonato­propano­ato]aqua­sodium], originally reported as poly[[μ7-l-cysteato(2−)]disodium

    PubMed Central

    Brown, I. David

    2012-01-01

    The structure originally reported as poly[[μ7-l-cysteato(2−)]disodium], [Na2(C3H5NO5S)]n [Liu (2002). Acta Cryst. E67, m1346–m1347], has been redetermined with one of the sodium atoms replaced with a water mol­ecule and an additional proton attached to the amine group, resulting in the revised formula [Na{CO2CH(CH2SO3)NH3}(H2O)]n. The agreement index, wR, has been reduced from 0.159 to 0.087 and the global instability index from 0.56 vu (valence units) to the acceptable value of 0.11 vu. PMID:22606082

  10. Toxicology and Carcinogenesis Studies of 4,4'-Diamino-2,2'-Stilbenedisulfonic Acid Disodium Salt (CAS No. 7336-20-1) in F344 Rats and B6C3F1 Mice (Feed Studies).

    PubMed

    1992-08-01

    4,4'-Diamino-2,2'-stilbenedisulfonic acid, disodium salt, is used in the synthesis of dyes and optical brighteners or fluorescent whitening agents. Toxicology and carcinogenesis studies were conducted by administering the chemical (approximately 14% water, 6% sodium chloride, 4% impurities, and 76% 4,4'-diamino-2,2'-stilbenedisulfonic acid) in feed to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Chinese hamster ovary cells. 14-Day Studies: Groups of five rats and five mice of each sex were given 0, 6,250, 12,500, 25,000, 50,000, or 100,000 ppm 4,4'-diamino-2,2'-stilbenedisulfonic acid, disodium salt, in feed for 14 days. All rats and mice survived to the end of the studies. The mean body weight gain of male rats receiving 50,000 or 100,000 ppm and of female rats and male and female mice receiving 100,000 ppm was significantly lower than those of the respective controls. Clinical findings included diarrhea in the rats and mice receiving 100,000 ppm. There were no chemical-related changes in absolute or relative organ weights in rats or mice. There were no gross or microscopic lesions related to chemical administration in rats or mice. 13-Week Studies: Groups of 10 rats and 10 mice of each sex were given 0, 6,250, 12,500, 25,000, 50,000, or 100,000 ppm 4,4'-diamino-2,2'-stilbenedisulfonic acid, disodium salt, in feed for 13 weeks. One female rat, six male mice, and one female mouse in the 100,000 ppm dose groups died during the studies. Mean body weight gain was significantly decreased in male rats and female mice receiving 50,000 or 100,000 ppm, in male mice receiving 25,000, 50,000, or 100,000 ppm, and in female rats receiving 100,000 ppm. Clinical findings in rats that received 50,000 or 100,000 ppm and in mice that received 100,000 ppm included diarrhea, emaciation, and hyperemia of the perineum. There were no biologically significant changes in

  11. Determination of barium, strontium and nine minor and trace elements in impure barite and strontianite by inductively-coupled plasma atomic-emission spectrometry after dissolution in disodium ethylenediaminetetraacetate.

    PubMed

    Gupta, J G

    1991-10-01

    A new method has been developed for the determination of barium, strontium, silicon and nine minor and trace elements of barite and strontianite associated with gangue materials. It involves dissolution of the sample by boiling under reflux with a concentrated solution of disodium ethylenedi-aminetetraacetate (EDTA-2Na) in the presence of ammonium hydroxide. Barite and strontianite dissolve quantitatively under this condition, and any associated silicate and sulphide mineral impurities, remaining insoluble, are filtered off and ignited to constant weight in a platinum crucible. Silica is determined gravimetrically by heating the residue with concentrated sulphuric and hydrofluoric acids, followed by ignition to oxides. The residue is fused with sodium bisulphate and dissolved in dilute sulphuric acid. After suitable dilution of the EDTA-2Na solution, Ba, Sr, Be, Co, Cr, Cu, La, Ni, V, Yb and Zn are determined by inductively-coupled plasma atomic-emission spectrometry (ICP-AES). The bisulphate fusion product is separately analysed by ICP-AES, and the elements found are combined with those obtained from the EDTA-2Na solution. The replicate values of this work compare well with each other and with other values obtained by independent methods. PMID:18965264

  12. Anti-allergic and anti-inflammatory properties of a potent histamine H1 receptor antagonist, desloratadine citrate disodium injection, and its anti-inflammatory mechanism on EA.hy926 endothelial cells.

    PubMed

    Jie, Qiong; Kodithuwakku, Nandani Darshika; Yuan, Xin; He, Guangwei; Chen, Meiling; Xu, Shuhong; Wu, Yulin

    2015-05-01

    The present study, demonstrates that, desloratadine citrate disodium injection (DLC) possesses antihistaminic, anti-allergic and anti-inflammatory properties and elucidates its molecular mechanisms of anti-inflammatory properties. In vitro antihistamine activity of DLC was determined in guinea pig isolated tissues. In vivo antihistamine effects were evaluated after following intravenous administration of DLC in mice with histamine- induced paw edema and in rats with increased capillary permeability. Anti-allergic effects were assessed through passive cutaneous anaphylactic (PCA) reactions in sensitized rodents and ovalbumin-induced allergic rhinitis in rats. Anti-inflammatory properties and molecular mechanisms of DLC were determined on histamine- and lipopolysaccharide (LPS)-induced EA.hy926 endothelial cells. DLC exhibited significant and reversible inhibition of histamine-induced contractions of isolated guinea pig ileum with pA2 value of 8.88. Histamine-induced paw edema and increased capillary permeability were notably inhibited by DLC intravenous administration. In the model of PCA reactions, DLC showed significant activity in a dose-dependent nd potently inhibited both the early-phase and late-phase allergic reaction of ovalbumin-induced allergic rhinitis in rats. DLC alleviated the rhinitis symptoms and inhibited inflammatory cell infiltration, IL-4 and protein leakage in nasal lavage fluid (NLF). In EA.hy926 cells, DLC significantly inhibited the histamine- and LPS- induced IL-6 and IL-8 production and P-selectin and intercellular cell adhesion molecule-1 (ICAM-1) expression. Moreover, DLC reduced translocation of nuclear factor-kappaB (NF-κB) to the nucleus in activated EA.hy926 cells. These results provide evidence that DLC possesses potent antihistaminic, anti-allergic and, anti-inflammatory properties via suppressing IL-6, IL-8, P-selectin and ICAM-1 expression. PMID:25704613

  13. The effect of disodium cromoglycate, budesonide, and cyclosporin A on interleukin-4, interleukin-5, and interleukin-13 secretions in Der p I-stimulated T cells from house dust mite-sensitive atopic and nonatopic individuals.

    PubMed

    Oh, Jae-Won; Lee, Ha-Baik; Chung, Yong-Hoon; Choi, Yong

    2002-01-01

    Disodium cromoglycate (DSCG), budesonide, and cyclosporin A (CsA) were the well-known immunomodulators for the allergic and immunologic diseases clinically. In this study, we evaluated the characteristics of inhibition on cytokine synthesis of Der p I-stimulated T cells by the same inhibiting concentrations of DSCG, budesonide, and CsA in house-dust mite antigen (Der p I)-specific atopic and nonatopic healthy individuals. Seven house dust mite allergen specific patients were recruited for this study. Seven healthy volunteers were included on the basis of negative allergic manifestations and low serum immunoglobulin E values. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence of recombinant interleukin (rIL)-2 with or without budesonide, DSCG, CsA, and Der p I for 48 hours. Cells were stained with anti-CD4 fluorescein isothiocyanate-conjugated monoclonal antibody, and then anti-human IL-4 phycoerythrin, IL-5, or IL-13 monoclonal antibody, respectively, was added to both blocked and stained samples. Incubation of PBMC from atopics with each immunomodulator and Der p I resulted in the reduction of IL-4 secretion compared with Der p I alone stimulation. However, IL-4 secretion in PBMC from nonatopics was not reduced with DSCG and Der p I stimulation. IL-4, IL-5, and IL-13 secretions of PBMC from atopics were significantly decreased after incubation with each immunomodulator and Der p I, compared with after incubation with Der p I alone. These results might be considered to show either that DSCG has a selective inhibiting effect on cytokine production in T cells from atopics or is a weak inhibitor of cytokine secretions compared with budesonide and CsA at even strength for the inhibition of lymphocyte proliferation in normal, healthy individuals. PMID:12001789

  14. Combined Application of Gadoxetic Acid Disodium-Enhanced Magnetic Resonance Imaging (MRI) and Diffusion-Weighted Imaging (DWI) in the Diagnosis of Chronic Liver Disease-Induced Hepatocellular Carcinoma: A Meta-Analysis

    PubMed Central

    Li, Xiang; Li, Chenxia; Wang, Rong; Ren, Juan

    2015-01-01

    Objective Gadoxetic acid disodium (Gd-EOB-DTPA) is a magnetic resonance imaging (MRI) contrast agent to target the liver cells with normal function. In clinical practice, the Gd-EOB-DTPA produces high quality hepatocyte specific image 20 minutes after intravenous injection, so DWI sequence is often performed after the conventional dynamic scanning. However, there are still some disputes about whether DWI sequence will provide more effective diagnostic information in clinical practice. This study aimed to explore the diagnostic value of combining Gd-EOB-DTPA-enhanced MRI and DWI in the detection of hepatocellular carcinoma (HCC) in patients with chronic liver disease. Methods A systematic literature search was performed in the PubMed and Cochrane library database up to March 2015. The quality assessment of diagnostic accuracy studies (QUADAS) was used to evaluate the quality of studies. Heterogeneous test on the included literature was performed by using the software Review Manager 5.3. The MetaDiSc 1.4 software was used to calculate the pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio; meanwhile the summary receiver operating characteristics (SROC) curve was drawn to compare the diagnostic performance. Results A total of 13 literatures were included in this study. In 8 literatures regarding HCC diagnosis based on Gd-EOB-DTPA-enhanced MRI, the pooled sensitivity: 0.90 (95% confidence interval (CI): 0.88–0.93); specificity: 0.89 (95% CI: 0.85–0.92); positive likelihood ratio: 8.60 (95% CI: 6.20–11.92); negative likelihood ratio: 0.10 (95% CI: 0.08–0.14) were obtained. The area under curve (AUC) and Q values were 0.96 and 0.90, respectively. In 5 literatures relating to HCC diagnosis by combination of Gd-EOB-DTPA-enhanced MRI and DWI sequence, the pooled sensitivity: 0.88 (95% CI: 0.85–0.91), specificity: 0.96 (0.94–0.97), positive likelihood ratio: 19.63 (12.77–30.16), negative likelihood ratio: 0.10 (0.07–0

  15. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Food..., other than black-eyed peas) 165 Promote color retention. Mayonnaise 75 Preservative. Ready-to-eat...

  16. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Food..., other than black-eyed peas) 165 Promote color retention. Mayonnaise 75 Preservative. Ready-to-eat...

  17. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Food..., other than black-eyed peas) 165 Promote color retention. Mayonnaise 75 Preservative. Ready-to-eat...

  18. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Food..., other than black-eyed peas) 165 Promote color retention. Mayonnaise 75 Preservative. Ready-to-eat...

  19. The effects of oral Cardax (disodium disuccinate astaxanthin) on multiple independent oxidative stress markers in a mouse peritoneal inflammation model: influence on 5-lipoxygenase in vitro and in vivo.

    PubMed

    Lockwood, Samuel F; Penn, Marc S; Hazen, Stanley L; Bikádi, Zsolt; Zsila, Ferenc

    2006-06-01

    Disodium disuccinate astaxanthin ('rac'-dAST; Cardax) is a water-dispersible C40 carotenoid derivative under development for oral and parenteral administration for cardioprotection of the at-risk ischemic cardiovascular patient. In experimental infarction models in animals (rats, rabbits, and dogs), significant myocardial salvage has been obtained, up to 100% at the appropriate dose in dogs. The documented mechanism of action in vitro includes direct scavenging of biologically produced superoxide anion; in vivo in rabbits, modulation of the complement activity of serum has also been shown. A direct correlation between administration of the test compound in animals and reductions of multiple, independent markers of oxidative stress in serum was recently obtained in a rat experimental infarction model. For the current study, it was hypothesized that oral Cardax administration would inhibit oxidative damage of multiple relevant biological targets in a representative, well-characterized murine peritoneal inflammation model. A previously developed mass spectrometry-based (LC/ESI/MS/MS) approach was used to interrogate multiple distinct pathways of oxidation in a black mouse (C57/BL6) model system. In vivo markers of oxidant stress from peritoneal lavage samples (supernatants) were evaluated in mice on day eight (8) after treatment with either Cardax or vehicle (lipophilic emulsion without drug) orally by gavage at 500 mg/kg once per day for seven (7) days at five (5) time points: (1) baseline prior to treatment (t=0); (2) 16 h following intraperitoneal (i.p.) injection with thioglycollate to elicit a neutrophilic infiltrate; (3) 4 h following i.p. injection of yeast cell wall (zymosan; t=16 h/4 h thioglycollate+zymosan); (4) 72 h following i.p. injection with thioglycollate to elicit monocyte/macrophage infiltration; and (5) 72 h/4 h thioglycollate+zymosan. A statistically significant sparing effect on the arachidonic acid (AA) and linoleic acid (LA) substrates was

  20. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-06-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M; Adalimumab, adefovir dipivoxil, adenosine triphosphate, albumin interferon alfa, alefacept, alemtuzumab, aminolevulinic acid hexyl ester, autologous renal tumor vaccine, azimilide hydrochloride; Bortezomib, bosentan, BR-1; C340, cantuzumab mertansine, caspofungin acetate, CGP-36742, CHAMPION everolimus-eluting coronary stent, cypher; Dalbavancin, darbepoetin alfa, desloratadine, duloxetine hydrochloride, dutasteride; Efalizumab, emtricitabine, enfuvirtide, erlosamide, ertapenem sodium, everolimus, ezetimibe; Flesinoxan hydrochloride, fosamprenavir calcium, FR-901228, frovatriptan; Gadofosveset sodium, gadomer-17, galiximab, gamma-hydroxybutyrate sodium, gefitinib; HuOKT3gamma1(Ala234-Ala235); IDN-6556, imatinib mesylate, iodine (I131) tositumomab, iseganan hydrochloride, ixabepilone; Keratinocyte growth factor; LB-80380, levocetirizine, liposomal doxorubicin, LMB-9, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Mecasermin, midostaurin, morphine hydrochloride; Natalizumab, nelfinavir, nesiritide, niacin/lovastatin; Olcegepant, omalizumab, oregovomab; Parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, perospirone hydrochloride, pexelizumab, pimecrolimus, prinomastat; Resiquimod, rhIGFBP-3, rhIGF-I/rhIGFBP-3, ritanserin, ro-31-7453, rosuvastatin calcium; SCIO-469, SDZ-SID-791, SU-11248, suberanilohydroxamic acid; Tadalafil, taxus, telithromycin, tenofovir disoproxil fumarate, TER-286, tezosentan disodium, TH-9507, tipifarnib, tipranavir, tolvaptan, tramadol hydrochloride/acetaminophen, travoprost, treprostinil sodium, tucaresol

  1. A Study of Pemetrexed in Children With Recurrent Cancer

    ClinicalTrials.gov

    2011-02-23

    Osteosarcoma; Medulloblastoma; Sarcoma, Ewing's; Neuroblastoma (Measurable Disease); Neuroblastoma (Metaiodobenzylguanidine; Positive Evaluable); Rhabdomyosarcoma; Ependymoma; Non-brainstem High-grade Glioma

  2. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-10-01

    [Methoxy-11c]PD-153035; Afamelanotide, Agalsidase beta, Alemtuzumab, Alkaline phosphatase, Amlodipine, Anecortave acetate, Apixaban, Aripiprazole, Atomoxetine hydrochloride; Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brimonidine tartrate/timolol maleate, Brivudine; Canakinumab, Cetuximab, Chlorotoxin, Cinaciguat; Dapagliflozin, Decitabine, Duloxetine hydrochloride; Elagolix sodium, Eplerenone, Eritoran tetrasodium, Escitalopram oxalate, Etoricoxib, Ezetimibe; Fospropofol disodium; G-207, Gabapentin enacarbil, Gefitinib, Golimumab; Human plasmin; Inotuzumab ozogamicin, Insulin glargine, Insulin glulisine, Istaroxime, Ixabepilone; KLH; Levodopa/carbidopa/entacapone; Miglustat, Mitumprotimut-T, MP-470; Oblimersen sodium, Olmesartan medoxomil; P53-SLP, PAN-811, Patupilone, Pazopanib hydrochloride, PC-515, Peginterferon alfa-2a, Pegylated arginine deiminase 20000, Pemetrexed disodium, Plitidepsin, Pregabalin; Rasagiline mesilate, Rotigotine; SCH-697243, Sirolimus-eluting stent, Sumatriptan succinate/naproxen sodium, Sunitinib malate; Tadalafil, Tapentadol hydrochloride, TMC-207; V-211, Valganciclovir hydrochloride; Zolpidem tartrate. PMID:19967103

  3. Gateways to clinical trials.

    PubMed

    Bayes, Miriam; Rabasseda, X; Prous, J R

    2007-04-01

    1E10, 101M; AAV-ASPA, agomelatine, aliskiren fumarate, alvimopan hydrate, ambrisentan, apaziquone, axitinib; Becatecarin, belagenpumatucel-L, BMS-201038; Cannabidiol, Cannabis sativa L. extract, capromorelin, CBP-501, cediranib, cetuximab, CHR-2797; Dapoxetine hydrochloride, degarelix acetate, desvenlafaxine succinate, dimethyl fumarate, dronedarone hydrochloride; Ecogramostim, eprodisate sodium; Falciparum merozoite protein-1/AS02A, fospropofol disodium; Gefitinib, glucarpidase, GTI-2040; Hepatitis C vaccine, HMR-4902, human proinsulin C-peptide, hyaluronic acid; Ipilimumab, ixabepilone; Lapatinib, lenalidomide, lestaurtinib, liposome encapsulated doxorubicin; Manidipine hydrochloride/delapril hydrochloride, metreleptin, MG-98, MGCD-0103, morphine glucuronide; Nebicapone; O6-benzylguanine, ofatumumab, olmesartan medoxomil/hydrochlorothiazide; PAN-811, pemetrexed disodium, perifosine, pertuzumab, Peru-15, pexelizumab, pirfenidone, pralatrexate, prasugrel; Quercetin; Rivaroxaban; Semaxanib, St. John's Wort extract; Ticagrelor, tomopenem, triplatin tetranitrate; Ulipristal acetate; Vandetanib, vatalanib succinate, vildagliptin; XK-469; ZT-1. PMID:17520107

  4. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3,4-DAP; Adefovir dipivoxil, ADL-10-0101, alefacept, alemtuzumab, alosetron hydrochloride, ALT-711, aprepitant, atazanavir sulfate, atlizumab, atvogen; Bortezomib; CETP vaccine, clevudine, crofelemer; DAC:GLP-1, darbepoetin alfa, decitabine, drotrecogin alfa (activated), DX-9065a; E-7010, edodekin alfa, emivirine, emtricitabine, entecavir, erlosamide, erlotinib hydrochloride, everolimus, exenatide; Fondaparinux sodium, frovatriptan, fulvestrant; Gemtuzumab ozogamicin, gestodene; Homoharringtonine, human insulin; Imatinib mesylate, indiplon, indium 111 (111In) ibritumomab tiuxetan, inhaled insulin, insulin detemir, insulin glargine, ivabradine hydrochloride; Lanthanum carbonate, lapatinib, LAS-34475, levetiracetam, liraglutide, lumiracoxib; Maxacalcitol, melagatran, micafungin sodium; Natalizumab, NSC-640488; Oblimersen sodium; Parecoxib sodium, PEG-filgrastim, peginterferon alfa-2(a), peginterferon alfa-2b, pexelizumab, pimecrolimus, pleconaril, pramlintide acetate, pregabalin, prucalopride; rAHF-PFM, Ranelic acid distrontium salt, ranolazine, rDNA insulin, recombinant human soluble thrombomodulin, rhGM-CSF, roxifiban acetate, RSD-1235, rubitecan, ruboxistaurin mesilate hydrate; SC-51, squalamine; Tegaserod maleate, telbivudine, tesaglitazar, testosterone gel, tezosentan disodium, tipranavir; Vatalanib succinate; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zoledronic acid monohydrate. PMID:14671684

  5. Disodium tris­(dioxidomolybdenum) bis­(diarsenate)

    PubMed Central

    Jouini, Raja; Zid, Mohamed Faouzi; Driss, Ahmed

    2012-01-01

    The asymmetric unit of the title compound, Na2(MoO2)3(As2O7)2, is composed of two cyclic MoAs2O11 units and an MoO6 corner-sharing octa­hedron. The anionic framework can be decomposed into two types of layers, viz. MoO2As2O7 and Mo2As2O14, which use mixed Mo—O—As and As—O—Mo bridges to achieve a new three-dimensional structure with two types of large channels in which the Na+ cations are located. Two O atoms are disordered and are located in two positions close to their initial positions with occupancy ratios of 0.612 (17):0.388 (17) and 0.703 (12):0.298 (12). PMID:22589750

  6. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., nonstandardized 75 Preservative. Dried lima beans (cooked canned) 310 Promote color retention. Egg product that is... cooked canned, other than dried lima beans, pink beans, and red beans) 365 Promote color retention... pie filling 100 Promote color retention. Pink beans (cooked canned) 165 Promote color...

  7. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., flavor, and/or product clarity. Dressings, nonstandardized 75 Preservative. Dried lima beans (cooked... Antigushing agent. French dressing 75 Preservative. Legumes (all cooked canned, other than dried lima beans, pink beans, and red beans) 365 Promote color retention. Mayonnaise 75 Do. Mushrooms (cooked canned)...

  8. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., nonstandardized 75 Preservative. Dried lima beans (cooked canned) 310 Promote color retention. Egg product that is... cooked canned, other than dried lima beans, pink beans, and red beans) 365 Promote color retention... pie filling 100 Promote color retention. Pink beans (cooked canned) 165 Promote color...

  9. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., nonstandardized 75 Preservative. Dried lima beans (cooked canned) 310 Promote color retention. Egg product that is... cooked canned, other than dried lima beans, pink beans, and red beans) 365 Promote color retention... pie filling 100 Promote color retention. Pink beans (cooked canned) 165 Promote color...

  10. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... million) Use Cabbage, pickled 220 Promote color, flavor, and texture retention. Canned carbonated soft drinks 33 Promote flavor retention. Canned white potatoes 110 Promote color retention. Clams...

  11. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... impurities other than those named to the extent that such impurities may be avoided by good manufacturing... amounts consistent with good manufacturing practices in the coloring of shampoos which are cosmetics....

  12. MRI With Gadoxetate Disodium in Measuring Tumors in Patients With Liver Cancer

    ClinicalTrials.gov

    2015-10-14

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage 0 Adult Hepatocellular Carcinoma; BCLC Stage A Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Localized Resectable Adult Liver Carcinoma

  13. Chelatable lead body burden (by calcium-disodium EDTA) and blood lead concentration in man

    SciTech Connect

    Brangstrup Hansen, J.P.; Dossing, M.; Paulev, P.E.

    1981-01-01

    The chelatable part of lead body burden was measured in 32 workers and seven office workers after an infusion test with CaNa/sub 2/EDTA. The workers had been exposed to lead at a lead and zinc processing unit for one to three years (mean one year). There was good correlation (r = 0.87) between blood lead and chelatable urinary lead excretion described by the equation y = 0 07.10/sup 0.46 x/. From this equation it can be predicted that the generally accepted limit value for chelatable urinary lead excretion, 0.42 ..mu..mol/mmol CaNa/sub 2/EDTA administered per 24 hours (3.1 ..mu..mol/24 hours or 650 ..mu..g/24 hours), corresponds to a blood lead concentration (PbB) of 1.7 ..mu..mol/l (or 35 ..mu..g/100 ml), which is lower than the commonly accepted limit value of 2.9 ..mu..mol/1 (or 60..mu..g/100 ml) for occupationally lead-exposed persons. There was a better correlation between the chelatable lead excretion and the urinary ALA-excretion (r = 0.45; p < 0.001) than between PbB and the urinary ALA-excretion (r = 0.26; p > 0.05).

  14. Use of gadoxetate disodium for functional MRI based on its unique molecular mechanism.

    PubMed

    Choi, YoonSeok; Huh, Jimi; Woo, Dong-Cheol; Kim, Kyung Won

    2016-01-01

    Gadolinium ethoxybenzyl dimeglumine (gadoxetate) is a recently developed hepatocyte-specific MRI contrast medium. Gadoxetate demonstrates unique pharmacokinetic and pharmacodynamic properties, because its uptake in hepatocytes occurs via the organic anion transporting polypeptide (OATP) transporter expressed at the sinusoidal membrane, and its biliary excretion via the multidrug resistance-associated proteins (MRPs) at the canalicular membrane. Based on these characteristics, gadoxetate-enhanced MRI can provide functional information on hepatobiliary diseases, including liver function estimation, biliary drainage evaluation and characterization of hepatocarcinogenesis. In addition, understanding its mode of action can provide an opportunity to use gadoxetate for cellular and molecular imaging. Radiologists and imaging scientists should be familiar with the basic mechanism of gadoxetate and OATP/MRP transporters. PMID:26693795

  15. The poor bioavailability of elemental iron in corn masa flour is not affected by disodium EDTA.

    PubMed

    Walter, Tomas; Pizarro, Fernando; Boy, Erick; Abrams, Steven A

    2004-02-01

    The most sustainable way to eradicate iron deficiency is through food fortification. Elemental iron powders are commonly utilized as fortificants due to their low cost and few sensory problems. However, their bioavailability is unknown. Our goals were to measure the bioavailability of elemental iron in Mexican style corn masa flour tortillas and to evaluate the effects of Na(2)EDTA. We used a stable isotope of H(2)-reduced iron powder, with and without Na(2)EDTA in tortillas prepared with corn masa flour. Two groups of 5- to 7-y-old children (n = 12/group) were fed tortillas to which was added 3 mg/100 g of H(2)-reduced (58)Fe with a mean particle size of 15 micro m. In one group, Na(2)EDTA was incorporated at a ratio of 1:2 mol/mol. The next day, (57)Fe ascorbate was given as a reference dose. After 14 d, blood samples were analyzed for isotopic enrichment. When normalized to 40% absorption of the reference dose, the geometric mean (+/-range 1 SD) bioavailability of reduced iron in tortilla was 3.8% (2.7-5.3). The addition of Na(2)EDTA, tended to increase it (P = 0.18) to 5.1% (2.8-9.2). This observed low absorption was compounded by the use of iron isotopes with smaller particle size (mean diameter 15 micro m) than typical of commercial elemental iron powder (<45 micro m). We conclude that H(2)-reduced iron powder is an ineffective fortificant in corn tortillas. PMID:14747675

  16. Ph 1 Study in Subjects With Tumors Requiring Arginine to Assess ADI-PEG 20 With Pemetrexed and Cisplatin

    ClinicalTrials.gov

    2016-08-10

    Pleural Mesothelioma Malignant Advanced; Peritoneal Mesothelioma Malignant Advanced; Non-squamous Non-small Cell Lung Carcinoma Stage IIIB/IV (NSCLC); Metastatic Uveal Melanoma; Hepatocellular Carcinoma (HCC); Glioma; Sarcomatoid Cancers

  17. Pharmacokinetics of peginterferons.

    PubMed

    Zeuzem, Stefan; Welsch, Christoph; Herrmann, Eva

    2003-01-01

    Two polyethylene glycol (PEG)-modified interferons are approved for the treatment of chronic hepatitis C. The pharmocokinetic properties of the branched 40 kDa pegylated interferon alfa-2a differ from the linear 12 kDa pegylated interferon alfa-2b. The absorption half-life of standard interferon alfa is 2.3 hours, while absorption half-lives for peginterferon alfa-2a and alfa-2b are 50 hours and 4.6 hours, respectively. The volume of distribution for peginterferon alfa-2a is considerably restricted, while the volume of distribution for peginterferon alfa-2b is only approximately 30% lower than that for conventional interferon. Because of its large size, the 40 kD peginterferon alfa-2a has a more than 100-fold reduction in renal clearance compared with conventional interferon alfa. Clearance of peginterferon alfa-2b is about one-tenth that of unmodified interferon alfa. Although data are limited, both drugs appear to show differences in the initial viral decay pattern in patients with chronic hepatitis C. However, it remains unknown whether these differences in the initial viral decline predict differences in the primary clinical endpoint, sustained virological response. PMID:12934165

  18. African Americans Respond Poorly to Hepatitis C Treatment

    ERIC Educational Resources Information Center

    Black Issues in Higher Education, 2004

    2004-01-01

    African Americans have a significantly lower response rate to treatment for chronic hepatitis C than non-Hispanic Whites, according to a new study led by Duke University Medical Center researchers. Some African Americans--19 percent--did respond to the drug combination of peginterferon alfa-2b and ribavirin. But in non-Hispanic Whites with the…

  19. Testing Adjuvant Ipilimumab in Advanced Melanoma

    Cancer.gov

    In this clinical trial, patients with stage III or stage IV melanoma that has been completely resected will be randomly assigned to receive post-surgical treatment with either ipilimumab or high-dose interferon alfa-2b, the current standard of care.

  20. Peginterferon alfa-2a plus ribavirin for treating chronic hepatitis C virus infection: analysis of Mexican patients included in a multicenter international clinical trial.

    PubMed

    Bosques-Padilla, Francisco; Trejo-Estrada, Rafael; Campollo-Rivas, Octaivio; Cortez-Hernández, Carlos; Dehesa-Violante, Margarita; Maldonado-Garza, Héctor; Pérez-Gómez, Rául; Cabrera-Valdespino, Armando

    2003-01-01

    Treatment with polyethylene glycol-modified interferon alfa-2a (peginterferon) alone produces significantly higher sustained antiviral responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. Thirty-two patients were randomly assigned to treatment, and received at least one dose of medication consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin (1,000 or 1,200 mg, depending on body weight) (n = 14), weekly peginterferon alfa-2a plus daily placebo (n = 6), or three million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks (n = 12). More patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) than patients who received interferon alfa-2b plus ribavirin (7/14 vs. 4/12) or peginterferon alfa-2a plus placebo (0/6). The overall safety profiles of the three treatment regimens were similar. In conclusion, for patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained viral reduction compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone. PMID:15115965

  1. 40 CFR 180.1121 - Boric acid and its salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Boric acid and its salts, borax... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1121 Boric acid and its... the requirement of a tolerance is established for residues of the pesticidal chemical boric acid...

  2. 40 CFR 180.1121 - Boric acid and its salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Boric acid and its salts, borax... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1121 Boric acid and its... the requirement of a tolerance is established for residues of the pesticidal chemical boric acid...

  3. 40 CFR 180.1121 - Boric acid and its salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Boric acid and its salts, borax... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1121 Boric acid and its... the requirement of a tolerance is established for residues of the pesticidal chemical boric acid...

  4. 40 CFR 180.1121 - Boric acid and its salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Boric acid and its salts, borax... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1121 Boric acid and its... the requirement of a tolerance is established for residues of the pesticidal chemical boric acid...

  5. 40 CFR 180.1121 - Boric acid and its salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Boric acid and its salts, borax... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1121 Boric acid and its... the requirement of a tolerance is established for residues of the pesticidal chemical boric acid...

  6. Evaluation of the disodium salt of 4,4'-diamino-2,2'-stilbene disulfonic acid for estrogenic activity.

    PubMed

    Hostetler, K A; Leach, M W; Hyde, T E; Wei, L L

    1996-06-01

    4,4'-Diamino-2,2'-stilbene disulfonic acid (DAS), a key intermediate in the synthesis of dyes and fluorescent whitening agents, has been purported to have weak estrogenic properties based on apparent structural similarity with diethylstibestrol (DES) and unsubstantiated reports of male reproductive dysfunction in an industrial setting. In weanling rats, high doses of DAS (300 mg/kg ip; 1000-3000 mg/kg oral) have been associated with modest increases in the uterus/body weight ratio (Smith & Quinn, 1992). In order to more directly and definitively determine if DAS possesses estrogenic activity, in vitro studies were conducted to establish its relative binding affinity to the human estrogen receptor (ER) in MCF-7 cells, a well-characterized breast cancer cell line. At concentrations approaching its solubility limit (10(-4) M), DAS failed to display [3H]-17beta-estradiol (E2) from the ER. In contrast, DES and E2 demonstrated characteristic competitive binding curves (50% displacement of 3H-E2 at 3.33 x 10(-9) and 1.33 x 10(-8) M, respectively). Parallel in vivo comparisons of DAS (10 or 30 mg/animal) and DES (1 or 3 microgram/animal) were also conducted to assess uterotropic effects. After three daily subcutaneous injections, DAS did not induce uterine weight gain. In contrast, DES consistently and markedly increased uterine weight and induced uterine water imbibition, with the latter effect being absent in DAS-treated rats. Under these experimental conditions, DAS was shown to possess negligible, if any, estrogenic activity, despite apparent structural similarity with known estrogens. PMID:8642622

  7. Crystal structure of disodium dicobalt(II) iron(III) tris­(orthophosphate) with an alluaudite-like structure

    PubMed Central

    Bouraima, Adam; Assani, Abderrazzak; Saadi, Mohamed; Makani, Thomas; El Ammari, Lahcen

    2015-01-01

    The title compound, Na2Co2Fe(PO4)3, was synthesized by a solid-state reaction. This new stoichiometric phase crystallizes in an alluaudite-like structure. In this structure, all atoms are in general positions except for four atoms which are located at the special positions of the C2/c space group. One Co atom, one P and one Na atom are all located on Wyckoff position 4e (2), while the second Na atom is located on an inversion centre 4a (-1). The other Co and Fe atoms occupy a general position with a statistical distribution. The open framework results from [(Co,Fe)2O10] units of edge-sharing [(Co,Fe)O6] octa­hedra, which alternate with [CoO6] octa­hedra that form infinite chains running along the [10-1] direction. These chains are linked together through PO4 tetra­hedra by the sharing of vertices so as to build layers perpendicular to [010]. The three-dimensional framework is accomplished by the stacking of these layers, leading to the formation of two types of tunnels parallel to [010] in which the Na+ cations are located, each cation being surrounded by eight O atoms. PMID:25995879

  8. Effects of Orally Administered Pyrroloquinoline Quinone Disodium Salt on Dry Skin Conditions in Mice and Healthy Female Subjects.

    PubMed

    Nakano, Masahiko; Kamimura, Ayako; Watanabe, Fumiko; Kamiya, Toshikazu; Watanabe, Daisuke; Yamamoto, Etsushi; Fukagawa, Mitsuhiko; Hasumi, Keiji; Suzuki, Eriko

    2015-01-01

    Pyrroloquinoline quinone (PQQ) is a coenzyme involved in the redox-cycling system. The supplemental use of PQQ has been examined based on its properties as an antioxidant and redox modulator. Although an animal study on deficiency of PQQ suggested that PQQ contributes to skin conditions, its efficacy in humans has not been reported. The present study aimed to investigate the effects of orally administered PQQ on skin moisture, viscoelasticity, and transepidermal water loss (TEWL) both in dry skin mouse models and in healthy female subjects with a subjective symptom of dry skin. In our dry skin mouse model study, oral intake of PQQ (0.0089%, w/w, in the diet for 6 wk) significantly decreased the number of mast cells in the dermis and the number of CD3⁺ T-cells in the epidermis. In our human study, oral intake of PQQ (20 mg/d for 8 wk) significantly inhibited the increase in TEWL on the forearm. Finally, subject questionnaires showed positive impressions for the improvement of skin conditions. These results suggest that oral intake of PQQ improves skin conditions both in female subjects with dry skin and in mice with a compromised skin barrier function. PMID:26226961

  9. Comparative effects of vetiver oil, nootkatone and disodium octaborate tetrahydrate on Coptotermes formosanus and its symbiotic fauna.

    PubMed

    Maistrello, Lara; Henderson, Gregg; Laine, Roger A

    2003-01-01

    The potential of vetiver oil and nootkatone as wood treatments against Coptotermes formosanus Shiraki was examined by assessing the effects on termite tunneling, feeding activity and survival, and the consequences on the symbiont protozoa responsible for wood digestion. Comparisons were made with non-treated wood (control), wood treated with the borate compound Tim-Bor (a commonly used lumber preservative) and absence of a food source (starved termites), using choice and no-choice tests. All wood slices were prepared at the same time using a 10 g liter(-1) solution of each substance and were tested in four different sessions over one year to investigate longevity of the effects. Termites had to tunnel through sand to exploit the food sources, consisting of two wood slices, placed on opposite sides of the experimental enclosure. No-choice tests showed that in the presence of vetiver oil or nootkatone, tunneling activity was always the lowest; wood consumption, termite survival and flagellate numbers and species distribution were significantly different from the control and similar to the results obtained for starved termites and with Tim-Bor-treated wood. Nootkatone negatively affected termites for 12 months and was longer lasting than vetiver oil. In choice tests, when vetiver oil or nootkatone were present, termites exhibited a significant preference for non-treated wood. Our results confirmed both the toxicity and absence of repellency of Tim-Bor. Vetiver oil and especially nootkatone affected Formosan subterranean termites and their protozoa, acting as arrestants, repellents and feeding deterrents, and represent a promising natural alternative for the control of this invasive pest. PMID:12558100

  10. Gateways to clinical trials. December 2008.

    PubMed

    Tomillero, A; Moral, M A

    2008-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a; Abatacept, ABT-263, Adalimumab, Aflibercept, Afobazole, Aliskiren fumarate, Anakinra, Atazanavir/ritonavir, Aviscumine, Axitinib, Azacitidine; Bevacizumab, Biphasic insulin aspart, Bortezomib, Briobacept; Carmoterol hydrochloride, CCX-282, Ceftobiprole medocaril, Certolizumab pegol, Cetuximab; Darifenacin hydrobromide, Dasatinib, Denosumab, Doripenem, Duloxetine hydrochloride; E-7080, Epratuzumab, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe/simvastatin; Gefitinib, Golimumab; gamma-Hydroxybutyrate sodium; Imatinib mesylate, Insulin detemir, Insulin glulisine, IVX-0142; Laquinimod sodium, Linezolid, Lopinavir/ritonavir; Ocrelizumab, Omalizumab; Parecoxib sodium, Pemetrexed disodium, Pregabalin; Rosuvastatin calcium, Rotigotine; Sorafenib, Sugammadex sodium; Tapentadol hydrochloride, Tenofovir disoproxil fumarate/emtricitabine, Tocilizumab; Ularitide, Ustekinumab; Valsartan/amlodipine besylate, Varenicline tartrate, Vatalanib succinate, Vildagliptin, Vorinostat. PMID:19271026

  11. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-01-01

    [90Y-DOTA-Tyr3]octreotate, Abatacept, ABT-888, ACE-011, Adefovir dipivoxil, Alosetron hydrochloride, Aminolevulinic acid methyl ester, Amlodipine, Apaziquone, Aripiprazole, AS-101, Atomoxetine hydrochloride, Atrasentan, Azacitidine; Bevacizumab, Biphasic insulin aspart, Bortezomib, Bosentan, Brivanib alaninate; CERE-120, Cetuximab, Ciclesonide, Cinacalcet hydrochloride, Combretastatin A-1 phosphate, Conatumumab, CT-322; Dabigatran etexilate, Darunavir, Deforolimus, Desloratadine, Doripenem, Doxorubicin eluting beads, Duloxetine hydrochloride, Dutasteride; Escitalopram oxalate, Eszopiclone, Etravirine, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fluticasone furoate, Fondaparinux sodium; Gabapentin enacarbil, Ghrelin (human), Golimumab; IC-51, IDM-2, JX-594; Lidocaine/prilocaine, Liraglutide, Lopinavir, Lopinavir/ritonavir, Lumiracoxib; Men ACWY, MxdnG1; Naproxcinod; OBP-301, Omalizumab; Paclitaxel nanoparticles, Pasireotide, Pazopanib hydrochloride, Pegaptanib octasodium, Peginterferon alfa-2a, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Prasterone, Pregabalin; Raclopride, Ranelic acid distrontium salt, Ranibizumab, RB-006, Recombinant human relaxin H2, REG1, Regadenoson, Reximmune-C, Rilonacept; Saxagliptin, SCH-697243, Solifenacin succinate, Sorafenib; Tadalafil, Tapentadol hydrochloride, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tipifarnib, Tolvaptan; Vardenafil hydrochloride hydrate, Vicriviroc, Volociximab, Vorinostat; WB-1001; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:19798455

  12. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-06-01

    (+)-Dapoxetine hydrochloride, (R)-Etodolac; Abatacept, ABT-510, Adalimumab, Agatolimod sodium, Alemtuzumab, Alvocidib hydrochloride, Aminolevulinic acid methyl ester, Aripiprazole, AS01B, AS02B, AS02V, Azacitidine; Becatecarin, Bevacizumab, Bevirimat, Bortezomib, Bremelanotide; CAIV-T, Canfosfamide hydrochloride, CHR-2797, Ciclesonide, Clevidipine; Darbepoetin alfa, Decitabine, Degarelix acetate, Dendritic cell-based vaccine, Denosumab, Desloratadine, DMXB-Anabaseine, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Eicosapentaenoic acid/docosahexaenoic acid, Eletriptan, Enzastaurin hydrochloride, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Ferumoxytol, Fesoterodine fumarate, Fulvestrant; Gefitinib, GM-CSF DNA, GSK-690693; H5N1 avian flu vaccine, Hepatitis B hyperimmunoglobulin, Human Fibroblast Growth Factor 1, Hypericin-PVP; Icatibant acetate, Iclaprim, Immunoglobulin intravenous (human), Ipilimumab, ISS-1018; L19-IL-2, Lapuleucel-T, Laropiprant, Liposomal doxorubicin, LP-261, Lumiracoxib, LY-518674; MDV-3100, MGCD-0103, Mirabegron, MyoCell; NASHA/Dx, Niacin/laropiprant; O6-Benzylguanine, Ocrelizumab, Olmesartan medoxomil, Omalizumab; P-276-00, Paclitaxel nanoparticles, Paclitaxel nanoparticles, Padoporfin, Paliperidone, PAN-811, Pegaptanib octasodium, Pegfilgrastim, Pemetrexed disodium, PF-00299804, Pimecrolimus, Prasugrel, Pregabalin; Reolysin, Rimonabant, Rivaroxaban, Rosuvastatin calcium; Satraplatin, SCH-697243,Selenite sodium, Silodosin, Sorafenib, Sunitinib malate; Talarozole, Taxus, Temsirolimus, Tocilizumab, Tolevamer potassium sodium, Tremelimumab, TTP-889; Uracil; V-260, Valsartan/amlodipine besylate, Vardenafil hydrochloride hydrate, Varenicline tartrate, Varespladib, Vitespen, Voclosporin, VX-001; Xience V; Zotarolimus-eluting stent. PMID:18806898

  13. The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication

    PubMed Central

    Hooper, C E; Lyburn, I D; Searle, J; Darby, M; Hall, T; Hall, D; Morley, A; White, P; Rahman, N M; De Winton, E; Clive, A; Masani, V; Arnold, D T; Dangoor, A; Guglani, S; Jankowska, P; Lowndes, S A; Harvey, J E; Braybrooke, J P; Maskell, N A

    2015-01-01

    Background: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care. Methods: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil–lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months. Findings: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272–576) days vs NLR⩾4, 257 (IQR 147–490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001). Interpretation: Neutrophil–lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients' treatment response. PMID:25756396

  14. Retinopathy in chronic hepatitis C patients during interferon treatment with ribavirin

    PubMed Central

    Jain, K; Lam, W; Waheeb, S; Thai, Q; Heathcote, J

    2001-01-01

    AIM—To assess the ocular effect of interferon alfa 2b prescribed with ribavirin in patients undergoing therapy for chronic hepatitis C.
METHODS—19 patients with chronic hepatitis C who satisfied the follow up criteria were assessed for ocular complications using slit lamp biomicroscopy and indirect ophthalmoscopy before, during, and after the treatment at regular intervals.
RESULTS—8/19 patients, while on treatment, developed an asymptomatic retinopathy. Among these 3/8 were relapsers and 5/9 were non-responders to interferon monotherapy. All retinal changes faded, often while the patients continued the therapy. There was no significant association in occurrence of retinopathy with haematological and/or biochemical changes.
CONCLUSION—Retinopathy was more common in interferon monotherapy non-responders than relapsers when treated with interferon alfa 2b with the addition of ribavirin. The changes were transient, disappearing while the patients were still being treated.

 PMID:11567959

  15. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2006-05-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com/. This issue focuses on the following selection of drugs: Adalimumab, adenosine triphosphate, alemtuzumab, alendronate sodium/cholecalciferol, aliskiren fumarate, AMGN-0007, aminolevulinic acid methyl ester, anakinra, anidulafungin, aripiprazole, atomoxetine hydrochloride; Bevacizumab, bosentan; Calcipotriol/beta methasone dipropionate, caldaret hydrate, caspofungin acetate, cetuximab, cinacalcet hydrochloride, clopidogrel, cocaine-BSA conjugate, conivaptan hydrochloride, Cypher; Darbepoetin alfa, delmitide, desloratadine, desmoteplase, desoxyepothilone B, disufenton sodium, DU-176b, duloxetine hydrochloride, dutasteride; EBV-specific CTLs, ecogramostim, edodekin alfa, efalizumab, eletriptan, emtricitabine, entecavir, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, etoricoxib, everolimus, ezetimibe; Fanapanel, fondaparinux sodium; Gefitinib, GTI-2040, GW-501516; Her2 E75-peptide vaccine, human insulin; Ibogaine, icatibant acetate, Id-KLH vaccine, imatinib mesylate, immune globulin subcutaneous [human], indacaterol, inolimomab, ipilimumab, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, lanthanum carbonate, lenalidomide, levocetirizine, levodopa methyl ester hydrochloride/carbidopa, levodopa/carbidopa/entacapone, lidocaine/prilocaine; Maraviroc, mecasermin, melevodopa hydrochloride, mepolizumab, mitumomab; Nesiritide; Omalizumab, oral insulin; Parathyroid hormone (human recombinant), patupilone, pegaptanib sodium, PEG-filgrastim, pemetrexed disodium, photochlor, pimecrolimus, posaconazole, prasterone, prasugrel, pregabalin, prilocaine, PRX-00023; QS-21; Ranibizumab, ranirestat, rhodamine 123, rotigaptide; Sarcosine, sirolimus

  16. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2006-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABT-510, adalimumab, alefacept, ambrisentan, aminolevulinic acid methyl ester, armodafinil, aselizumab, asenapine maleate, azelnidipine; Bevacizumab, bexarotene, bimosiamose, biphasic insulin aspart, bortezomib, bosentan, BQ-123; C340, cannabidiol, caspofungin acetate, CC-4047, certolizumab pegol, cetuximab, ciclesonide, cilansetron, Cypher; Dabigatran etexilate, darbepoetin alfa, darifenacin hydrobromide, desloratadine, dexosome vaccine (melanoma), dimethyl fumarate, dronabinol/cannabidiol, drospirenone, drospirenone/estradiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Efalizumab, eglumetad hydrate, emoxipin hydrochloride, eplerenone, erlotinib hydrochloride, escitalopram oxalate, etonogestrel/ethinylestradiol; Garenoxacin mesilate, gamma-hydroxybutyrate sodium, gefitinib; H5N1 pandemic influenza vaccine, human growth hormone-(177-191), human insulin; Indacaterol, INKP-100, INKP-102, insulin glargine, i.v. gamma-globulin; KLH; Lapatinib, L-arginine hydrochloride, lasofoxifene tartrate, levocetirizine, licochalcone A, LMI vaccine, lomefloxacin, lubiprostone, lumiracoxib; Miglustat, mycograb; Natalizumab, NCX-4016, nortopixantrone hydrochloride; Olmesartan medoxomil, omalizumab, oral insulin, OrM3; Parathyroid hormone (human recombinant), parecoxib sodium, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, pemetrexed disodium, pexelizumab, photochlor, pimecrolimus, pneumococcal 7-valent conjugate vaccine, polyphenon E; R-126638, R-411, resveratrol, roflumilast, RS-86, ruboxistaurin mesilate hydrate, rupatadine fumarate; Sipuleucel-T, somatropin, St. John's Wort extract; Tadalafil, Taxus

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X

    2008-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prouse Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 3F8; Abatacept, ABT-263, Adalimumab, AG-7352, Agatolimod sodium, Alfimeprase, Aliskiren fumarate, Alvimopan hydrate, Aminolevulinic acid hexyl ester, Ammonium tetrathiomolybdate, Anakinra, Aripiprazole, AS-1404, AT-9283, Atomoxetine hydrochloride, AVE-1642, AVE-9633, Axitinib, AZD-0530; Becocalcidiol, Belotecan hydrochloride, Bevacizumab, BG-9928, BIBF-1120, BMS-275183, Bortezomib, Bosentan; Catumaxomab, Cetuximab, CHR-2797, Ciclesonide, Clevidipine, Cypher, Cytarabine/daunorubicin; Darifenacin hydrobromide, Darunavir, Denosumab, Desvenlafaxine succinate, Disufenton sodium, Duloxetine hydrochloride, Dutasteride; Eculizumab, Efalizumab, Eicosapentaenoic acid/docosahexaenoic acid, Eplerenone, Epratuzumab, Erlotinib hydrochloride, Escitalopram oxalate, Ethynylcytidine, Etravirine, Everolimus, Ezetimibe; Fulvestrant; Garenoxacin mesilate, Gefitinib, Gestodene; HI-164, Hydralazine hydrochloride/isosorbide dinitrate; Icatibant acetate, ICX-RHY, Idraparinux sodium, Indacaterol, Ispronicline, Ivabradine hydrochloride, Ixabepilone; KB-2115, KW-2449; L-791515, Lapatinib ditosylate, LGD-4665, Licofelone, Liposomal doxorubicin, Lisdexamfetamine mesilate, Lumiracoxib; Methoxy polyethylene glycol-epoetin-beta, Miglustat, Mipomersen sodium, Mitumprotimut-T, MK-0822A, MK-0974; Nelarabine; Obatoclax mesylate, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paliperidone, Palonosetron hydrochloride, Panitumumab, Pegfilgrastim, Peginterferon alfa-2a, Pemetrexed disodium, Perospirone hydrochloride, Pertuzumab, Pimecrolimus, Pitrakinra, Pixantrone maleate, Posaconazole, Pregabalin; Quercetin; RALGA, Raltegravir

  18. Cytotoxic Activity of Anticancer Drugs on Hepatocellular Carcinoma Cells in Hypoxic-Hyponutritional Culture

    PubMed Central

    Li, Qiang; Zhu, Lin-Zhong; Yang, Ren-Jie; Zhu, Xu

    2014-01-01

    To investigate which anticancer drugs and combination of dual drugs could further promote the inhibition of cell growth in vitro against HCC cell line (HepG2) in the hypoxic and hyponutritional culture medium (HHCM) mimicked the different scenarios of transcatheter arterial chemoembolization (TACE). The cells of hepatocellular carcinoma (HCC) treated by TACE suffered various hypoxia and hyponutrition. The cells were treated for 2 hours, 4 hours, 6 hours, and 24 hours, respectively, using 10 drugs including epirubicin (EPI), cisplatin (DDP), mitomycin-C (MMC), oxaliplatin (OXA), hydroxycamptothecin (HCPT), 5-fluorouracil (5-FU), gemcitabine (GEM), docetaxel (DTX), thiotepa (TSPA), and pemetrexed disodium (PEM) in 4 concentrations of HHCM (5%, 10%, 25%, and 50%, respectively) mimicking the scenario of TACE and were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells treated with combinations of dual drugs for 24 hours were also tested. The sensitive drugs with inhibition rates more than 30% were EPI, MMC, HCPT, OXA, and PEM in 4 types of HHCMs. The sensitivity of the cells to treatment with drugs for 24 hours was significantly higher than the sensitivity of the cells to treatment with drugs for 2 hours in 5%, 10%, and 25% HHCM. The sensitivity of the combination of dual drugs was no more than the sensitivity of the single drug with higher sensitivity in 4 concentrations of HHCM. EPI, MMC, HCPT, OXA, and PEM exhibited cytotoxic activity against HepG2 cells in various hypoxia and hyponutrition states. Prolonging the time of exposure could increase the sensitivity of drug, and the combination of dual drugs cannot enhance the cytotoxic effect. PMID:25437582

  19. Cytotoxic activity of anticancer drugs on hepatocellular carcinoma cells in hypoxic-hyponutritional culture.

    PubMed

    Li, Qiang; Zhu, Lin-Zhong; Yang, Ren-Jie; Zhu, Xu

    2014-01-01

    To investigate which anticancer drugs and combination of dual drugs could further promote the inhibition of cell growth in vitro against HCC cell line (HepG2) in the hypoxic and hyponutritional culture medium (HHCM) mimicked the different scenarios of transcatheter arterial chemoembolization (TACE). The cells of hepatocellular carcinoma (HCC) treated by TACE suffered various hypoxia and hyponutrition. The cells were treated for 2 hours, 4 hours, 6 hours, and 24 hours, respectively, using 10 drugs including epirubicin (EPI), cisplatin (DDP), mitomycin-C (MMC), oxaliplatin (OXA), hydroxycamptothecin (HCPT), 5-fluorouracil (5-FU), gemcitabine (GEM), docetaxel (DTX), thiotepa (TSPA), and pemetrexed disodium (PEM) in 4 concentrations of HHCM (5%, 10%, 25%, and 50%, respectively) mimicking the scenario of TACE and were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells treated with combinations of dual drugs for 24 hours were also tested. The sensitive drugs with inhibition rates more than 30% were EPI, MMC, HCPT, OXA, and PEM in 4 types of HHCMs. The sensitivity of the cells to treatment with drugs for 24 hours was significantly higher than the sensitivity of the cells to treatment with drugs for 2 hours in 5%, 10%, and 25% HHCM. The sensitivity of the combination of dual drugs was no more than the sensitivity of the single drug with higher sensitivity in 4 concentrations of HHCM. EPI, MMC, HCPT, OXA, and PEM exhibited cytotoxic activity against HepG2 cells in various hypoxia and hyponutrition states. Prolonging the time of exposure could increase the sensitivity of drug, and the combination of dual drugs cannot enhance the cytotoxic effect. PMID:25437582

  20. A co-crystal of nona-hydrated disodium(II) with mixed anions from m-chloro-benzoic acid and furosemide.

    PubMed

    London, Bianca King; Claville, Michelle O Fletcher; Babu, Sainath; Fronczek, Frank R; Uppu, Rao M

    2015-10-01

    In the title compound, [Na2(H2O)9](C7H4ClO2)(C12H10ClN2O5S) {systematic name: catena-poly[[[triaquasodium(I)]-di-μ-aqua-[triaquasodium(I)]-μ-aqua] 3-chlorobenzoate 4-chloro-2-[(furan-2-ylmethyl)amino]-5-sulfamoylbenzoate]}, both the original m-chloro-benzoic acid and furosemide exist with deprotonated carboxyl-ates, and the sodium cations and water mol-ecules exist in chains with stoichiometry [Na2(OH2)9](2+) that propagate in the [-110] direction. Each of the two independent Na(+) ions is coordinated by three monodentate water mol-ecules, two double-water bridges, and one single-water bridge. There is considerable cross-linking between the [Na2(OH2)9](2+) chains and to furosemide sulfonamide and carboxyl-ate by inter-molecular O-H⋯O hydrogen bonds. All hydrogen-bond donors participate in a complex two-dimensional array parallel to the ab plane. The furosemide NH group donates an intra-molecular hydrogen bond to the carboxyl-ate group, and the furosemide NH2 group donates an intra-molecular hydrogen bond to the Cl atom and an inter-molecular one to the m-chloro-benzoate O atom. The plethora of hydrogen-bond donors on the cation/water chain leads to many large rings, up to graph set R 4 (4)(24), involving two chains and two furosemide anions. The chloro-benzoate is involved in only one R 2 (2)(8) ring, with two water mol-ecules cis-coordinated to Na. The furan O atom is not hydrogen bonded. PMID:26594422

  1. 21 CFR 73.3129 - Disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]amino]-9,10-dihydro-9,10...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... may be used as a color additive in contact lenses in amounts not to exceed the minimum reasonably... Food, Drug, and Cosmetic Act with respect to the contact lenses in which the additive is used....

  2. Response of immune response genes to adjuvants poly [di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP), CpG oligodeoxynucleotide and emulsigen at intradermal injection site in pigs.

    PubMed

    Magiri, R B; Lai, K; Chaffey, A M; Wilson, H L; Berry, W E; Szafron, M L; Mutwiri, G K

    2016-07-01

    Understanding the mechanisms by which adjuvants mediate their effects provide critical information on how innate immunity influences the development of adaptive immunity. Despite being a critical vaccine component, the mechanisms by which adjuvants mediate their effects are not fully understood and this is especially true when they are used in large animals. This lack of understanding limits our ability to design effective vaccines. In the present study, we administered polyphosphazene (PCEP), CpG oligodeoxynucleotides (CpG), emulsigen or saline via an intradermal injection into pigs and assessed the impact on the expression of reported 'adjuvant response genes' over time. CpG induced a strong upregulation of the chemokine CXL10 several 'Interferon Response Genes', as well as TNFα, and IL-10, and a down-regulation of IL-17 genes. Emulsigen upregulated expression of chemokines CCL2 and CCL5, proinflammatory cytokines IL-6 and TNFα, as well as TLR9, and several IFN response genes. PCEP induced the expression of chemokine CCL2 and proinflammatory cytokine IL-6. These results suggest that emulsigen and CpG may promote recruitment of innate immune cells and Th1 type cytokine production but that PCEP may promote a Th-2 type immune response through the induction of IL-6, an inducer of B cell activity and differentiation. PMID:27269793

  3. Poly[[di-μ-aqua-(μ-4-formyl-2-meth­oxy­phenol­ato)disodium] 4-formyl-2-meth­oxy­phenolate

    PubMed Central

    Asghar, Muhammad Nadeem; Şahin, Onur; Arshad, Muhammad Nadeem; Mazhar, Uzma; Khan, Islam Ullah; Büyükgüngör, Orhan

    2010-01-01

    In the title coordination polymer, {[Na2(C8H7O3)(H2O)4](C8H7O3)}n, all the non-H atoms except the water O atoms lie on a crystallographic mirror plane. One sodium cation is bonded to four water O atoms and one vanillinate O atom in a distorted square-based pyramidal arrangement; the other Na+ ion is six-coordinated by four water O atoms and two vanillinate O atoms in an irregular geometry. One of the vanillinate anions is directly bonded to two sodium ions, whilst the other only inter­acts with the polymeric network by way of hydrogen bonds. In the crystal, a two-dimensional polymeric array is formed; this is reinforced by O—H⋯O hydrogen bonds, which generate R 2 1(6) and R 2 2(20) loops. PMID:21579628

  4. Pemetrexed Long-Term Maintenance Treatment Leading to Multiple Finger Amputation; Cardiovascular Complications After Energy Drink Consumption; Compartment Syndrome Due to Extravasation of Intravenous Contrast; Blue-Gray Mucocutaneous Discoloration with Ezogabine

    PubMed Central

    Mancano, Michael A.

    2015-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s Med Watch program and Temple University School of Pharmacy. ISMP is an FDA Med Watch partner. PMID:25717203

  5. How to Read a Food Label: Tips for People with Chronic Kidney Disease (CKD)

    MedlinePlus

    ... foods with potassium on the ingredient list. Ingredients: Tomato juice, Vegetable juice blend, Potassium chloride, Sugar, Magnesium, Salt, Vitamin C (Ascorbic acid), Citric acid, Spice extract, Flavoring, Disodium inosinate, Disodium ...

  6. 40 CFR 721.9795 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[(4,6-dichloro-1,3,5-triazin-2-yl) amino...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-ethenediyl)bis -, disodium salt, substituted with dialkyl amines (generic). 721.9795 Section 721.9795... Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with dialkyl amines (generic). (a... generically as a benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with...

  7. Calcium Free Asbestos for Fuel Cells

    NASA Technical Reports Server (NTRS)

    Snitzer, B. A.

    1983-01-01

    Organic-acid salt removes unwanted calcium without weakening asbestos. Asbestos mixed with disodium ethylene diamine tetraacetic acid (disodium EDTA) in water and agitated for 2 hours. After disodium EDTA solution is drained away, asbestos contains only 0.02 to 0.1 percent calcium. Fiber structure of asbestos unaffected.

  8. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: 131I-chTNT; Abatacept, adalimumab, alemtuzumab, APC-8015, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, azimilide hydrochloride; Bevacizumab, bortezomib, bosentan, buserelin; Caspofungin acetate, CC-4047, ChAGCD3, ciclesonide, clopidogrel, curcumin, Cypher; Dabigatran etexilate, dapoxetine hydrochloride, darbepoetin alfa, darusentan, denosumab, DMXB-Anabaseine, drospirenone, drospirenone/estradiol, duloxetine hydrochloride, dutasteride; Edodekin alfa, efaproxiral sodium, elaidic acid-cytarabine, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, eszopiclone, etonogestrel/testosterone decanoate, exenatide; Fulvestrant; Gefitinib, glycine, GVS-111; Homoharringtonine; ICC-1132, imatinib mesylate, iodine (I131) tositumomab, i.v. gamma-globulin; Levetiracetam, levocetirizine, lintuzumab, liposomal nystatin, lumiracoxib, lurtotecan; Manitimus, mapatumumab, melatonin, micafungin sodium, mycophenolic acid sodium salt; Oblimersen sodium, OGX-011, olmesartan medoxomil, omalizumab, omapatrilat, oral insulin; Parathyroid hormone (human recombinant), pasireotide, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, phVEGF-A165, pimecrolimus, pitavastatin calcium, plerixafor hydrochloride, posaconazole, pramlintide acetate, prasterone, pregabalin, PT-141; Quercetin; Ranolazine, rosuvastatin calcium, rubitecan, rupatadine fumarate; Sardomozide, sunitinib malate; Tadalafil, talactoferrin alfa, tegaserod maleate, telithromycin, testosterone transdermal patch, TH-9507, tigecycline, tiotropium bromide, tipifarnib, tocilizumab, treprostinil sodium; Valdecoxib, vandetanib

  9. Crystal structure of di-μ-chloro-acetato-hexa-kis-(di-methyl-formamide)-tetra-kis-(μ-N,2-dioxido-benzene-1-carboximidato)tetra-manganese(III)disodium dimethyl-formamide disolvate.

    PubMed

    Daly, Connor I; Zeller, Matthias; Zaleski, Curtis M

    2014-12-01

    The synthesis, crystal structure, and FT-IR data for the title compound, [Na2Mn4(C2H2ClO2)2(C7H4NO3)4(C3H7NO)6]·2C3H7NO or Na2(O2CCH2Cl)2[12-MCMn(III) N(shi)-4](DMF)6·2DMF, where MC is metallacrown, shi(3-) is salicyl-hydroximate, and DMF is N,N-di-methyl-formamide, is reported. The macrocyclic metallacrown consists of an -[Mn(III)-N-O]4- ring repeat unit and the metallacrown captures two Na(+) ions in the central cavity above and below the plane of the metallacrown. Each Na(+) ion is seven-coordinate and is bridged to two ring Mn(III) ions, through either a coordinating DMF mol-ecule or a chloro-acetate anion. The ring Mn(III) ions have either a tetra-gonally distorted octa-hedral geometry or a distorted square-pyramidal geometry. Weak C-H⋯O inter-actions, in addition to pure van der Waals forces, contribute to the overall packing of the mol-ecules. The complete molecule has inversion symmetry and is disordered over two sets of sites with an occupancy ratio of 0.8783 (7):0.1217 (7). The solvent molecule is also disordered over two sets of sites, with an occupancy ratio of 0.615 (5):0.385 (5). PMID:25552975

  10. Repetitive responses to nanoparticle albumin-bound paclitaxel and carboplatin in malignant pleural mesothelioma.

    PubMed

    Kanai, Osamu; Fujita, Kohei; Nakatani, Koichi; Mio, Tadashi

    2016-03-01

    Malignant pleural mesothelioma (MPM) is a rare tumor with a poor prognosis. Although cisplatin plus pemetrexed is the standard chemotherapy for patients with unresectable MPM, few agents are available for MPM patients who do not tolerate pemetrexed. Here, we report the first case of an MPM patient for whom the combination of nanoparticle albumin-bound paclitaxel and carboplatin (nabPC) repetitively achieved tumor regression. A 76-year-old man was diagnosed with epithelioid MPM. One cycle of carboplatin plus pemetrexed and two cycles of gemcitabine were administered but failed to inhibit tumor progression. By contrast, four cycles of nabPC resulted in a good response. Upon disease progression, four cycles of nabPC were performed again and resulted in a modest response. In conclusion, based on the present case, nabPC is a potential alternative chemotherapeutic agent for MPM, especially for MPM patients who do not tolerate pemetrexed. PMID:26839699

  11. 21 CFR 135.110 - Ice cream and frozen custard.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... treating the concentrated skim milk with calcium hydroxide and disodium phosphate; and whey and those... percent total milk solids are: Casein prepared by precipitation with gums, ammonium caseinate,...

  12. 21 CFR 135.110 - Ice cream and frozen custard.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... treating the concentrated skim milk with calcium hydroxide and disodium phosphate; and whey and those... percent total milk solids are: Casein prepared by precipitation with gums, ammonium caseinate,...

  13. 21 CFR 135.110 - Ice cream and frozen custard.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... treating the concentrated skim milk with calcium hydroxide and disodium phosphate; and whey and those... percent total milk solids are: Casein prepared by precipitation with gums, ammonium caseinate,...

  14. 21 CFR 135.110 - Ice cream and frozen custard.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... treating the concentrated skim milk with calcium hydroxide and disodium phosphate; and whey and those... percent total milk solids are: Casein prepared by precipitation with gums, ammonium caseinate,...

  15. 21 CFR 175.210 - Acrylate ester copolymer coating.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) The acrylate ester copolymer is a fully polymerized copolymer of ethyl acrylate, methyl methacrylate... emulsion defoamer. Disodium hydrogen phosphate Do. Formaldehyde Glyceryl monostearate Methyl...

  16. 21 CFR 175.210 - Acrylate ester copolymer coating.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) The acrylate ester copolymer is a fully polymerized copolymer of ethyl acrylate, methyl methacrylate... emulsion defoamer. Disodium hydrogen phosphate Do. Formaldehyde Glyceryl monostearate Methyl...

  17. 21 CFR 529.2464 - Ticarcillin powder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... powder. (a) Specifications. Each vial contains ticarcillin disodium equivalent to 6 grams of ticarcillin... grams per day, intrauterine, for 3 consecutive days during estrus. (2) Indications for use....

  18. Estimating the likelihood of sustained virological response in chronic hepatitis C therapy.

    PubMed

    Mauss, S; Hueppe, D; John, C; Goelz, J; Heyne, R; Moeller, B; Link, R; Teuber, G; Herrmann, A; Spelter, M; Wollschlaeger, S; Baumgarten, A; Simon, K-G; Dikopoulos, N; Witthoeft, T

    2011-04-01

    The likelihood of a sustained virological response (SVR) is the most important factor for physicians and patients in the decision to initiate and continue therapy for chronic hepatitis C (CHC) infection. This study identified predictive factors for SVR with peginterferon plus ribavirin (RBV) in patients with CHC treated under 'real-life' conditions. The study cohort consisted of patients from a large, retrospective German multicentre, observational study who had been treated with peginterferon alfa-2a plus RBV or peginterferon alfa-2b plus RBV between the years 2000 and 2007. To ensure comparability regarding peginterferon therapies, patients were analysed in pairs matched by several baseline variables. Univariate and multivariate logistic regression analyses were used to determine the effect of nonmatched baseline variables and treatment modality on SVR. Among 2378 patients (1189 matched pairs), SVR rates were 57.9% overall, 46.5% in HCV genotype 1/4-infected patients and 77.3% in genotype 2/3-infected patients. In multivariate logistic regression analysis, positive predictors of SVR were HCV genotype 2 infection, HCV genotype 3 infection, low baseline viral load and treatment with peginterferon alfa-2a. Negative predictors of SVR were higher age (≥40 years), elevated baseline gamma-glutamyl transpeptidase (GGT) and low baseline platelet count (<150,000/μL). Among patients treated with peginterferon plus RBV in routine clinical practice, genotype, baseline viral load, age, GGT level and platelet levels all predict the likelihood of treatment success. In patients matched by baseline characteristics, treatment with peginterferon alfa-2a may be a positive predictor of SVR when compared to peginterferon alfa-2b. PMID:20849436

  19. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-10-01

    Gateways to clinical trials is a guide to the most recent trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (+)-Dapoxetine hydrochloride, (S)-Tenatoprazole sodium salt monohydrate 19-28z, Acotiamide hydrochloride hydrate, ADV-TK, AE-37, Aflibercept, Albinterferon alfa-2b, Aliskiren fumarate, Asenapine maleate, Axitinib; Bavituximab, Becatecarin, beta-1,3/1,6-Glucan, Bevacizumab, Bremelanotide; Calcipotriol/betamethasone dipropionate, Casopitant mesylate, Catumaxomab, CDX-110, Cediranib, CMD-193, Cositecan; Darinaparsin, Denosumab, DP-b99, Duloxetine hydrochloride; E75, Ecogramostim, Elacytarabine, EMD-273063, EndoTAG-1, Enzastaurin hydrochloride, Eplerenone, Eribulin mesilate, Esomeprazole magnesium, Etravirine, Everolimus, Ezetimibe; Faropenem daloxate, Febuxostat, Fenretinide; Ghrelin (human); I-131 ch-TNT-1/B, I-131-3F8, Iclaprim, Iguratimod, Iloperidone, Imatinib mesylate, Inalimarev/Falimarev, Indacaterol, Ipilimumab, Iratumumab, Ispinesib mesylate, Ixabepilone; Lapatinib ditosylate, Laquinimod sodium, Larotaxel dehydrate, Linezolid, LOR-2040; Mapatumumab, MKC-1, Motesanib diphosphate, Mycophenolic acid sodium salt; NK-012; Olanzapine pamoate, Oncolytic HSV, Ortataxel; Paclitaxel nanoparticles, Paclitaxel poliglumex, Paliperidone palmitate, Panitumumab, Patupilone, PCV-9, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pertuzumab, Picoplatin, Pimavanserin tartrate, Pimecrolimus, Plerixafor hydrochloride, PM-02734, Poly I:CLC, PR1, Prasugrel, Pregabalin, Progesterone caproate, Prucalopride, Pumosetrag hydrochloride; RAV-12, RB-006, RB-007, Recombinant human erythropoietin alfa, Rimonabant, Romidepsin; SAR-109659, Satraplatin, Sodium butyrate; Tadalafil, Talampanel, Tanespimycin, Tarenflurbil, Tariquidar

  20. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2007-09-01

    12B75, 274150; Abacavir sulfate/lamivudine, Abatacept, Ad2/HIF-1alpha, Adalimumab, Adefovir, Adefovir dipivoxil, AGN-201904-Z, AIDSVAX, Albinterferon alfa-2b, Alemtuzumab, Aliskiren fumarate, Alvimopan hydrate, Amlodipine besylate/atorvastatin calcium, Amlodipine besylate/Olmesartan medoxomil, Ammonium tetrathiomolybdate, Amodiaquine, Apaziquone, Aprepitant, Arsenic trioxide, Artesunate/Amodiaquine, Ascorbic acid, Atazanavir sulfate, Atazanavir/ritonavir, Atomoxetine hydrochloride, Atrigel-Leuprolide, Axitinib; Bevacizumab, Binodenoson, Bortezomib, Bovine lactoferrin; Calcipotriol/betamethasone dipropionate, Carisbamate, Certolizumab pegol, Ciclesonide, Conivaptan hydrochloride, CP-690550, CP-751871, Cypher; Dapivirine, Darbepoetin alfa, Darunavir, Dasatinib, del-1 Genemedicine, Denosumab, Desloratadine, Dexlansoprazole, DiabeCell, Drospirenone/ethinylestradiol, DTaP-HepB-IPV, Duloxetine hydrochloride, Dutasteride; Eculizumab, Eldecalcitol, Eletriptan, Emtricitabine, Entecavir, Eritoran tetrasodium, Ertapenem sodium, Escitalopram oxalate, Eslicarbazepine acetate, Esomeprazole magnesium, Estradiol acetate, Eszopiclone, ETEC vaccine, Etoricoxib, Exenatide, Ezetimibe; Fluticasone furoate, Fosmidomycin, Fosmidomycin/clindamycin; Glutamine; Heat Shock Protein 10, Hepatitis B hyperimmunoglobulin, HIV vaccine, Hochuekki-to, Human Albumin, Human papillomavirus vaccine; Immune globulin subcutaneous [human], IMP-321, Interferon omega, ISIS-301012, Istaroxime; Japanese encephalitis virus vaccine; Latanoprost/timolol maleate, Lenalidomide, Linaclotide acetate, Lumiracoxib, LY-517717; Malaria vaccine, MAS-063D, Meningitis B vaccine, Mepolizumab, Methylnaltrexone bromide, Micafungin sodium, MK-0822A, Morphine glucuronide, Morphine hydrochloride, Mycophenolic acid sodium salt; Natalizumab, Nesiritide, Norelgestromin/ethinyl estradiol, NT-201; Oblimersen sodium, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide, Omalizumab, Otamixaban; Paclitaxel nanoparticles

  1. 40 CFR 721.9795 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[(4,6-dichloro-1,3,5-triazin-2-yl) amino...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Benzenesulfonic acid, 2,2â²-(1,2... Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with dialkyl amines (generic). (a... generically as a benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with...

  2. 21 CFR 74.203 - FD&C Green No. 3.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-aminobenzenesulfonic acid) to sodium 5-amino-2-formylbenzenesulfonate. This amine is diazotized and the resulting...&C Green No. 3 is principally the inner salt disodium salt of N-ethyl-N- amino]phenyl](4-hydroxy-2...-45-9); with smaller amounts of the isomeric inner salt disodium salt of N-ethyl-N-...

  3. 40 CFR 721.9795 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[(4,6-dichloro-1,3,5-triazin-2-yl) amino...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Benzenesulfonic acid, 2,2â²-(1,2... Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with dialkyl amines (generic). (a... generically as a benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with...

  4. 40 CFR 721.9795 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[(4,6-dichloro-1,3,5-triazin-2-yl) amino...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Benzenesulfonic acid, 2,2â²-(1,2... Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with dialkyl amines (generic). (a... generically as a benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with...

  5. 21 CFR 74.203 - FD&C Green No. 3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-aminobenzenesulfonic acid) to sodium 5-amino-2-formylbenzenesulfonate. This amine is diazotized and the resulting...&C Green No. 3 is principally the inner salt disodium salt of N-ethyl-N- amino]phenyl](4-hydroxy-2...-45-9); with smaller amounts of the isomeric inner salt disodium salt of N-ethyl-N-...

  6. 76 FR 25234 - Listing of Color Additives Exempt From Certification; Reactive Blue 69

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-04

    ... of disodium 1-amino-4- -2-sulphonatophenyl]amino]-9,10-dihydro- 9,10-dioxoanthracene-2-sulphonate... November 18, 2009 (74 FR 59560), FDA announced that a color additive petition (CAP 8C0287) had been filed... Devices, to provide for the safe use of disodium 1- amino-4- -2-sulphonatophenyl]amino]-9,10-...

  7. Crystal structure of the inverse crown ether tetra­kis­[μ2-bis­(tri­methyl­sil­yl)amido]-μ4-oxido-dicobalt(II)disodium, [Co2Na2{μ2-N(SiMe3)2}4](μ4-O)

    PubMed Central

    Hansen, Christopher B.; Filatov, Alexander S.; Hillhouse, Gregory L.

    2016-01-01

    The title compound, [Co2Na2{μ2-N(SiMe3)2}4](μ4-O), (I), represents a new entry in the class of inverse crown ethers. In the mol­ecule, each Co atom is formally in the oxidation state +II. The structure contains one half of a unique mol­ecule per asymmetric unit with the central μ4-oxido ligand residing on an inversion center, leading to a planar coordination to the Na and Co atoms. In the crystal, bulky tri­methyl­silyl substituents prevent additional inter­actions with cobalt. However, weak inter­molecular Na⋯H3C—Si inter­actions form an infinite chain along [010]. The structure is isotypic with its Mg, Mn and Zn analogues. PMID:27308041

  8. Crystal structure of the inverse crown ether tetra-kis-[μ2-bis-(tri-methyl-sil-yl)amido]-μ4-oxido-dicobalt(II)disodium, [Co2Na2{μ2-N(SiMe3)2}4](μ4-O).

    PubMed

    Hansen, Christopher B; Filatov, Alexander S; Hillhouse, Gregory L

    2016-06-01

    The title compound, [Co2Na2{μ2-N(SiMe3)2}4](μ4-O), (I), represents a new entry in the class of inverse crown ethers. In the mol-ecule, each Co atom is formally in the oxidation state +II. The structure contains one half of a unique mol-ecule per asymmetric unit with the central μ4-oxido ligand residing on an inversion center, leading to a planar coordination to the Na and Co atoms. In the crystal, bulky tri-methyl-silyl substituents prevent additional inter-actions with cobalt. However, weak inter-molecular Na⋯H3C-Si inter-actions form an infinite chain along [010]. The structure is isotypic with its Mg, Mn and Zn analogues. PMID:27308041

  9. Crystal structure of di-μ-chloro­acetato-hexa­kis­(di­methyl­formamide)­tetra­kis­(μ-N,2-dioxido­benzene-1-carboximidato)tetra­manganese(III)disodium dimethyl­formamide disolvate

    PubMed Central

    Daly, Connor I.; Zeller, Matthias; Zaleski, Curtis M.

    2014-01-01

    The synthesis, crystal structure, and FT–IR data for the title compound, [Na2Mn4(C2H2ClO2)2(C7H4NO3)4(C3H7NO)6]·2C3H7NO or Na2(O2CCH2Cl)2[12-MCMnIII N(shi)-4](DMF)6·2DMF, where MC is metallacrown, shi3− is salicyl­hydroximate, and DMF is N,N-di­methyl­formamide, is reported. The macrocyclic metallacrown consists of an –[MnIII—N—O]4– ring repeat unit and the metallacrown captures two Na+ ions in the central cavity above and below the plane of the metallacrown. Each Na+ ion is seven-coordinate and is bridged to two ring MnIII ions, through either a coordinating DMF mol­ecule or a chloro­acetate anion. The ring MnIII ions have either a tetra­gonally distorted octa­hedral geometry or a distorted square-pyramidal geometry. Weak C—H⋯O inter­actions, in addition to pure van der Waals forces, contribute to the overall packing of the mol­ecules. The complete molecule has inversion symmetry and is disordered over two sets of sites with an occupancy ratio of 0.8783 (7):0.1217 (7). The solvent molecule is also disordered over two sets of sites, with an occupancy ratio of 0.615 (5):0.385 (5). PMID:25552975

  10. Sodium carbonate poisoning

    MedlinePlus

    Sal soda poisoning; Soda ash poisoning; Disodium salt poisoning; Carbonic acid poisoning; Washing soda poisoning ... have symptoms. In this rare situation, long-term effects, even death, are possible if you do not ...

  11. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate. Magnesium stearate....

  12. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...: Aluminum mono-, di-, and tristearate. Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate....

  13. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...: Aluminum mono-, di-, and tristearate. Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate....

  14. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...: Aluminum mono-, di-, and tristearate. Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate....

  15. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...: Aluminum mono-, di-, and tristearate. Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate....

  16. 21 CFR 529.2464 - Ticarcillin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) Specifications. Each vial contains ticarcillin disodium powder equivalent to 6 grams of ticarcillin for... 6 grams daily by intrauterine infusion for 3 consecutive days during estrus. (2) Indications for...

  17. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-03-01

    , mycophenolate mofetil, mycophenolic acid sodium salt; Nitisinone; Omalizumab, omapatrilat, ONYX-015, oxaliplatin; Paclitaxel, paclitaxel nanoparticles, panitumumab, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pertuzumab, phosphatidylcholine-rich phospholipid mixture, pimecrolimus, pioglitazone hydrochloride, pramlintide acetate, prasterone; QR-333; Ranelic acid distrontium salt, ranolazine, rasagiline mesilate, RFB4(dsFv)-PE38, ribavirin, rifabutin, risperidone, rituximab, rofecoxib, rosiglitazone maleate, rosiglitazone maleate/metformin hydrochloride, rotavirus vaccine; S-236, salmeterol xinafoate, sarizotan hydrochloride, sildenafil, sildenafil citrate, sunitinib malate; Tadalafil, tegaserod maleate, temozolomide, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, trabectedin, treprostinil sodium; Vandetanib, vardenafil hydrochloride hydrate, vatalanib succinate, vinflunine, virosome influenza vaccine, voriconazole; Zidovudine. PMID:16636723

  18. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-01-01

    4; NBI-56418, NCX-4016, nesiritide, nicotine conjugate vaccine, NSC-330507; Oglufanide, omalizumab, oxipurinol; Palifermin, palonosetron hydrochloride, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, PEGylated interferon alfacon-1, perospirone hydrochloride, pimecrolimus, pixantrone maleate, plerixafor hydrochloride, PowderJect lidocaine, pradefovir mesylate, prasterone, pregabalin, Prostvac VF, PT-141, PTC-124, pyridoxamine; QS-21, quercetin; R-126638, R-411, ralfinamide, rasagiline mesilate, rF-PSA, RG-2077, rhThrombin, rimonabant hydrochloride, rofecoxib, rosuvastatin calcium, rotigotine hydrochloride, rV-PSA; S-18886, S-303, seocalcitol, SGN-40, sitaxsentan sodium, SPP-301, St. John's Wort extract; Tadalafil, taxus, telithromycin, tenatoprazole, tenofovir disoproxil fumarate, testosterone MDTS, testosterone transdermal patch, tgAAC-09, TH-9507, thioacetazone, tipifarnib, TQ-1011, trabectedin, travoprost, trimethoprim; Valdecoxib, valganciclovir hydrochloride, valopicitabine, voriconazole; Xcellerated T cells. PMID:16179960

  19. Collaborative study for the validation of an improved HPLC assay for recombinant IFN-alfa-2.

    PubMed

    Jönsson, K H; Daas, A; Buchheit, K H; Terao, E

    2016-01-01

    The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2 include a nonspecific photometric protein assay using albumin as calibrator and a highly variable cell-based assay for the potency determination of the protective effects. A request was expressed by the Official Medicines Control Laboratories (OMCLs) for improved methods for the batch control of recombinant interferon alfa-2 bulk and market surveillance testing of finished products, including those formulated with Human Serum Albumin (HSA). A HPLC method was developed at the Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An initial collaborative study run under the Biological Standardisation Programme (BSP; study code BSP039) revealed the need for minor changes to improve linearity of the calibration curves, assay reproducibility and robustness. The goal of the collaborative study, coded BSP071, was to transfer and further validate this improved HPLC method. Ten laboratories participated in the study. Four marketed IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference standards from two manufacturers were used for the quantitative assay. The modified method was successfully transferred to all laboratories despite local variation in equipment. The resolution between the main and the oxidised forms of IFN-alfa-2 was improved compared to the results from the BSP039 study. The improved method even allowed partial resolution of an extra peak after the principal peak. Symmetry of the main IFN peak was acceptable for all samples in all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the origin and coefficients of determination greater than 0.9995. Assay repeatability, intermediate precision and reproducibility varied with the tested sample within acceptable

  20. Alternative to Ph. Eur. pour-plate method for detection of microbial contamination in non-sterile pharmaceutical preparations.

    PubMed

    Palicz, A; Paul, A; Hofmann, A; Denzel, K

    2016-01-01

    The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2 include a nonspecific photometric protein assay using albumin as calibrator and a highly variable cell-based assay for the potency determination of the protective effects. A request was expressed by the Official Medicines Control Laboratories (OMCLs) for improved methods for the batch control of recombinant interferon alfa-2 bulk and market surveillance testing of finished products, including those formulated with Human Serum Albumin (HSA). A HPLC method was developed at the Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An initial collaborative study run under the Biological Standardisation Programme (BSP; study code BSP039) revealed the need for minor changes to improve linearity of the calibration curves, assay reproducibility and robustness. The goal of the collaborative study, coded BSP071, was to transfer and further validate this improved HPLC method. Ten laboratories participated in the study. Four marketed IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference standards from two manufacturers were used for the quantitative assay. The modified method was successfully transferred to all laboratories despite local variation in equipment. The resolution between the main and the oxidised forms of IFN-alfa-2 was improved compared to the results from the BSP039 study. The improved method even allowed partial resolution of an extra peak after the principal peak. Symmetry of the main IFN peak was acceptable for all samples in all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the origin and coefficients of determination greater than 0.9995. Assay repeatability, intermediate precision and reproducibility varied with the tested sample within acceptable

  1. Application of Novel Nonlinear Optical Materials to Optical Processing

    NASA Technical Reports Server (NTRS)

    Banerjee, Partha P.

    1999-01-01

    We describe wave mixing and interactions in nonlinear photorefractive polymers and disodium flourescein. Higher diffracted orders yielding forward phase conjugation can be generated in a two-wave mixing geometry in photorefractive polymers, and this higher order can be used for image edge enhancement and correlation. Four-wave mixing and phase conjugation is studied using nonlinear disodium floureschein, and the nature and properties of gratings written in this material are investigated.

  2. 40 CFR 721.9790 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-[bis(2-hydroxypropyl) amino]- 6-[(3...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-ethenediyl)bis - 6- -1,3,5-triazin-2-yl]amino]-, disodium salt, compd. with 2,2â²,2â³-nitrilo-tris (1:2); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6- -1,3,5-triazin-2-yl]amino]-2-sulfophenyl]ethenyl...-ethenediyl)bis - 6- -1,3,5-triazin-2-yl]amino]-, disodium salt, compd. with......

  3. 40 CFR 721.1660 - Benzidine-based chemical substances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...- -, disodium salt 6358-80-1 C.I. Acid Black 94 30336 2,7-Naphthalenedisulfonic acid, 4-amino-5- hydroxy-3... number C.I. name C.I. number Chemical Name 92-87-5 Benzidine 0N/A -4,4′-diamine 531-85-1 Benzidine · 2HCL...-Naphthalenedisulfonic acid, 4-amino-3- -4-yl]azo]-5-hydroxy-6-(phenylazo)-, disodium salt 2302-97-8 C.I. Direct Red...

  4. 40 CFR 721.1660 - Benzidine-based chemical substances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...- -, disodium salt 6358-80-1 C.I. Acid Black 94 30336 2,7-Naphthalenedisulfonic acid, 4-amino-5- hydroxy-3... number C.I. name C.I. number Chemical Name 92-87-5 Benzidine 0N/A -4,4′-diamine 531-85-1 Benzidine · 2HCL...-Naphthalenedisulfonic acid, 4-amino-3- -4-yl]azo]-5-hydroxy-6-(phenylazo)-, disodium salt 2302-97-8 C.I. Direct Red...

  5. 40 CFR 721.9790 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-[bis(2-hydroxypropyl) amino]- 6-[(3...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-ethenediyl)bis - 6- -1,3,5-triazin-2-yl]amino]-, disodium salt, compd. with 2,2â²,2â³-nitrilo-tris (1:2); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6- -1,3,5-triazin-2-yl]amino]-2-sulfophenyl]ethenyl...-ethenediyl)bis - 6- -1,3,5-triazin-2-yl]amino]-, disodium salt, compd. with......

  6. Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase Glomerulonephritis.

    PubMed

    Gan, Poh-Yi; O'Sullivan, Kim M; Ooi, Joshua D; Alikhan, Maliha A; Odobasic, Dragana; Summers, Shaun A; Kitching, A Richard; Holdsworth, Stephen R

    2016-05-01

    Observations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium, which correlated with the severity of tubulointerstitial injury. Furthermore, most of the mast cells were degranulated and spindle-shaped in patients with acute AAV, indicating an activated phenotype. We hypothesized that the mast cell stabilizer disodium cromoglycate would attenuate mast cell degranulation without affecting IL-10 production. We induced anti-MPO GN by immunizing mice with MPO and a low dose of anti-glomerular basement membrane antibody. When administered before or after induction of MPO autoimmunity in these mice, disodium cromoglycate attenuated mast cell degranulation, development of autoimmunity, and development of GN, without diminishing IL-10 production. In contrast, administration of disodium cromoglycate to mast cell-deficient mice had no effect on the development of MPO autoimmunity or GN. MPO-specific CD4(+) effector T cell proliferation was enhanced by co-culture with mast cells, but in the presence of disodium cromoglycate, proliferation was inhibited and IL-10 production was enhanced. These results indicate that disodium cromoglycate blocks injurious mast cell degranulation specifically without affecting the immunomodulatory role of these cells. Thus as a therapeutic, disodium cromoglycate may substantially enhance the regulatory role of mast cells in MPO-AAV. PMID:26374606

  7. Immunotherapy with imiquimod and interferon alfa for metastasized Merkel cell carcinoma

    PubMed Central

    Wahl, R.U.; Braunschweig, T.; Ghassemi, A.; Rübben, A.

    2016-01-01

    Merkel cell carcinoma (mcc) is a highly aggressive neuroendocrine tumour of the skin. Remission rates are high with chemotherapy in patients with metastasis, but without any improvement in overall survival. We present the case of a 90-year-old woman with facial mcc. After radiation and surgery, the mcc recurred with widespread cutaneous and regional lymph node metastases. The metastases were treated with weekly intralesional injections of 1–2×106 IU interferon alfa-2a, accompanied by topical imiquimod 5% cream 3 times weekly. After partial regression, subcutaneous pegylated interferon alfa-2b was added at a dose of 30 μg weekly, which was then increased to 50 μg weekly. At 4 months after the start of immunotherapy, all cutaneous metastases and the intralesionally treated lymph node metastases receded. Interruption or reduction of systemic interferon application resulted in locoregional relapses that were successfully treated with surgery or intralesional interferon injections. The patient remains alive 30 months after initiation of immunotherapy, suggesting that locally metastasized mcc might be able to be controlled with local and systemic immunotherapy. PMID:27122984

  8. Cutaneous melanoma: new advances in treatment*

    PubMed Central

    Foletto, Michele Ceolin; Haas, Sandra Elisa

    2014-01-01

    Cutaneous melanoma is a challenge to treat. Over the last 30 years, no drug or combination of drugs demonstrated significant impact to improve patient survival. From 1995 to 2000, the use of cytokines such as interferon and interleukin become treatment options. In 2011, new drugs were approved by the U.S. Food and Drug Administration, including peginterferon alfa-2b for patients with stage III disease, vemurafenib for patients with metastatic melanoma with the BRAF V600E mutation, and ipilimumab, a monoclonal antibody directed to the CTLA-4 T lymphocyte receptor, to combat metastatic melanoma in patients who do not have the BRAF V600E mutation. Both ipilimumab and vemurafenib showed results in terms of overall survival. Other trials with inhibitors of other genes, such as the KIT gene and MEK, are underway in the search for new discoveries. The discovery of new treatments for advanced or metastatic disease aims to relieve symptoms and improve patient quality of life. PMID:24770508

  9. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-11-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, adalimumab, adefovir dipivoxil, AdGVVEGF121.10, anastrozole, anecortave acetate, aripiprazole, asulacrine isethionate, atazanavir, ATL-962, 16-Aza-epothilone B; Bevacizumab, bicalutamide, blonanserin, BMS-188667, bosentan; Celecoxib, celmoleukin, cetuximab, cilomilast, cinacalcet hydrochloride, CNTF(Ax15), colesevelam hydrochloride; Daclizumab, delavirdine mesilate, desogestrel, desoxyepothilone B, dexmethylphenidate hydrochloride, duloxetine hydrochloride; Ecogramostim, emtricitabine, epalrestat, escitalopram oxalate, examorelin, exendin-4, ezetimibe; Fidarestat, frovatriptan; HIV-1 Immunogen; Iloperidone, insulin detemir, insulin lispro, irinotecan hydrochloride; Keratinocyte growth factor; Lasofoxifene tartrate, levetiracetam, levormeloxifene, levosimendan, lumiracoxib, LY-307161 SR; Memantine hydrochloride, MEN-10755, metformin hydrochloride, metreleptin, motexafin gadolinium; Naratriptan hydrochloride, natalizumab, nesiritide, nicotine, NN-2211, NN-414; Olanzapine, omalizumab; Pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pimecrolimus, pirfenidone, pramlintide acetate prasterone, pregabalin; Quetiapine fumarate; Rabeprazole sodium, raloxifene hydrochloride, raltitrexed, rDNA insulin, rFGF-2, risedronate sodium, rofecoxib, roflumilast, rosiglitazone maleate; SN-22995; Tacrolimus, tadalafil, tegaserod maleate, tiotropium bromide, tomoxetine hydrochloride, trastuzumab, trimegestone; Voglibose, Voriconazole; Ziprasidone hydrochloride. PMID:12616707

  10. Perspectives on dual hepatitis B and C infection in Taiwan.

    PubMed

    Liu, Chun-Jen; Chen, Pei-Jer; Chen, Ding-Shinn; Tseng, Tai-Chung; Kao, Jia-Horng

    2016-05-01

    Dual hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is not rare in HBV or HCV endemic areas, and can be found in populations at risk of parenteral viral transmission. Clinical observatory studies suggest a higher risk of liver disease progression in patients with dual HCV/HBV infection than in HBV or HCV monoinfected patients. Recent trials confirmed that combination therapy of peginterferon alfa-2a or alfa-2b and ribavirin was effective and safe in dually infected patients with positive HCV RNA. Moreover, about 30% of the dually infected patients cleared hepatitis B surface antigen within 5 years after the start of peginterferon-based therapy. The optimal treatment strategies for dually infected patients with active hepatitis B, with decompensated cirrhosis, or in other clinical situations should be explored in further studies. Finally, the advent of new direct-acting antiviral-based anti-HCV therapy may lead to the development of strategies for the treatment of dually infected patients with active hepatitis C, particularly for those not tolerating or not eligible for peginterferon-based therapy. Notably, direct-acting antivirals would not have any activity against HBV infection; simultaneous or on-demand nucleos(t)ide analogs would be needed if clinically indicated. PMID:26188762

  11. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in the current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV-NGFbeta, aprepitant, aripiprazole, atomoxetine hydrochloride; beta-Methyl-6-chloromelatonin, BMS-214662, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, CEA-TRICOM, cetuximab, ciclesonide, clofarabine, Cypher; Dalbavancin, darbepoetin alfa, darifenacin hydrobromide, desloratadine, Dexamet, drospirenone, drospirenone/ethinylestradiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, ertapenem sodium, escitalopram oxalate, eszopiclone; Fenretinide; Gefitinib, gestodene, ghrelin (human); hMaxi-K, human papillomavirus vaccine; Imatinib mesylate, indiplon, iodine (i131) tositumomab, irofulven, ISS-1018; Lasofoxifene tartrate, levodopa/carbidopa/entacapone, liposomal doxorubicin; Nemifitide ditriflutate, nesiritide; Omalizumab; Pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, phVEGF-A165, pimecrolimus, pramlintide acetate; Rasburicase, rimonabant hydrochloride; Satraplatin, St. John's Wort extract, sunitinib malate; Tadalafil, tanaproget, Taxus, tiotropium bromide, treprostinil sodium; Valdecoxib, vardenafil hydrochloride hydrate; Ximelagatran; Zileuton. PMID:16258596

  12. Patient education improves adherence to peg-interferon and ribavirin in chronic genotype 2 or 3 hepatitis C virus infection: A prospective, real-life, observational study

    PubMed Central

    Cacoub, Patrice; Ouzan, Denis; Melin, Pascal; Lang, Jean-Philippe; Rotily, Michel; Fontanges, Thierry; Varastet, Marina; Chousterman, Michel; Marcellin, Patrick

    2008-01-01

    AIM: To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response (SVR) in a real-life setting in genotype 2/3 hepatitis C, as there are few adherence data in genotype 2/3 infection, even from randomized trials. METHODS: This prospective survey included genotype 2/3 patients who received peg-interferon alfa-2b and ribavirin. There was no intervention. Adherence was self-reported over the past 4 wk (peg-interferon) or 7 d (ribavirin). Adherence to bitherapy was defined as adherence to the two drugs for ≥ 20 wk. SVR was defined as undetectable RNA ≥ 12wk after the end of treatment. RESULTS: 370/674 patients received education during the first 3 mo of treatment. After 6 mo, adherence to bitherapy was higher in educated patients (61% vs 47%, P = 0.01). Adherence to peg-interferon was 78% vs 69% (P = 0.06). Adherence to ribavirin was 70% vs 56% (P = 0.006). The SVR (77% vs 70%, P = 0.05) and relapse (10% vs 16%, P = 0.09) rates tended to be improved. After adjustment for baseline differences, education improved adherence [Odds ratio (OR) 1.58, P = 0.04] but not the SVR (OR 1.54, P = 0.06). CONCLUSION: In genotype 2/3 patients, therapeutic education helped maintain real-life adherence to bitherapy. PMID:18985810

  13. Immunotherapy with imiquimod and interferon alfa for metastasized Merkel cell carcinoma.

    PubMed

    Wahl, R U; Braunschweig, T; Ghassemi, A; Rübben, A

    2016-04-01

    Merkel cell carcinoma (mcc) is a highly aggressive neuroendocrine tumour of the skin. Remission rates are high with chemotherapy in patients with metastasis, but without any improvement in overall survival. We present the case of a 90-year-old woman with facial mcc. After radiation and surgery, the mcc recurred with widespread cutaneous and regional lymph node metastases. The metastases were treated with weekly intralesional injections of 1-2×10(6) IU interferon alfa-2a, accompanied by topical imiquimod 5% cream 3 times weekly. After partial regression, subcutaneous pegylated interferon alfa-2b was added at a dose of 30 μg weekly, which was then increased to 50 μg weekly. At 4 months after the start of immunotherapy, all cutaneous metastases and the intralesionally treated lymph node metastases receded. Interruption or reduction of systemic interferon application resulted in locoregional relapses that were successfully treated with surgery or intralesional interferon injections. The patient remains alive 30 months after initiation of immunotherapy, suggesting that locally metastasized mcc might be able to be controlled with local and systemic immunotherapy. PMID:27122984

  14. Treatment of refractory low grade lymphoma with chlorambucil alternating with interferon and radiotherapy.

    PubMed

    Avilés, A; Talavera, A; Guzmán, R; Cuadra, I

    1995-01-01

    We report the results of a clinical trial of chlorambucil (CB) alternating with interferon alfa 2b (IFN) in previously treated patients with low-grade lymphoma who were refractory to previous treatment. Patients received CB 10 mg/m2, po, daily, days 1-14, alternating with IFN 5.0 MU three times a week days 15-28 (six doses) by six monthly cycles. If partial response was achieved, patients received extended field radiotherapy to sites of nodal residual postchemotherapy disease. Forty-three patients were enrolled into the study, and 30 were evaluable for response and toxicity. Nineteen out of 39 (40%) achieved complete remission and 14 out of 39 (35%) had partial remission, thus the overall response was observed in 83% of the cases. Ten patients with partial response and residual nodal disease received radiotherapy and achieved complete response criteria. The median duration of response has not been achieved, yet, 23 patients remain in complete response after a median follow-up of 98.5 months. Toxicity was mild and 95% of the patients received the planned dose of CB and IFN. These results suggest that combination of CB and IFN and addition of radiotherapy to residual postchemotherapy nodal disease may be effective in patients with low-grade lymphoma without excessive toxicity and adequate quality of life. PMID:8590892

  15. Antibody-mediated pure red cell aplasia due to epoetin alfa during antiviral therapy of chronic hepatitis C.

    PubMed

    Stravitz, R Todd; Chung, Harold; Sterling, Richard K; Luketic, Velimir A; Sanyal, Arun J; Price, Angie S; Purrington, Amy; Shiffman, Mitchell L

    2005-06-01

    Anemia frequently complicates the treatment of chronic hepatitis C with interferon and ribavirin (RVN), requiring dose reduction and jeopardizing sustained virologic response. Increasingly, epoetin alfa is used to prevent anemia in this setting. Below, we report the first case of pure red cell aplasia (PRCA) in a patient with chronic hepatitis C who received epoetin alfa (Procrit) to manage anti-viral treatment-induced anemia. Red blood cell transfusion-dependence developed 16 wk after the patient was started on peginterferon alfa-2b and RVN for chronic hepatitis C despite the simultaneous administration of epoetin alfa and subsequent discontinuation of the antiviral medications. Bone marrow biopsy was consistent with PRCA. High-titer erythropoietin antibodies, assayed by two methods, appeared shortly after epoetin alfa was administered, and were associated with a decline in serum erythropoietin to undetectable levels. Erythropoietin antibodies directed toward epoetin alfa were shown to cross react with darbepoetin alfa (Aranesp), and a neutralization assay confirmed that they inhibited cell growth in the presence of erythropoietin. Transfusion-dependence resolved approximately 16 wk after discontinuing epoetin alfa, and 6 wk after starting danazol. PRCA caused by the development of erythropoietin antibodies is a potentially life-threatening complication of administering epoetin alfa to prevent the anemia associated with antiviral therapy in patients with chronic hepatitis C. PMID:15929778

  16. Novel Approaches to Treatment of Advanced Melanoma: A Review on Targeted Therapy and Immunotherapy.

    PubMed

    Niezgoda, Anna; Niezgoda, Piotr; Czajkowski, Rafał

    2015-01-01

    The incidence of malignant melanoma is increasing. The majority of patients are diagnosed in early stages when the disease is highly curable. However, the more advanced or metastatic cases have always been a challenge for clinicians. The poor prognosis for patients with melanoma is now changing as numerous of promising approaches have appeared recently. The discovery of aberrations of pathways responsible for intracellular signal transduction allowed us to introduce agents specifically targeting the mutated cascades. Numerous clinical studies have been conducted to improve effectiveness of melanoma treatment. From 2011 until now, the U.S. FDA has approved seven novel agents, such as BRAF-inhibitors (vemurafenib 2011, dabrafenib 2013), MEK-inhibitors (trametinib 2013), anti-PD1 antibodies (nivolumab 2014, pembrolizumab 2014), anti-CTLA-4 antibody (ipilimumab 2011), or peginterferon-alfa-2b (2011) intended to be used in most advanced cases of melanoma. Nevertheless, clinicians continue working on new possible methods of treatment as resistance to the novel drugs is a commonly observed problem. This paper is based on latest data published until the end of January 2015. PMID:26171394

  17. Novel Approaches to Treatment of Advanced Melanoma: A Review on Targeted Therapy and Immunotherapy

    PubMed Central

    Niezgoda, Anna; Niezgoda, Piotr; Czajkowski, Rafał

    2015-01-01

    The incidence of malignant melanoma is increasing. The majority of patients are diagnosed in early stages when the disease is highly curable. However, the more advanced or metastatic cases have always been a challenge for clinicians. The poor prognosis for patients with melanoma is now changing as numerous of promising approaches have appeared recently. The discovery of aberrations of pathways responsible for intracellular signal transduction allowed us to introduce agents specifically targeting the mutated cascades. Numerous clinical studies have been conducted to improve effectiveness of melanoma treatment. From 2011 until now, the U.S. FDA has approved seven novel agents, such as BRAF-inhibitors (vemurafenib 2011, dabrafenib 2013), MEK-inhibitors (trametinib 2013), anti-PD1 antibodies (nivolumab 2014, pembrolizumab 2014), anti-CTLA-4 antibody (ipilimumab 2011), or peginterferon-alfa-2b (2011) intended to be used in most advanced cases of melanoma. Nevertheless, clinicians continue working on new possible methods of treatment as resistance to the novel drugs is a commonly observed problem. This paper is based on latest data published until the end of January 2015. PMID:26171394

  18. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, adalimumab, AERx morphine sulphate, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, almotriptan, amprenavir, aripiprazole, atenolol, atorvastatin calcium; BSYX-A110; Cantuzumab mertansine, capravirine, CDP-571, CDP-870, celecoxib; Delavirdine mesilate, docetaxel, dofetilide, donepezil hydrochloride, duloxetine hydrochloride, dutasteride, dydrogesterone; Efavirenz, emtricitabine, enjuvia, enteryx, epristeride, erlotinib hydrochloride, escitalopram oxalate, etanercept, etonogestrel, etoricoxib; Fesoterodine, finasteride, flt3ligand; Galantamine hydrobromide, gemtuzumab ozogamicin, genistein, gepirone hydrochloride; Indinavir sulfate, infliximab; Lamivudine, lamivudine/zidovudine/abacavir sulfate, leteprinim potassium, levetiracetam, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, losartan potassium; MCC-465, MRA; Nebivolol, nesiritide, nevirapine; Olanzapine, OROS(R)-Methylphenidate hydrochloride; Peginterferon alfa-2a, peginterferon alfa-2b, Pimecrolimus, polyethylene glycol 3350, pramlintide acetate, pregabalin, PRO-2000; Risedronate sodium, risperidone, ritonavir, rituximab, rivastigmine tartrate, rofecoxib, rosuvastatin calcium; Saquinavir mesilate, Stavudine; Tacrolimus, tadalafil, tamsulosin hydrochloride, telmisartan, tomoxetine hydrochloride, treprostinil sodium, trimegestone, trimetrexate; Valdecoxib, venlafaxine hydrochloride; Zoledronic acid monohydrate. PMID:12616965

  19. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-04-01

    Gateways to clinical trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 5A8; Agomelatine, alefacept, almotriptan, anakinra, APC-8015, atazanavir, atomoxetine hydrochloride, azimilide hydrochloride; Bicifadine; Cannabidiol, caspofungin acetate, CAT-213, CGP-51901, ciclesonide, cipamfylline; Darbepoetin alfa, desloratadine, dibotermin alfa, DX-9065a; Ecogramostim, efalizumab, eletriptan, eniluracil, EPI-KAL2, erlosamide, ertapenem sodium, etilevodopa, etoricoxib, ezetimibe; Fosamprenavir calcium, fosamprenavir sodium, fumagillin; Gadofosveset sodium, gefitinib, gemtuzumab ozogamicin; HSPPC-96, human papillomavirus vaccine; Icatibant Id-KLH, imatinib mesylate, INS-37217, iodine (I131) tositumomab; LAS-34475, levobupivacaine hydrochloride, levocetirizine, linezolid, 131I-lipiodol, lonafarnib, lopinavir, LY-450108; Magnetites, MBI-594AN, melagatran, melatonin, mepolizumab, mycophenolic acid sodium salt; NC-100100; 1-Octanol, omalizumab, omapatrilat, onercept; PEG-filgrastim, (PE)HRG21, peginterferon alfa-2a, peginterferon alfa-2b, pleconaril, pneumococcal 7-valent conjugate vaccine, prasterone; Ranelic acid distrontium salt, rasagiline mesilate, reslizumab, rFGF-2, rhOP-1, rosuvastatin calcium, roxifiban acetate; Sitaxsentan sodium, sodium lauryl sulfate; Tadalafil, telithromycin, tenofovir disoproxil fumarate, tipranavir, TMC-114, tucaresol; Valdecoxib, voriconazole; Ximelagatran; Zofenopril calcium, zosuquidar trihydrochloride. PMID:12743628

  20. Exemestane blocks mesothelioma growth through downregulation of cAMP, pCREB and CD44 implicating new treatment option in patients affected by this disease

    PubMed Central

    2014-01-01

    Background Recent evidence suggests that aromatase may be involved in the pathogenesis of malignant mesothelioma. Here, we evaluated the effect of exemestane, an inhibitor of aromatase, in the treatment of mesothelioma using in vitro and in vivo preclinical models. Results We show a significant reduction of cell proliferation, survival, migration and block of cells in S phase of cell cycle in mesothelioma cells upon exemestane treatment. Moreover, we find that CD44, which is involved in mesothelioma cells migration, was modulated by exemestane via cAMP and pCREB. Most importantly, in mice mesothelioma xenograft exemestane causes a significant decrease in tumor size and the association pemetrexed/exemestane is more effective than pemetrexed/cisplatin. Conclusion The preclinical mesothelioma model suggests that exemestane might be beneficial in mesothelioma treatment. PMID:24655565

  1. [Maintenance therapy for advanced non-small-cell lung cancer].

    PubMed

    Saruwatari, Koichi; Yoh, Kiyotaka

    2014-08-01

    Maintenance therapy is a new treatment strategy for advanced non-small-cell lung cancer(NSCLC), and it consists of switch maintenance and continuation maintenance.Switch maintenance is the introduction of a different drug, not included as part of the induction therapy, immediately after completion of 4 cycles of first-line platinum-based chemotherapy.Continuation maintenance is a continuation of at least one of the drugs used in the induction therapy in the absence of disease progression.Several phase III trials have reported survival benefits with continuation maintenance of pemetrexed and switch maintenance of pemetrexed or erlotinib.Therefore, maintenance therapy has become a part of the standard first-line treatment for advanced NSCLC.However, further research is needed to elucidate the selection criteria of patients who may benefit the most from maintenance therapy. PMID:25132023

  2. Maintenance treatment with chemotherapy and immunotherapy in non-small cell lung cancer: a case report

    PubMed Central

    Llanos, Anabella; Savignano, Mariana; Cinat, Gabriela

    2012-01-01

    A 53-years-old woman was diagnosed with lung adenocarcinoma state IV (synchronous pleural involvement) in April 2009. First-line systemic treatment included six cycles of Carboplatin, Paclitaxel, and Bevacizumab. Partial response was achieved. Maintenance therapy with Bevacizumab and Pemetrexed was given from September 2009 to February 2010. No response changes were observed. Immunotherapy was initiated, and then Pemetrexed was given with the same disease status. Both treatments were well tolerated. Immunotherapy toxicity included reaction at the site of injection grade 2. At present, the patient is still on this treatment. Given the poor prognosis of patients with advanced lung cancer, the combination of both treatments during the stable phase of the disease may improve progression-free survival. PMID:23112957

  3. Hygroscopic behavior of atmospherically relevant water-soluble carboxylic salts and their influence on the water uptake of ammonium sulfate

    NASA Astrophysics Data System (ADS)

    Wu, Z. J.; Nowak, A.; Poulain, L.; Herrmann, H.; Wiedensohler, A.

    2011-12-01

    The hygroscopic behavior of atmospherically relevant water-soluble carboxylic salts and their effects on ammonium sulfate were investigated using a hygroscopicity tandem differential mobility analyzer (H-TDMA). No hygroscopic growth is observed for disodium oxalate, while ammonium oxalate shows slight growth (growth factor = 1.05 at 90%). The growth factors at 90% RH for sodium acetate, disodium malonate, disodium succinate, disodium tartrate, diammonium tartrate, sodium pyruvate, disodium maleate, and humic acid sodium salt are 1.79, 1.78, 1.69, 1.54, 1.29, 1.70, 1.78, and 1.19, respectively. The hygroscopic growth of mixtures of organic salts with ammonium sulfate, which are prepared as surrogates of atmospheric aerosols, was determined. A clear shift in deliquescence relative humidity to lower RH with increasing organic mass fraction was observed for these mixtures. Above 80% RH, the contribution to water uptake by the organic salts was close to that of ammonium sulfate for the majority of investigated compounds. The observed hygroscopic growth of the mixed particles at RH above the deliquescence relative humidity of ammonium sulfate agreed well with that predicted using the Zdanovskii-Stokes-Robinson (ZSR) mixing rule. Mixtures of ammonium sulfate with organic salts are more hygroscopic than mixtures with organic acids, indicating that neutralization by gas-phase ammonia and/or association with cations of dicarbonxylic acids may enhance the hygroscopicity of the atmospheric particles.

  4. Orotate phosphoribosyltransferase is overexpressed in malignant pleural mesothelioma: Dramatically responds one case in high OPRT expression

    PubMed Central

    Hamamoto, Yoichiro; Takeoka, Shinjiro; Mouri, Atsuto; Fukusumi, Munehisa; Wakuda, Kazushige; Ibe, Tatsuya; Honma, Chie; Arimoto, Yoshihito; Yamada, Kazuaki; Wagatsuma, Miyuki; Tashiro, Akito; Kamoshida, Shingo; Kamimura, Mitsuhiro

    2016-01-01

    ABSTRACT Objective: Malignant pleural mesothelioma (MPM) is a rare and aggressive, treatment-resistant cancer. Pemetrexed, an inhibitor of thymidylate synthase (TS), is used worldwide for MPM as a first-line chemotherapy regimen. However, there is little consensus for a second-line chemotherapy. S-1, a highly effective dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidine, mainly acts via a TS inhibitory mechanism similar to pemetrexed. Orotate phosphoribosyltransferase (OPRT) is a key enzyme related to the first step activation of 5-fluorouracil (5-FU) for inhibiting RNA synthesis. We investigated 5-FU related-metabolism proteins, especially focusing on OPRT expression, in MPM Methods and Patients: Fifteen MPM patients who were diagnosed between July 2004 and December 2013 were enrolled. We examined the protein levels of 5-FU metabolism-related enzymes (TS, DPD, OPRT, and thymidine phosphorylase [TP]) in 14 cases Results: High TS, DPD, OPRT, and TP expressions were seen in 28.6%, 71.4%, 85.7%, and 35.7% of patients, respectively. We found that OPRT expression was extremely high in MPM tissue. We experienced one remarkable case of highly effective S-1 combined therapy for pemetrexed refractory MPM. This case also showed high OPRT protein expression Conclusion: The present study suggests that OPRT expression is high in MPM tumors. Although pemetrexed is mainly used for MPM chemotherapy as a TS inhibitor, S-1 has potential as an anticancer drug not only as a TS inhibitor but also inhibiting RNA synthesis through the OPRT pathway. This is the first report investigating OPRT protein expressions in MPM. PMID:27274438

  5. Second-line treatment in advanced non-small-cell lung cancer in the epidermal growth factor receptor wild-type population: review of patient profile.

    PubMed

    Vázquez, Sergio; Lázaro, Martín; Fírvida, José Luis; Santomé, Lucía; Afonso, Javier; Amenedo, Margarita; Casal, Joaquín

    2014-04-01

    After progression during first-line treatment in advanced non-small-cell lung cancer (NSCLC), a large percentage of patients are candidates for second-line treatment. The majority do not have epidermal growth factor receptor-activating mutations (EGFRwt). This article reviews the treatment options available for this subpopulation of patients, which includes essentially docetaxel, pemetrexed and erlotinib. These drugs all have similar efficacy, both in terms of objective response rates and overall survival, although with different toxicity profiles. In view of the similar efficacy of the three agents (docetaxel, pemetrexed and erlotinib) in the second-line treatment of NSCLC in the EGFRwt population, and although there are no prospective studies on predictive variables or new molecular markers available, selection of the treatment will depend on the histological type (pemetrexed); patient preference (oral as opposed to intravenous formulation); the presence of comorbid conditions; quality of life; previous or residual toxicities; the risk of neutropenia; response to and the duration of the first-line chemotherapy; and history of smoking. PMID:24384805

  6. [PARAMOUNT trial: clinical meaning of continuous maintenance therapy in lung cancer].

    PubMed

    Gridelli, Cesare

    2015-05-01

    Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer related deaths worldwide across both sex. Patients with Advanced -NSCLC (A-NSCLC) do not have curative treatment options, so the primary endpoint of every therapeutic decision aims to prolong survival, improving or maintain a good Quality of Life (QoL). Histology could represent a positive predictive factor for patients with Non squamous NSCLC (Nsq-NSCLC) respect to pemetrexed treatment. Pemetrexed is an antifolate that inhibits primarily thymidylate synthase (TS), together with dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. Pemetrexed in combination with cisplatin is approved in the first line setting and as monotherapy in the switch or continuous maintenance of Non Squamous A-NSCLC. Maintenance therapy is a widely used therapeutic option in other solid and hematologic malignancies, but in the A-NSCLC represent an innovative approach. The rationale in this new setting of patients is based on the evidence that patients who benefit from an initial induction therapy platinum based may benefit from maintenance therapy with the third generation agent dropping the platinum drug after four to six cycles. We can define two types of maintenance therapy: continuation maintenance and switch maintenance. Major results in prolonging Overall Survival (OS) was reported with the continuation maintenance strategy as in the PARAMOUNT trial. PMID:25994539

  7. The evolution of cancer research and drug discovery at Lilly Research Laboratories.

    PubMed

    Pearce, Homer L; Alice Miller, Mary

    2005-01-01

    This review highlights the discovery and development of chemotherapy at Eli Lilly & Company over the past 30 years from the Vinca alkaloids-vincristine, vinblastine, and vindesine-to targeted therapy. During the late 1970s, Lilly began an exploration of new synthetic compounds based on solid tumor screening models. Several novel antimetabolites with the potential to treat solid tumors were identified. Two such agents, gemcitabine and pemetrexed, underwent clinical development and are now among Lilly's portfolio of approved anticancer drugs. Gemcitabine, a pyrimidine nucleoside that has a profound effect on DNA synthesis, has been approved for the treatment of pancreatic, non-small cell lung, bladder, and most recently, breast, and ovarian cancer. Pemetrexed, a novel antifolate with potent cytotoxic effects, is distinguished from other antifolates by virtue of its ability to inhibit multiple folate-dependent enzymes. Pemetrexed, given in combination with cisplatin, has been recently approved for the treatment of malignant pleural mesothelioma and as second-line treatment for non-small cell lung cancer. Spurred by advances in the understanding of cancer as a disease process, Lilly's anticancer drug program began to transition to a more "targeted" approach during the 1990s. These efforts have recently culminated in the identification and development of enzastaurin, a PKCbeta inhibitor with potent anti-angiogenic properties. Enzastaurin has shown promising single-agent activity in patients with relapsed diffuse large B-cell lymphoma and recurrent glioblastoma multiforme, and is an excellent candidate for combination with cytotoxic agents. PMID:16143373

  8. An Autopsy Case of Rapidly Progressing Spindle Cell Carcinoma of the Lung Accompanied with Intratumor Hemorrhage

    PubMed Central

    Kida, Jun-ichiro; Kanaji, Nobuhiro; Kishi, Sosuke; Imaida, Katsumi; Bandoh, Shuji

    2015-01-01

    Patient: Male, 74 Final Diagnosis: Spindle cell carcinoma of the lung Symptoms: — Medication: Pemetrexed • carboplatin Clinical Procedure: Biopsy and autopsy Specialty: Oncology Objective: Rare disease Background: Spindle cell carcinoma (SPCC) of the lung is a subset of sarcomatoid carcinoma. Its clinical features are unclear because of its rarity. Here, we report an autopsy case of SPCC and review CT findings and chemotherapeutic regimens based on previous reports of this disease. To our knowledge, this is the first reported case of pemetrexed used to treat SPCC. Case Report: A 74-year-old Japanese male presented with dyspnea and contrast-enhanced computed tomography (CT) showed abundant left pleural effusion and a mass in lower lobe of the left lung. By the tumor biopsy, he was diagnosed for SPCC of the lung, cT3N0M1a, stage IV. The tumor was resistant to chemotherapy with carboplatin and pemetrexed, and rapidly progressed. Autopsy revealed abundant hemorrhage within the tumor, which apparently reflects a low-density area in CT. Conclusions: Present case and the accumulation of cases indicate that low-density areas in CT and rapid tumor progression may be common SPCC findings. PMID:26558362

  9. Racial differences in responses to therapy with interferon in chronic hepatitis C. Consensus Interferon Study Group.

    PubMed

    Reddy, K R; Hoofnagle, J H; Tong, M J; Lee, W M; Pockros, P; Heathcote, E J; Albert, D; Joh, T

    1999-09-01

    The likelihood of a sustained response to a course of interferon in patients with chronic hepatitis C correlates with several clinical and viral factors, including age, viral genotype and initial levels of hepatitis C virus (HCV) RNA in serum. The role of race and ethnicity has not been assessed. We evaluated the association of race with response to interferon in a large randomized, controlled trial using either consensus interferon (9 microg) or interferon alfa-2b (3 million units) given three times weekly for 24 weeks. African-American patients participating in the study were similar to white patients in mean age (43 vs. 42 years) and baseline levels of HCV RNA (3.6 vs. 3.0 million copies/mL) but had lower rates of cirrhosis (5% vs. 12%) and more frequently had viral genotype 1 (88% vs. 66%: P =.004). Most strikingly, the rates of end-of-treatment and sustained virological responses were lower among the 40 African-American patients (5% and 2%) than among the 380 white patients (33% and 12%) (P =.04 and.07). Rates of response among Hispanic and Asian-American patients were not statistically different than non-Hispanic white patients. Median viral levels decreased by week 24 of therapy by 2.5 logs in white patients (from 3.0 to 0.012 million copies/mL) but by only 0.5 logs among African- American patients (from 3.6 to 1.8 million copies/mL). Thus, there are marked racial differences in virological responses to interferon in hepatitis C that must be considered in assessing trials of interferon therapy and in counseling patients regarding treatment. The differences in response rates are as yet unexplained. PMID:10462387

  10. Gateways to Clinical Trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-04-01

    , nevirapine, nifedipine, NSC-683864; Oral heparin; Paclitaxel, peginterferon alfa-2b, phenytoin, pimecrolimus, piperacillin, pleconaril, pramipexole hydrochloride, prednisone, pregabalin, progesterone; Rasburicase, ravuconazole, reteplase, ribavirin, rituximab, rizatriptan, rosiglitazone maleate, rotigotine; Semaxanib, sildenafil citrate, simvastatin, stavudine, sumatriptan; Tacrolimus, tamoxifen citrate, tanomastat, tazobactam, telithromycin, tenecteplase, tolafentrine, tolterodine tartrate, triamcinolone acetonide, trimetazidine, troxacitabine; Valproic acid, vancomycin hydrochloride, vincristine, voriconazole, Warfarin sodium; Ximelagatran, Zidovudine, zolmitriptan. PMID:12087878

  11. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:(R)-Flurbiprofen, 90Yttrium-DOTA-huJ591; ABT-510, ACP-103, Ad5-FGF4, adalimumab, ademetionine, AG-7352, alemtuzumab, Amb a 1 ISS-DNA, anakinra, apaziquone, aprepitant, aripiprazole, atazanavir sulfate; BAL-8557, bevacizumab, BMS-188797, bortezomib, bosentan, brivudine; Calcipotriol/betamethasone dipropionate, cannabidiol, caspofungin acetate, catumaxomab, CERE-120, cetuximab, ciclesonide, cilomilast, cizolirtine citrate, Cypher, cystemustine; Dalbavancin, darifenacin hydrobromide, dasatinib, deferasirox, denosumab, desmoteplase, dihydrexidine, dimethyl fumarate, dutasteride, DW-166HC; Eculizumab, enfuvirtide, entecavir, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, eszopiclone, etoricoxib, everolimus; Fallypride, febuxostat, fenretinide, fesoterodine, fingolimod hydrochloride; Gabapentin enacarbil, gefitinib; hMaxi-K, human papillomavirus vaccine, HYAL-CT1101; Imatinib mesylate, indiplon, inolimomab, ISAtx-247; J591; Lacosamide, landiolol, lasofoxifene tartrate, lestaurtinib, lidocaine/prilocaine, linezolid, lixivaptan, lonafarnib, lopinavir, lopinavir/ritonavir, lumiracoxib; Natalizumab, nesiritide; OC-108, omalizumab, onercept, OSC; Palifermin, palonosetron hydrochloride, parathyroid hormone (human recombinant), parecoxib sodium, PD-MAGE-3 vaccine, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pelitinib, pitavastatin calcium, plerixafor hydrochloride, posaconazole, prasterone sulfate, pregabalin; Ramelteon, ranelic acid distrontium salt, rasburicase, rosuvastatin calcium, rotigotine, RSD-1235, rufinamide, rupatadine fumarate; Sarizotan hydrochloride, SHL-749

  12. Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections.

    PubMed

    Dobbs, Kerry; Domínguez Conde, Cecilia; Zhang, Shen-Ying; Parolini, Silvia; Audry, Magali; Chou, Janet; Haapaniemi, Emma; Keles, Sevgi; Bilic, Ivan; Okada, Satoshi; Massaad, Michel J; Rounioja, Samuli; Alwahadneh, Adel M; Serwas, Nina K; Capuder, Kelly; Çiftçi, Ergin; Felgentreff, Kerstin; Ohsumi, Toshiro K; Pedergnana, Vincent; Boisson, Bertrand; Haskoloğlu, Şule; Ensari, Arzu; Schuster, Michael; Moretta, Alessandro; Itan, Yuval; Patrizi, Ornella; Rozenberg, Flore; Lebon, Pierre; Saarela, Janna; Knip, Mikael; Petrovski, Slavé; Goldstein, David B; Parrott, Roberta E; Savas, Berna; Schambach, Axel; Tabellini, Giovanna; Bock, Christoph; Chatila, Talal A; Comeau, Anne Marie; Geha, Raif S; Abel, Laurent; Buckley, Rebecca H; İkincioğulları, Aydan; Al-Herz, Waleed; Helminen, Merja; Doğu, Figen; Casanova, Jean-Laurent; Boztuğ, Kaan; Notarangelo, Luigi D

    2015-06-18

    Background Combined immunodeficiencies are marked by inborn errors of T-cell immunity in which the T cells that are present are quantitatively or functionally deficient. Impaired humoral immunity is also common. Patients have severe infections, autoimmunity, or both. The specific molecular, cellular, and clinical features of many types of combined immunodeficiencies remain unknown. Methods We performed genetic and cellular immunologic studies involving five unrelated children with early-onset invasive bacterial and viral infections, lymphopenia, and defective T-cell, B-cell, and natural killer (NK)-cell responses. Two patients died early in childhood; after allogeneic hematopoietic stem-cell transplantation, the other three had normalization of T-cell function and clinical improvement. Results We identified biallelic mutations in the dedicator of cytokinesis 2 gene (DOCK2) in these five patients. RAC1 activation was impaired in the T cells. Chemokine-induced migration and actin polymerization were defective in the T cells, B cells, and NK cells. NK-cell degranulation was also affected. Interferon-α and interferon-λ production by peripheral-blood mononuclear cells was diminished after viral infection. Moreover, in DOCK2-deficient fibroblasts, viral replication was increased and virus-induced cell death was enhanced; these conditions were normalized by treatment with interferon alfa-2b or after expression of wild-type DOCK2. Conclusions Autosomal recessive DOCK2 deficiency is a new mendelian disorder with pleiotropic defects of hematopoietic and nonhematopoietic immunity. Children with clinical features of combined immunodeficiencies, especially with early-onset, invasive infections, may have this condition. (Supported by the National Institutes of Health and others.). PMID:26083206

  13. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a, Abacavir sulfate/lamivudine, Adalimumab, Aliskiren fumarate, Ambrisentan, Aripiprazole, AT-7519, Atazanavir sulfate, Atomoxetine hydrochloride, Azacitidine, Azelnidipine; Besifloxacin hydrochloride, Bevacizumab, Bioabsorbable everolimus-eluting coronary stent, Bortezomib, Bosentan, Budesonide/formoterol fumarate; CAIV-T, Carisbamate, Casopitant mesylate, Certolizumab pegol, Cetuximab, Ciclesonide, Ciprofloxacin/dexamethasone, CTCE-9908; Dalcetrapib, Darunavir, Deferasirox, Desloratadine, Disitertide, Drotrecogin alfa (activated), DTA-H19, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Efalizumab, Emtricitabine, Eribulin mesilate, Escitalopram oxalate, Eszopiclone, EUR-1008, Everolimus-eluting coronary stent, Exenatide; Fampridine, Fluticasone furoate, Formoterol fumarate/fluticasone propionate, Fosamprenavir calcium, Fulvestrant; Gabapentin enacarbil, GS-7904L; HPV-6/11/16/18, Human Secretin, Hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, Imexon, Inalimarev/Falimarev, Indacaterol, Indacaterol maleate, Inhalable human insulin, Insulin detemir, Insulin glargine, Ixabepilone; L-Alanosine, Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Loratadine/montelukast sodium, Lutropin alfa; MeNZB, Mepolizumab, Micafungin sodium, Morphine hydrochloride; Nabiximols, Nikkomycin Z; Olmesartan medoxomil, Omalizumab; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Perifosine, PF-489791, Plitidepsin, Posaconazole, Pregabalin; QAX-576; Raltegravir potassium, Ramelteon, Rasagiline

  14. Quality-of-life evaluation in an interferon therapy after radical surgery in cutaneous melanoma patients.

    PubMed

    Rataj, Dorota; Jankowiak, Barbara; Krajewska-Kułak, Elzbieta; Van Damme-Ostapowicz, Katarzyna; Nowecki, Zbigniew I; Rutkowski, Piotr; Niczyporuk, Wiaczesław

    2005-01-01

    Melanoma is the fastest growing solid tumor in men and women, and despite accounting for only 4% of skin cancer cases, it accounts for more than 79% of skin cancer-related deaths. The present study was designed to evaluate the impact of interferon (IFN) treatment on patients' quality of life (QOL) after radical surgery of cutaneous melanoma. The tests were carried out in a group of patients treated in the Department of Soft Tissue and Bone Cancer, Institute of Oncology, in Warsaw. The present study included 2 groups of the patients, 110 persons each. One group consisted of patients who had been subjected to radical surgery of cutaneous melanoma, and the other one consisted of 110 patients treated with a supplementary interferon alfa-2b (IFN-alpha-2b) therapy. Data were collected by means of an anonymous QLQ-C30 (version 2.0.) questionnaire elaborated and provided by the European Organisation for Research and Treatment of Cancer. The QLQ-C30 questionnaire consisted of 43 questions. The IFN-alpha-2b treatment significantly affected patients' physical condition, mental health, and social life. The emotional state of the patients was more affected during IFN-alpha-2b treatment. Somatic symptoms were also increased in those patients. The IFN-alpha-2b therapy also significantly affected family and social life. In spite of several adverse effects, the patients assessed their QOL as good. The IFN-alpha-2b treatment is troublesome for the melanoma patients. It is important that the treating physician and nurse should be aware of the 4 major categories of IFN-alpha-2b toxicity: constitutional, neuropsychiatric, hepatic, and hematologic. A number of steps can be taken to minimize the morbidity associated with IFN-alpha-2b therapy, resulting in an improvement in both QOL and patient compliance. PMID:15915059

  15. ASSESSMENT OF BORIC ACID AND BORAX USING THE IEHR EVALUATIVE PROCESS FOR ASSESSING HUMAN DEVELOPMENT AND REPRODUCTIVE TOXICITY OF AGENTS

    EPA Science Inventory

    This document presents an evaluation of the reproductive and developmental effects of boric acid, H3803 (CAS Registry No. 10043-35-3) and disodium tetraborate decehydrate or borax, Na2B4O2O(CAS Registry No. 1303-96-4). he element, boron, does not exist naturally. oron always exis...

  16. Effects of dietary supplementation of a purified nucleotide mixture on growth, immune function, and disease and stress resistance in channel catfish, Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Juvenile channel catfish (14.4 g average initial weight) were fed diets supplemented with a purified nucleotide mixture for 8 weeks. The mixture consisted of five nucleotides supplied on an equal basis as disodium salts at combined concentrations of 0 (control), 0.1, 0.3, 0.9, or 2.7% of diet. At th...

  17. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... compound is coupled with 6-hydroxy-2-naphthalene-sulfonic acid. The dye is isolated as the sodium salt and...&C Yellow No. 6 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid (CAS Reg. No. 2783-94-0). The trisodium salt of 3-hydroxy-4- -2,7-naphthalenedisulfonic acid (CAS Reg....

  18. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... compound is coupled with 6-hydroxy-2-naphthalene-sulfonic acid. The dye is isolated as the sodium salt and...&C Yellow No. 6 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid (CAS Reg. No. 2783-94-0). The trisodium salt of 3-hydroxy-4- -2,7-naphthalenedisulfonic acid (CAS Reg....

  19. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... compound is coupled with 6-hydroxy-2-naphthalene-sulfonic acid. The dye is isolated as the sodium salt and...&C Yellow No. 6 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid (CAS Reg. No. 2783-94-0). The trisodium salt of 3-hydroxy-4- -2,7-naphthalenedisulfonic acid (CAS Reg....

  20. 21 CFR 74.1708 - D&C Yellow No. 8.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1708 D&C Yellow No. 8. (a) Identity. (1) The color additive D&C Yellow No. 8 is principally the disodium salt of fluorescein. (2) Color additive mixtures for use... suitable and that are listed in part 73 of this chapter for use in color additive mixtures for...

  1. 21 CFR 74.1707a - Ext. D&C Yellow No. 7.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... color additive Ext. D&C Yellow No. 7 is principally the disodium salt of 8-hydroxy-5,7-di-nitro-2-naphthalenesulfonic acid. (2) Color additive mixtures for drug use made with Ext. D&C Yellow No. 7 may contain only... additive mixtures for coloring externally applied drugs. (b) Specifications. Ext. D&C Yellow No. 7...

  2. 21 CFR 74.1708 - D&C Yellow No. 8.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1708 D&C Yellow No. 8. (a) Identity. (1) The color additive D&C Yellow No. 8 is principally the disodium salt of fluorescein. (2) Color additive mixtures for use... suitable and that are listed in part 73 of this chapter for use in color additive mixtures for...

  3. 21 CFR 74.1708 - D&C Yellow No. 8.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1708 D&C Yellow No. 8. (a) Identity. (1) The color additive D&C Yellow No. 8 is principally the disodium salt of fluorescein. (2) Color additive mixtures for use... suitable and that are listed in part 73 of this chapter for use in color additive mixtures for...

  4. 21 CFR 74.1707a - Ext. D&C Yellow No. 7.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... color additive Ext. D&C Yellow No. 7 is principally the disodium salt of 8-hydroxy-5,7-di-nitro-2-naphthalenesulfonic acid. (2) Color additive mixtures for drug use made with Ext. D&C Yellow No. 7 may contain only... additive mixtures for coloring externally applied drugs. (b) Specifications. Ext. D&C Yellow No. 7...

  5. 21 CFR 74.1707a - Ext. D&C Yellow No. 7.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... color additive Ext. D&C Yellow No. 7 is principally the disodium salt of 8-hydroxy-5,7-di-nitro-2-naphthalenesulfonic acid. (2) Color additive mixtures for drug use made with Ext. D&C Yellow No. 7 may contain only... additive mixtures for coloring externally applied drugs. (b) Specifications. Ext. D&C Yellow No. 7...

  6. Dynamic NMR of Intramolecular Exchange Processes in EDTA Complexes of Sc[superscript 3+], Y[superscript 3+], and La[superscript 3+

    ERIC Educational Resources Information Center

    Ba, Yong; Han, Steven; Ni, Lily; Su, Tony; Garcia, Andres

    2006-01-01

    Dynamic NMR makes use of the effect of chemical exchanges on NMR spectra to study kinetics and thermodynamics. An advanced physical chemistry lab experiment was developed to study the intramolecular exchange processes of EDTA (the disodium salt of ethylenediaminetetraacetic acid) metal complexes. EDTA is an important chelating agent, used in…

  7. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-aminobenzenesulfonic acid using hydrochloric acid and sodium nitrite or sulfuric acid and sodium nitrite. The diazo...&C Yellow No. 6 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid (CAS Reg. No. 2783-94-0). The trisodium salt of 3-hydroxy-4- -2,7-naphthalenedisulfonic acid (CAS Reg....

  8. 21 CFR 74.1306 - D&C Red No. 6.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Red No. 6 is principally the disodium salt of 3-hydroxy-4- -2-naphthalenecarboxylic acid (CAS Reg. No. 5858-81-1). To manufacture the additive, 2-amino-5-methylbenzenesulfonic acid is diazotized with hydrochloric acid and sodium nitrite. The diazo compound is coupled in alkaline medium with...

  9. 21 CFR 74.1306 - D&C Red No. 6.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Red No. 6 is principally the disodium salt of 3-hydroxy-4- -2-naphthalenecarboxylic acid (CAS Reg. No. 5858-81-1). To manufacture the additive, 2-amino-5-methylbenzenesulfonic acid is diazotized with hydrochloric acid and sodium nitrite. The diazo compound is coupled in alkaline medium with...

  10. 21 CFR 74.1306 - D&C Red No. 6.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Red No. 6 is principally the disodium salt of 3-hydroxy-4- -2-naphthalenecarboxylic acid (CAS Reg. No. 5858-81-1). To manufacture the additive, 2-amino-5-methylbenzenesulfonic acid is diazotized with hydrochloric acid and sodium nitrite. The diazo compound is coupled in alkaline medium with...

  11. 21 CFR 74.1306 - D&C Red No. 6.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Red No. 6 is principally the disodium salt of 3-hydroxy-4- -2-naphthalenecarboxylic acid (CAS Reg. No. 5858-81-1). To manufacture the additive, 2-amino-5-methylbenzenesulfonic acid is diazotized with hydrochloric acid and sodium nitrite. The diazo compound is coupled in alkaline medium with...

  12. 76 FR 25334 - Notice of Receipt of Requests To Voluntarily Cancel Certain Pesticide Registrations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-04

    .... 047371-00150 TB-910 Disinfectant Hydrochloric acid. Bowl Cleaner & 1-Decanaminium, N- Deodorant. decyl-N...%C16). 047371-00172 TB-A165 Hydrochloric acid. Disinfectant Bowl Cleaner. 1-Decanaminium, N- decyl-N,N... acid, methyl- monopotassium salt. Carbamodithioic acid, cyano- disodium salt. 005481-00551 Ambush...

  13. 21 CFR 74.1306 - D&C Red No. 6.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Red No. 6 is principally the disodium salt of 3-hydroxy-4- -2-naphthalenecarboxylic acid (CAS Reg. No. 5858-81-1). To manufacture the additive, 2-amino-5-methylbenzenesulfonic acid is diazotized with hydrochloric acid and sodium nitrite. The diazo compound is coupled in alkaline medium with...

  14. 21 CFR 74.1304 - FD&C Red No. 4.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... than 0.2 percent. 5-Amino-2,4-dimethyl-1-benzenesulfonic acid, sodium salt, not more than 0.2 percent. 4-Hydroxy-1-naphthalenesulfonic acid, sodium salt, not more than 0.2 percent. Subsidiary colors, not... Red No. 4 is principally the disodium salt of 3- -4-hydroxy-1-naphthalenesulfonic acid. (2)...

  15. 21 CFR 74.1333 - D&C Red No. 33.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Red No. 33 is principally the disodium salt of 5-amino-4-hydroxy-3-(phenylazo)-2,7-naphthalenedisulfonic acid (CAS Reg. No. 3567-66-6). To manufacture the additive, the product obtained from the nitrous acid diazotization of aniline is coupled with 4-hydroxy-5-amino-2,7-naphthalenedisulfonic acid in...

  16. 21 CFR 74.340 - FD&C Red No. 40.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-naphthalenesulfonic acid, not more than 1.0 percent. Sodium salt of 6-hydroxy-2-naphthalenesulfonic acid (Schaeffer's salt), not more than 0.3 percent. 4-Amino-5-methoxy-o- toluenesulfonic acid, not more than 0.2 percent... Red No. 40 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid. (2)...

  17. 21 CFR 74.340 - FD&C Red No. 40.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-naphthalenesulfonic acid, not more than 1.0 percent. Sodium salt of 6-hydroxy-2-naphthalenesulfonic acid (Schaeffer's salt), not more than 0.3 percent. 4-Amino-5-methoxy-o- toluenesulfonic acid, not more than 0.2 percent... Red No. 40 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid. (2)...

  18. 21 CFR 74.1333 - D&C Red No. 33.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Red No. 33 is principally the disodium salt of 5-amino-4-hydroxy-3-(phenylazo)-2,7-naphthalenedisulfonic acid (CAS Reg. No. 3567-66-6). To manufacture the additive, the product obtained from the nitrous acid diazotization of aniline is coupled with 4-hydroxy-5-amino-2,7-naphthalenedisulfonic acid in...

  19. 21 CFR 74.1304 - FD&C Red No. 4.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... than 0.2 percent. 5-Amino-2,4-dimethyl-1-benzenesulfonic acid, sodium salt, not more than 0.2 percent. 4-Hydroxy-1-naphthalenesulfonic acid, sodium salt, not more than 0.2 percent. Subsidiary colors, not... Red No. 4 is principally the disodium salt of 3- -4-hydroxy-1-naphthalenesulfonic acid. (2)...

  20. 21 CFR 74.1304 - FD&C Red No. 4.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... than 0.2 percent. 5-Amino-2,4-dimethyl-1-benzenesulfonic acid, sodium salt, not more than 0.2 percent. 4-Hydroxy-1-naphthalenesulfonic acid, sodium salt, not more than 0.2 percent. Subsidiary colors, not... Red No. 4 is principally the disodium salt of 3- -4-hydroxy-1-naphthalenesulfonic acid. (2)...

  1. 21 CFR 74.340 - FD&C Red No. 40.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-naphthalenesulfonic acid, not more than 1.0 percent. Sodium salt of 6-hydroxy-2-naphthalenesulfonic acid (Schaeffer's salt), not more than 0.3 percent. 4-Amino-5-methoxy-o- toluenesulfonic acid, not more than 0.2 percent... Red No. 40 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid. (2)...

  2. Estimation of free acid content in lanthanide salt solutions used for potentiometric determination of stability constant of lanthanide complexes with organic ligands

    SciTech Connect

    Zheltvai, T.I.; Tishchenko, M.A.

    1985-08-20

    This paper studies the possibility of alkalimetric titration of free acid after binding the metal ions by the disodium salt of ethylenediaminetetraacetic (complexone III). The proposed method of free acid determination in lanthanide salt solutions is very simple and helps to avoid gross methodical errors in works involving determination of stability constants of lanthanide complexes.

  3. Effect of short-term feeding duration of diets containing commercial whole-cell yeast or yeast subcomponents on immune function and disease resistance in channel catfish, Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Juvenile channel catfish (14.4 g average initial weight) were fed diets supplemented with a purified nucleotide mixture for 8 weeks. The mixture consisted of five nucleotides supplied on an equal basis as disodium salts at combined concentrations of 0 (control), 0.1, 0.3, 0.9, or 2.7% of diet. At th...

  4. 40 CFR 721.9795 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[(4,6-dichloro-1,3,5-triazin-2-yl) amino...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Benzenesulfonic acid, 2,2â²-(1,2... Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with dialkyl amines (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance...

  5. 21 CFR 74.2101 - FD&C Blue No. 1.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FD&C Blue No. 1. 74.2101 Section 74.2101 Food and... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2101 FD&C Blue No. 1. (a) Identity. The color additive FD&C Blue No. 1 is principally the disodium salt of ethyl...

  6. 21 CFR 74.2101 - FD&C Blue No. 1.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FD&C Blue No. 1. 74.2101 Section 74.2101 Food and... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2101 FD&C Blue No. 1. (a) Identity. The color additive FD&C Blue No. 1 is principally the disodium salt of ethyl...

  7. 21 CFR 74.2101 - FD&C Blue No. 1.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FD&C Blue No. 1. 74.2101 Section 74.2101 Food and... ADDITIVES SUBJECT TO CERTIFICATION Cosmetics § 74.2101 FD&C Blue No. 1. (a) Identity. The color additive FD&C Blue No. 1 is principally the disodium salt of ethyl...

  8. 21 CFR 155.170 - Canned peas.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN.... (iv) Disodium guanylate. (v) Hydrolyzed vegetable protein. (vi) Autolyzed yeast extract. (vii) One or... vegetable or animal fats or oils in a quantity not less than 2.4 percent by weight of the finished...

  9. 21 CFR 155.170 - Canned peas.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN.... (iv) Disodium guanylate. (v) Hydrolyzed vegetable protein. (vi) Autolyzed yeast extract. (vii) One or... vegetable or animal fats or oils in a quantity not less than 2.4 percent by weight of the finished...

  10. 21 CFR 155.170 - Canned peas.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN.... (iv) Disodium guanylate. (v) Hydrolyzed vegetable protein. (vi) Autolyzed yeast extract. (vii) One or... vegetable or animal fats or oils in a quantity not less than 2.4 percent by weight of the finished...

  11. 21 CFR 155.170 - Canned peas.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN.... (iv) Disodium guanylate. (v) Hydrolyzed vegetable protein. (vi) Autolyzed yeast extract. (vii) One or... vegetable or animal fats or oils in a quantity not less than 2.4 percent by weight of the finished...

  12. 21 CFR 155.170 - Canned peas.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN.... (iv) Disodium guanylate. (v) Hydrolyzed vegetable protein. (vi) Autolyzed yeast extract. (vii) One or... vegetable or animal fats or oils in a quantity not less than 2.4 percent by weight of the finished...

  13. 77 FR 50661 - Notice of Filing of Several Pesticide Petitions Filed for Residues of Pesticide Chemicals in or...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-22

    ...-I CHEMICAL U.S.A., INC., c/o Landis International, Inc., P.O. Box 5126, Valdosta, GA 31603-5126... chemical name of FD&C Red No. 40 is 2-naphthalenesulfonic acid, 6- hydroxy-5- -, disodium salt (CAS No... related reaction products, herein referred to as methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate,...

  14. DOES IRON OR HEME CONTROL RAT HEPATIC DELTA-AMINOLEVULINIC ACID SYNTHETASE ACTIVITY

    EPA Science Inventory

    Disodium ethylenediamine tetraacetic acid and/or allylisopropylacetamide administration to rat pups did not evoke a premature induction of hepatic d-aminolevulinic acid synthetase. Administration of iron to adult rats did not alter d-aminolevulinic acid synthetase activity and ha...

  15. 21 CFR 74.303 - FD&C Red No. 3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ADDITIVES SUBJECT TO CERTIFICATION Foods § 74.303 FD&C Red No. 3. (a) Identity. (1) The color additive FD&C...-xanthen-3-one, disodium salt, with smaller amounts of lower imdinated fluoresceins. (2) Color additive... are listed in part 73 of this chapter as safe for use in color additive mixtures for coloring...

  16. 21 CFR 529.2464 - Ticarcillin powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ticarcillin powder. 529.2464 Section 529.2464 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... powder. (a) Specifications. Each vial contains ticarcillin disodium equivalent to 6 grams of...

  17. 21 CFR 529.2464 - Ticarcillin powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ticarcillin powder. 529.2464 Section 529.2464 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... powder. (a) Specifications. Each vial contains ticarcillin disodium equivalent to 6 grams of...

  18. 21 CFR 173.320 - Chemicals for controlling microorganisms in cane-sugar and beet-sugar mills.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... controlling microorganisms in cane-sugar and beet-sugar mills. Agents for controlling microorganisms in cane... used in the control of microorganisms in cane-sugar and/or beet-sugar mills as specified in paragraph...) Combination for cane-sugar mills: Parts per million Disodium cyanodithioimidocarbonate 2.5 Ethylenediamine...

  19. 21 CFR 74.1708 - D&C Yellow No. 8.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1708 D&C Yellow No. 8. (a) Identity. (1) The color additive D&C Yellow No. 8 is principally the disodium salt of fluorescein. (2) Color additive mixtures for use... suitable and that are listed in part 73 of this chapter for use in color additive mixtures for...

  20. 21 CFR 74.1707a - Ext. D&C Yellow No. 7.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... color additive Ext. D&C Yellow No. 7 is principally the disodium salt of 8-hydroxy-5,7-di-nitro-2-naphthalenesulfonic acid. (2) Color additive mixtures for drug use made with Ext. D&C Yellow No. 7 may contain only... additive mixtures for coloring externally applied drugs. (b) Specifications. Ext. D&C Yellow No. 7...

  1. Structures and Absolute Configurations of Sulfate-Conjugated Triterpenoids Including an Antifungal Chemical Defense of the Green Macroalga Tydemania expeditionis

    PubMed Central

    Jiang, Ren-Wang; Lane, Amy L.; Mylacraine, Lauren; Hardcastle, Kenneth I.; Fairchild, Craig R.; Aalbersberg, William; Hay, Mark E.; Kubanek, Julia

    2012-01-01

    Cytotoxicity-guided fractionation of the green macroalga Tydemania expeditionis led to isolation of four sulfate-conjugated triterpenoids including one new lanostane-type triterpenoid disulfate, lanosta-8-en-3,29-diol-23-oxo-3,29-disodium sulfate (1), and three known cycloartane-type triterpenoid disulfates, cycloartan-3,29-diol-23-one 3,29-disodium sulfate (2), cycloart-24-en-3,29-diol-23-one 3,29-disodium sulfate (3), and cycloartan-3,23,29-triol 3,29-disodium sulfate (4). Extensive 1D and 2D NMR analyses in combination with X-ray crystallography established the structure and absolute configuration of 1 and allowed determination of the absolute configurations of 2–4 with a revision of previously assigned configuration at C-5. Each natural product was moderately cytotoxic in tumor cell and invertebrate toxicity assays. Of the natural products, only 4 exhibited significant antifungal activity at whole-tissue natural concentrations against the marine pathogen Lindra thalassiae. Comparison of the biological activities of natural products with their desulfated derivatives indicated that sulfation does not appear to confer cytotoxicity or antifungal activity. PMID:18763828

  2. A field method for the determination of calcium and magnesium in limestone and dolomite

    USGS Publications Warehouse

    Shapiro, Leonard; Brannock, Walter Wallace

    1957-01-01

    The method is an adaptation of a procedure described by Betz and Noll1 in 1950. Calcium and magnesium are determined by visual titration using Versene (disodium ethylenediamine tetraacetate) with Murexide (ammonium purpurate) as the indicator for calcium and Eriochrome Black T as the indicator for magnesium.

  3. Effects of dietary supplementation of a purified nucleotide mixture on immune function and disease and stress resistance in channel catfish, Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Juvenile channel catfish (14.4 g average initial weight) were fed diets supplemented with a purified nucleotide mixture for 8 weeks. The mixture consisted of five nucleotides supplied on an equal basis as disodium salts at combined concentrations of 0 (control), 0.1, 0.3, 0.9, or 2.7% of diet. At th...

  4. Variation in Drug Sensitivity of Malignant Mesothelioma Cell Lines with Substantial Effects of Selenite and Bortezomib, Highlights Need for Individualized Therapy

    PubMed Central

    Szulkin, Adam; Nilsonne, Gustav; Mundt, Filip; Wasik, Agata M.; Souri, Pega; Hjerpe, Anders; Dobra, Katalin

    2013-01-01

    Background Malignant mesothelioma cells have an epithelioid or sarcomatoid morphology, both of which may be present in the same tumor. The sarcomatoid phenotype is associated with worse prognosis and heterogeneity of mesothelioma cells may contribute to therapy resistance, which is often seen in mesothelioma. This study aimed to investigate differences in sensitivity between mesothelioma cell lines to anti-cancer drugs. We studied two novel drugs, selenite and bortezomib and compared their effect to four conventional drugs. We also investigated the immunoreactivity of potential predictive markers for drug sensitivity; Pgp, MRP-1, ERCC1, RRM1, TS, xCT and proteasome 20S subunit. Materials and methods We treated six mesothelioma cell lines with selenite, bortezomib, carboplatin, pemetrexed, doxorubicin or gemcitabine as single agents and in combinations. Viability was measured after 24 and 48 hours. Immunocytochemistry was used to detect predictive markers. Results As a single agent, selenite was effective on four out of six cell lines, and in combination with bortezomib yielded the greatest response in the studied mesothelioma cell lines. Cells with an epithelioid phenotype were generally more sensitive to the different drugs than the sarcomatoid cells. Extensive S-phase arrest was seen in pemetrexed-sensitive cell lines. MRP-1 predicted sensitivity of cell lines to treatment with carboplatin and xCT predicted pemetrexed effect. Conclusions The observed heterogeneity in sensitivity of mesothelioma cell lines with different morphology highlights the need for more individualized therapy, requiring development of methods to predict drug sensitivity of individual tumors. Selenite and bortezomib showed a superior effect compared to conventional drugs, motivating clinical testing of these agents as future treatment regime components for patients with malignant mesothelioma. PMID:23840376

  5. Cost Effectiveness of Personalized Therapy for First-Line Treatment of Stage IV and Recurrent Incurable Adenocarcinoma of the Lung

    PubMed Central

    Handorf, Elizabeth A.; McElligott, Sean; Vachani, Anil; Langer, Corey J.; Bristol Demeter, Mirar; Armstrong, Katrina; Asch, David A.

    2012-01-01

    Purpose: Patients with epidermal growth factor receptor (EGFR) mutation–positive stage IV adenocarcinoma have improved survival with tyrosine kinase inhibitor (TKI) treatments, but the cost effectiveness of personalized first-line therapy using EGFR mutation testing is unknown. Methods: We created a decision analytic model comparing the costs and effects of platinum combination chemotherapy with personalized therapy in which patients with EGFR mutation–positive tumors were treated with erlotinib. We used two testing strategies: testing only those with tissue available and performing a repeat biopsy if tissue was not available versus three nontargeted chemotherapy regimens (ie, carboplatin and paclitaxel; carboplatin and pemetrexed; and carboplatin, pemetrexed, and bevacizumab). Results: Compared with a carboplatin plus paclitaxel regimen, targeted therapy based on testing available tissue yielded an incremental cost-effectiveness ratio (ICER) of $110,644 per quality-adjusted life year (QALY), and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Probabilistic sensitivity analysis revealed substantial uncertainty around these point estimates. With a willingness to pay of $100,000 per QALY, the testing strategy was cost effective 58% of the time, and the rebiopsy strategy was cost effective 54% of the time. Personalized therapy with an EGFR TKI was more favorable when the nontargeted chemotherapy regimen was more expensive. Compared with carboplatin, pemetrexed, and bevacizumab, ICERs were $25,547 per QALY for the testing strategy and $44,036 per QALY for the rebiopsy strategy. Conclusion: Although specific clinical circumstances should guide therapy, our cost-effectiveness analysis supports the strategy of testing for EGFR mutations in patients with stage IV or recurrent adenocarcinoma of the lung, rebiopsying patients if insufficient tissue is available for testing, and treating patients with EGFR mutations with erlotinib as first-line therapy. PMID

  6. Biomarkers that currently affect clinical practice: EGFR, ALK, MET, KRAS

    PubMed Central

    Vincent, M.D.; Kuruvilla, M.S.; Leighl, N.B.; Kamel–Reid, S.

    2012-01-01

    New drugs such as pemetrexed, the epidermal growth factor receptor (egfr) tyrosine kinase inhibitors, and the Alk inhibitor crizotinib have recently enabled progress in the management of advanced non-small-cell lung cancer (nsclc). More drugs, especially Met inhibitors, will follow. However, the benefits of these agents are not uniform across the spectrum of nsclc, and optimizing their utility requires some degree of subgrouping of nsclc by the presence or absence of certain biomarkers. The biomarkers of current or imminent value are EGFR and KRAS mutational status, ALK rearrangements, and MET immunohistochemistry. As a predictor of benefit for anti-egfr monoclonal antibodies, EGFR immunohistochemistry is also of potential interest. Some of the foregoing biomarkers (EGFR, ALK, MET) are direct drivers of the malignant phenotype. As such, they are, quite rationally, the direct targets of inhibitory drugs. However, KRAS, while definitely a driver, has resisted attempts at direct pharmacologic manipulation, and its main value might lie in its role as part of an efficient testing algorithm, because KRAS mutations appear to exclude EGFR and ALK mutations. The indirect value of KRAS in determining sensitivity to other targeted agents or to pemetrexed remains controversial. The other biomarkers (EGFR, ALK, MET) may also have indirect value as predictors of sensitivity to chemotherapy in general, to pemetrexed specifically, and to radiotherapy and molecularly targeted agents. These biomarkers have all enabled the co-development of new drugs with companion diagnostics, and they illustrate the paradigm that will govern progress in oncology in the immediate future. However, in nsclc, the acquisition of sufficient biopsy material remains a stubborn obstacle to the evolution of novel targeted therapies. PMID:22787409

  7. Cynara scolymus affects malignant pleural mesothelioma by promoting apoptosis and restraining invasion

    PubMed Central

    Pulito, Claudio; Mori, Federica; Sacconi, Andrea; Casadei, Luca; Ferraiuolo, Maria; Valerio, Maria Cristina; Santoro, Raffaela; Goeman, Frauke; Maidecchi, Anna; Mattoli, Luisa; Manetti, Cesare; Di Agostino, Silvia; Muti, Paola; Blandino, Giovanni; Strano, Sabrina

    2015-01-01

    Malignant pleural mesothelioma is a poorly treated neoplasia arising from the pleural mesothelial lining. Here we document that the leaf extract of Cynara scolymus exerts broad antitumoral effects both in vitro and in vivo on mesothelioma cell lines. We found that Cynara scolymus treatment affects strongly cell growth, migration and tumor engraftment of mesothelioma cell lines. Strikingly, dietary feeding with Cynara scolymus leaf extract reduces the growth of mesothelioma xenografted tumors similarly to pemetrexed, a commonly employed drug in the treatment of mesothelioma. In aggregate our findings suggest that leaf extract of Cynara scolymus holds therapeutic potential for the treatment of mesothelioma. PMID:26136339

  8. Cynara scolymus affects malignant pleural mesothelioma by promoting apoptosis and restraining invasion.

    PubMed

    Pulito, Claudio; Mori, Federica; Sacconi, Andrea; Casadei, Luca; Ferraiuolo, Maria; Valerio, Maria Cristina; Santoro, Raffaela; Goeman, Frauke; Maidecchi, Anna; Mattoli, Luisa; Manetti, Cesare; Di Agostino, Silvia; Muti, Paola; Blandino, Giovanni; Strano, Sabrina

    2015-07-20

    Malignant pleural mesothelioma is a poorly treated neoplasia arising from the pleural mesothelial lining. Here we document that the leaf extract of Cynara scolymus exerts broad antitumoral effects both in vitro and in vivo on mesothelioma cell lines. We found that Cynara scolymus treatment affects strongly cell growth, migration and tumor engraftment of mesothelioma cell lines. Strikingly, dietary feeding with Cynara scolymus leaf extract reduces the growth of mesothelioma xenografted tumors similarly to pemetrexed, a commonly employed drug in the treatment of mesothelioma. In aggregate our findings suggest that leaf extract of Cynara scolymus holds therapeutic potential for the treatment of mesothelioma. PMID:26136339

  9. The Major Facilitative Folate Transporters Solute Carrier 19A1 and Solute Carrier 46A1: Biology and Role in Antifolate Chemotherapy of Cancer

    PubMed Central

    Wilson, Mike R.; Hou, Zhanjun

    2014-01-01

    This review summarizes the biology of the major facilitative membrane transporters, the reduced folate carrier (RFC) (Solute Carrier 19A1) and the proton-coupled folate transporter (PCFT) (Solute Carrier 46A1). Folates are essential vitamins, and folate deficiency contributes to a variety of health disorders. RFC is ubiquitously expressed and is the major folate transporter in mammalian cells and tissues. PCFT mediates the intestinal absorption of dietary folates and appears to be important for transport of folates into the central nervous system. Clinically relevant antifolates for cancer, such as methotrexate and pralatrexate, are transported by RFC, and loss of RFC transport is an important mechanism of methotrexate resistance in cancer cell lines and in patients. PCFT is expressed in human tumors, and is active at pH conditions associated with the tumor microenvironment. Pemetrexed is an excellent substrate for both RFC and PCFT. Novel tumor-targeted antifolates related to pemetrexed with selective membrane transport by PCFT over RFC are being developed. In recent years, there have been major advances in understanding the structural and functional properties and the regulation of RFC and PCFT. The molecular bases for methotrexate resistance associated with loss of RFC transport and for hereditary folate malabsorption, attributable to mutant PCFT, were determined. Future studies should continue to translate molecular insights from basic studies of RFC and PCFT biology into new therapeutic strategies for cancer and other diseases. PMID:24396145

  10. Vinca alkaloids in the therapeutic management of malignant pleural mesothelioma.

    PubMed

    Ceresoli, Giovanni Luca; Zucali, Paolo Andrea

    2015-12-01

    Therapeutic options for malignant pleural mesothelioma (MPM) are limited. Most patients are treated with chemotherapy during the course of their disease. The combination of pemetrexed with a platinum compound is the standard of care in the first-line setting, while no established treatment exists in the second and beyond-line setting. Vinca alkaloids are chemotherapeutic agents that have demonstrated clinical efficacy both as single agents and in combination in a broad spectrum of cancers, including MPM. Vinorelbine has shown activity in MPM patients as neoadjuvant therapy, first-line treatment, and in the second and third-line setting. Vinflunine is a derivative of vinorelbine that has been studied in MPM as first-line agent. While the role of vinca alkaloids in the first-line treatment of MPM seems marginal, treatment with vinorelbine remains a reasonable option for pemetrexed-pretreated patients in clinical practice, based on an acceptable rate of stable disease, confirmed by several trials. Ongoing studies on predictive biomarkers for vinorelbine will hopefully be able to individualize treatment, increasing response rates and survival outcomes. PMID:26526504

  11. Co-clinical trials demonstrate superiority of crizotinib to chemotherapy in ALK-rearranged non-small cell lung cancer and predict strategies to overcome resistance

    PubMed Central

    Tupper, Tanya; Cheng, Katherine; Wang, Yuchuan; Tan, Xiaohong; Altabef, Abigail; Woo, Sue-Ann; Chen, Liang; Reibel, Jacob B.; Janne, Pasi A.; Sharpless, Norman E.; Engelman, Jeffrey A.; Shapiro, Geoffrey I.; Kung, Andrew L.; Wong, Kwok-Kin

    2014-01-01

    Purpose To extend the results of a phase III trial in non-small cell lung cancer patients with adenocarcinomas harboring EML4-ALK fusion. Experimental Design we performed a co-clinical trial in a mouse model comparing the ALK inhibitor crizotinib to the standard-of-care cytotoxic agents docetaxel or pemetrexed. Results Concordant with the clinical outcome in humans, crizotinib produced a substantially higher response rate compared to chemotherapy, associated with significantly longer progression-free survival. Overall survival was also prolonged in crizotinib- compared to chemotherapy-treated mice. Pemetrexed produced superior overall survival compared to docetaxel, suggesting that this agent may be the preferred chemotherapy in the ALK population. Additionally, in the EML4-ALK-driven mouse lung adenocarcinoma model, HSP90 inhibition can overcome both primary and acquired crizotinib resistance. Furthermore, HSP90 inhibition, as well as the second-generation ALK inhibitor TAE684, demonstrated activity in newly developed lung adenocarcinoma models driven by crizotinib-insensitive EML4-ALK L1196M or F1174L. Conclusions Our findings suggest that crizotinib is superior to standard chemotherapy in ALK inhibitor-naïve disease and support further clinical investigation of HSP90 inhibitors and second-generation ALK inhibitors in tumors with primary or acquired crizotinib resistance. PMID:24327273

  12. Involvement of histamine H1 and H2 receptors in hypothermia induced by ionizing radiation in guinea pigs

    SciTech Connect

    Kandasamy, S.B.; Hunt, W.A.

    1988-01-01

    Radiation-induced hypothermia was examined in guinea pigs. Exposure to the head alone or whole-body irradiation-induced hypothermia, whereas exposure of the body alone produced a small insignificant response. Systemic injection of disodium cromoglycate (a mast cell stabilizer) and cimetidine (H2-receptor antagonist) had no effect on radiation-induced hypothermia, whereas systemic and central administration of mepyramine (H1-receptor antagonist) or central administration disodium cromoglycate or cimetidine attenuated it, indicating the involvement of central histamine through both H1 and H2 receptors in this response. Serotonin is not involved, since the serotonin antagonist methysergide had no effect on radiation-induced hypothermia. These results indicate that central histaminergic systems may be involved in radiation-induced hypothermia.

  13. Involvement of histamine H1 and H2 receptors in hypothermia induced by ionizing radiation in guinea pigs

    SciTech Connect

    Kandasamy, S.B.; Hunt, W.A.

    1988-01-01

    Radiation-induced hypothermia was examined in guinea pigs. Exposure to the head alone or whole-body irradiation induced hypothermia, whereas exposure of the body alone produced a small insignificant response. Systemic injection of disodium cromoglycate (a mast cell stabilizer) and cimetidine (H2-receptor antagonist) had no effect on radiation-induced hypothermia, whereas systemic and central administration of mepyramine (H1-receptor antagonist) or central administration of disodium cromoglycate or cimetidine attenuated it, indicating the involvement of central histamine through both H1 and H2 receptors in this response. Serotonin is not involved, since the serotonin antagonist methysergide had no effect on radiation-induced hypothermia. These results indicate that central histaminergic systems may be involved in radiation-induced hypothermia. 34 references, 5 figures, 2 tables.

  14. Inosine Triphosphatase Genetic Variants are Protective Against Anemia During Antiviral Therapy for HCV2/3 But Do Not Decrease Dose Reductions of RBV Or Increase SVR

    PubMed Central

    Thompson, Alexander J.; Santoro, Rosanna; Piazzolla, Valeria; Clark, Paul J.; Naggie, Susanna; Tillmann, Hans L.; Patel, Keyur; Muir, Andrew J.; Shianna, Kevin V.; Mottola, Leonardo; Petruzzellis, Daniela; Romano, Mario; Sogari, Fernando; Facciorusso, Domenico; Goldstein, David B.; McHutchison, John G.; Mangia, Alessandra

    2016-01-01

    Two functional variants in the inosine triphosphatase (ITPA) gene causing inosine triphos-phatase (ITPase) deficiency protect against ribavirin (RBV)-induced hemolytic anemia and the need for RBV dose reduction in patients with genotype 1 hepatitis C virus (HCV). No data are available for genotype 2/3 HCV. We evaluated the association between the casual ITPA variants and on-treatment anemia in a well-characterized cohort of genotype 2/3 patients treated with variable-duration pegylated interferon alfa-2b (PEG-IFN-α2b) and RBV. Two hundred thirty-eight Caucasian patients were included in this retrospective study [185 (78%) with genotype 2 and 53 (22%) with genotype 3]. Patients were treated with PEG-IFN-α2b plus weight-based RBV (1000/1200 mg) for 12 (n = 109) or 24 weeks (n = 129). The ITPA polymorphisms rs1127354 and rs7270101 were genotyped, and an ITPase deficiency variable was defined that combined both ITPA variants according to their effect on ITPase activity. The primary endpoint was hemoglobin (Hb) reduction in week 4. We also considered Hb reduction over the course of therapy, the need for RBV dose modification, and the rate of sustained virological response (SVR). The ITPA variants were strongly and independently associated with protection from week 4 anemia (P = 10−6 for rs1127354 and P = 10−7 for rs7270101). Combining the variants into the ITPase deficiency variable increased the strength of association (P = 10−11). ITPase deficiency protected against anemia throughout treatment. ITPase deficiency was associated with a delayed time to an Hb level < 10 g/dL (hazard ratio = 0.25, 95% confidence interval = 0.08–0.84, P = 0.025) but not with the rate of RBV dose modification (required per protocol at Hb < 9.5 g/dL). There was no association between the ITPA variants and SVR. Conclusion Two ITPA variants were strongly associated with protection against treatment-related anemia in patients with genotype 2/3 HCV, but they did not decrease the need

  15. Addicts with chronic hepatitis C: Difficult to reach, manage or treat?

    PubMed Central

    Zanini, Barbara; Benini, Federica; Pigozzi, Marie Graciella; Furba, Patrizia; Giacò, Ernesto; Cinquegrana, Antonia; Fasoli, Mariagrazia; Lanzini, Alberto

    2013-01-01

    AIM: To assess the acceptance, safety and efficacy of care and treatment for chronic hepatitis C (CHC) in drug addicts. METHODS: We designed a multidisciplinary, phase IV prospective cohort study. All illicit drug users (IDUs) visited a Territorial Addiction Service (SerT) in the District of Brescia, and hepatitis C antibody (HCVAb) testing positive were offered as part of a standardised hepatologic visit in our Gastroenterology Unit. Patients with confirmed CHC and without medical contraindications were administered peginterferon alfa-2b 1.5 μg/kg per week plus ribavirin (800-1400 mg/d) for 16-48 wk. All IDUs were unselected because of ongoing addiction and read and signed an informed consent form. Virologic responses at weeks 4 and 12 of therapy, at the end of treatment and 24 wk after the end of treatment were the main measures of efficacy. Adherence was estimated according to the 80/80/80 criteria. RESULTS: From November 2007 to December 2009, 162 HCVAb+ IDUs were identified. Sixty-seven patients (41% of the initial cohort) completed the diagnostic procedure, and CHC was diagnosed in 54 (33% of the total). Forty-nine patients were offered therapy, and 39 agreed (80% of acceptance rate). The prevalent HCV genotype was type 1, and the HCV RNA baseline level was over 5.6 log/mL in 61% of cases. Five patients dropped out, two because of severe adverse events (SAEs) and three without medical need. Twenty-three and 14 patients achieved end of treatment responses (ETRs; 59%) and sustained virologic responses (SVRs; 36%), respectively. Thirty-one patients were fully compliant with the study protocol (80% adherence). The prevalence of host and viral characteristics negatively affecting the treatment response was high: age over 40 years (54%), male gender (85%), overweight body type (36%), previous unsuccessful antiviral therapy (21%), HCV genotype and viral load (60% and 62%, respectively), earlier contact with HBV (40%) and steatosis and fibrosis (44% and 17

  16. 40 CFR 721.5279 - 2,7-Naphthalenedisulfonic acid, 4-amino-3-[[4′2-amino-4-[(3-butoxy-2-hydroxypropyl)amino]phebyl...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-amino-3- phebyl]azo]-3,3â²-dimethyl -4-yl]azo]-5-hydroxy-6-(phenylazo)-, disodium salt. 721.5279 Section... Substances § 721.5279 2,7-Naphthalenedisulfonic acid, 4-amino-3- phebyl]azo]-3,3′-dimethyl -4-yl]azo]-5... reporting. (1) The chemical substance identified as 2,7-naphthalenedisulfonic acid, 4-amino-3-...

  17. Syntheses, structures, thermal stabilities and luminescence of two new lead sulfonates with phosphonate, carboxylate and pyridine

    NASA Astrophysics Data System (ADS)

    Fu, Ruibiao; Hu, Shengmin; Wu, Xintao

    2014-05-01

    Hydrothermal reactions of Pb2+ ion with disodium 4,4'-bis(2-sulfonatostyryl)biphenyl (Na2L1), 4-pyridyl-CH2N(CH2COOH)(CH2PO3 H2) (H3L2) and 4,4'-bipyridine (4,4'-bipy) afforded two new lead sulfonates, namely, [Pb4(L1)2(HL2)2(H2O)

  18. 40 CFR 721.1660 - Benzidine-based chemical substances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-Naphthalenedisulfonic acid, 4-amino-3- -4-yl]azo]-5-hydroxy-6-(phenylazo)-, disodium salt 2302-97-8 C.I. Direct Red 44.... Direct Blue 2 22590 2,7-Naphthalenedisulfonic acid, 5-amino-3- -4-yl]azo]-4-hydroxy-, trisodium salt 2429... 2429-83-6 C.I. Direct Black 4 30245 2,7-Naphthalenedisulfonic acid, 4-amino-3-...

  19. 40 CFR 721.1660 - Benzidine-based chemical substances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-Naphthalenedisulfonic acid, 4-amino-3- -4-yl]azo]-5-hydroxy-6-(phenylazo)-, disodium salt 2302-97-8 C.I. Direct Red 44.... Direct Blue 2 22590 2,7-Naphthalenedisulfonic acid, 5-amino-3- -4-yl]azo]-4-hydroxy-, trisodium salt 2429... 2429-83-6 C.I. Direct Black 4 30245 2,7-Naphthalenedisulfonic acid, 4-amino-3-...

  20. 40 CFR 721.1660 - Benzidine-based chemical substances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-Naphthalenedisulfonic acid, 4-amino-3- -4-yl]azo]-5-hydroxy-6-(phenylazo)-, disodium salt 2302-97-8 C.I. Direct Red 44.... Direct Blue 2 22590 2,7-Naphthalenedisulfonic acid, 5-amino-3- -4-yl]azo]-4-hydroxy-, trisodium salt 2429... 2429-83-6 C.I. Direct Black 4 30245 2,7-Naphthalenedisulfonic acid, 4-amino-3-...

  1. 21 CFR 74.1322 - D&C Red No. 22.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false D&C Red No. 22. 74.1322 Section 74.1322 Food and... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1322 D&C Red No. 22. (a) Identity. (1) The color additive D&C Red No. 22 is principally the disodium salt of 2′,4′,5′7′-tetrabromofluorescein (CAS Reg. No....

  2. 21 CFR 74.1205 - D&C Green No. 5.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false D&C Green No. 5. 74.1205 Section 74.1205 Food and... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1205 D&C Green No. 5. (a) Identity. (1) The color additive D&C Green No. 5 is principally the disodium salt of 2,2′- bis- (CAS Reg. No. 4403-90-1). (2) Color...

  3. 40 CFR 721.5279 - 2,7-Naphthalenedisulfonic acid, 4-amino-3-[[4′2-amino-4-[(3-butoxy-2-hydroxypropyl)amino]phebyl...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-amino-3- phebyl]azo]-3,3â²-dimethyl -4-yl]azo]-5-hydroxy-6-(phenylazo)-, disodium salt. 721.5279 Section... Substances § 721.5279 2,7-Naphthalenedisulfonic acid, 4-amino-3- phebyl]azo]-3,3′-dimethyl -4-yl]azo]-5... reporting. (1) The chemical substance identified as 2,7-naphthalenedisulfonic acid, 4-amino-3-...

  4. 75 FR 13556 - Biocompatibles UK Ltd.; Filing of Color Additive Petition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-22

    ... acid, 1-amino-4-(3-((4,6-dichloro-s-triazin-2- yl)amino)-4-sulfoanilino)-9,10-dihydro-9,10-dioxo... regulations be amended to provide for the safe use of C.I. Reactive Blue No. 4 [2-anthracenesulfonic acid, 1-amino-4-(3-((4,6- dichloro-s-triazin-2-yl)amino)-4-sulfoanilino)-9,10-dihydro-9,10-dioxo, disodium...

  5. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false D&C Orange No. 11. 74.1261 Section 74.1261 Food... COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1261 D&C Orange No. 11. (a) Identity. (1) The color additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of...

  6. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false D&C Orange No. 11. 74.1261 Section 74.1261 Food... COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1261 D&C Orange No. 11. (a) Identity. (1) The color additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of...

  7. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false D&C Orange No. 11. 74.1261 Section 74.1261 Food... COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1261 D&C Orange No. 11. (a) Identity. (1) The color additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of...

  8. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false D&C Orange No. 11. 74.1261 Section 74.1261 Food... COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1261 D&C Orange No. 11. (a) Identity. (1) The color additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of...

  9. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false D&C Orange No. 11. 74.1261 Section 74.1261 Food... COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1261 D&C Orange No. 11. (a) Identity. (1) The color additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of...

  10. 21 CFR 74.101 - FD&C Blue No. 1.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FD&C Blue No. 1. 74.101 Section 74.101 Food and... ADDITIVES SUBJECT TO CERTIFICATION Foods § 74.101 FD&C Blue No. 1. (a) Identity. (1) The color additive FD&C Blue No. 1 is principally the disodium salt of ethyl -α-(o-sulfophenyl) benzylidene] -...

  11. Feasibility of using saturated solar ponds for brine unmixing. Final report

    SciTech Connect

    Not Available

    1980-09-30

    The overall objective of this study was to investigate in the laboratory the feasibility of using saturated solar ponds for unmixing a brine of intermediate concentration into dilute and concentrated brine streams for salinity gradient energy conversion systems. This objective was accomplished by conducting experiments on laboratory saturated ponds using borax, potassium perchlorate, potassium nitrate, disodium phosphate and potassium alum. Results from ponds using borax, potassium nitrate and disodium phosphate conclusively demonstrated that saturated solar ponds can self-generate and self-maintain a stable density gradient. Moreover, these ponds reestablished stable density profiles after the ponds were externally mixed. Based on preliminary results, the residence time for unmixing of a brine of intermediate concentration into dilute and concentrated brine streams varies from a few days for the borax pond to about two weeks for the disodium phosphate pond, depending upon the characteristics of the individual saturated solution. Because of only a very small increase in the density of saturated solutions from 25/sup 0/C to 90/sup 0/C, the potassium perchlorate pond could not establish a stable density stratification.

  12. IR spectroscopic investigation of the inhibition of the glycation process by acetylsalicylic acid

    NASA Astrophysics Data System (ADS)

    Otero de Joshi, Virginia; Gil, Herminia; Contreras, Silvia; Velasquez, William; Joshi, Narahari V.

    2000-05-01

    An IR spectroscopic study was carried out at room temperature for Human Serum albumin (HSA) glycated with fructose and glucose and inhibited with acetylsalicylic acid. The glycation process was carried out in our laboratory by a conventional method to confirm earlier reported observation of the effect of glycation on the intensity variation of the IR spectra, particularly, in the range 1500 cm-1 to 1700 cm-1 and around 3300 cm-1. IR spectra reveal that the effects of glycation of HSA by fructose are more intense than with glucose, which is the expected. Bovine serum albumin was also glycated using Glucose-6-phosphate disodium salt, and gamma-globulin was glycate with glucose, As expected, the glycation process was more intense with glucose-t-phosphate disodium salt. Acetyl salicylic acid was also used and its inhibitor effects could be observed in both cases, with glucose and with glucose-6-phosphate disodium salt even though, to a smaller extent with the latter. This is consistent with the earlier data and is explained on the basis of the attachment of macromolecules to (epsilon) -NH2 groups of lysines. The experimental results confirm that acetylsalicylic acid, indeed, acts as an inhibitor by acetylation of the (epsilon) -NG2 group where the sugars are supposed to be attached.

  13. Safety and Efficacy of Gadoxetate Disodium–Enhanced Liver MRI in Pediatric Patients Aged >2 Months to <18 Years—Results of a Retrospective, Multicenter Study

    PubMed Central

    Geller, James; Kasahara, Mureo; Martinez, Mercedes; Soresina, Annarosa; Kashanian, Fran; Endrikat, Jan

    2016-01-01

    PURPOSE To assess the safety and efficacy of gadoxetate disodium–enhanced liver MR imaging in pediatric patients. MATERIAL AND METHODS Retrospective, multicenter study including pediatric patients aged >2 months to <18 years who underwent contrast-enhanced liver MRI due to focal liver lesions. A single intravenous bolus injection of 0.025 to 0.05 mmol/kg body weight of gadoxetate disodium was administered. Adverse events (AEs) up to 24 hours after injection were recorded and a one-year follow-up was conducted for all serious and unexpected AEs. Efficacy was defined based on the additional diagnostic information obtained from the combined (pre- and postcontrast) image sets as compared with the precontrast image sets by blinded reading. RESULTS A total of 52 patients for safety and 51 patients for efficacy analyses were evaluated. Twenty-two patients (42.3%) reported a total of 51 serious AEs (SAEs) and one AE after one year. No SAE or AE was related to gadoxetate disodium injection. Gadoxetate disodium–related effects on vital signs were not seen. Additional diagnostic information was obtained for 86.3% of patients. The three most improved efficacy variables were lesion-to-background contrast, lesion characterization, and improved border delineation in 78.4%, 76.5%, and 70.6% of patients, respectively. CONCLUSION Gadoxetate disodium in pediatric patients did not raise any clinically significant safety concern. Contrast enhancement provided additional clinically relevant information. PMID:27478381

  14. FTIR and {sup 31}P-NMR spectroscopic analyses of surface species in phosphate-catalyzed lactic acid conversion

    SciTech Connect

    Gunter, G.C.; Tam, M.S.; Miller, D.J.

    1996-11-01

    The surface species present on silica/alumina-supported sodium phosphates, active catalysts for the conversion of lactic acid to acrylic acid and 2,3-pentanedione, are examined by pre- and postreaction MAS {sup 31}P-NMR and FTIR spectroscopies. Species present following lactic acid conversion are identified by transmission FTIR of phosphates supported on silicon disks (as a model catalyst system) and verified by {sup 31}P-NMR and diffuse reflectance IR spectroscopy of actual catalysts used in reaction. Monosodium phosphate (NaH{sub 2}PO{sub 4}) condenses to a mixture of sodium polyphosphate (NaPO{sub 3}){sub n} and sodium trimetaphosphate (Na{sub 3}P{sub 3}O{sub 9}), which exhibit little catalytic activity for converting lactic acid to desired products. Disodium phosphate (Na{sub 2}HPO{sub 4}) condenses to tetrasodium pyrophosphate (Na{sub 4}P{sub 2}O{sub 7}), and proton transfer from lactic acid to pyrophosphate results in the formation of sodium lactate. Trisodium phosphate (Na{sub 3}PO{sub 4}) accepts a proton from lactic acid to form sodium lactate and disodium phosphate, which condenses to pyrophosphate. The presence of pyrophosphate and sodium lactate on supported disodium and trisodium phosphates explains their similar catalytic properties; the larger quantity of sodium lactate present on trisodium phosphate leads to higher conversions at lower temperatures. 40 refs., 14 figs., 2 tabs.

  15. I. Enabling Single-Chain Surfactants to Form Vesicles by Nonamphiphilic Liquid Crystals in Water II. Controlling Attachment and Ligand-Mediated Adherence of Candida albicans on Monolayers

    NASA Astrophysics Data System (ADS)

    Varghese, Nisha

    This dissertation describes a fundamental study of weak noncovalent interactions and surface forces that exist at the interfaces of various interacting moieties (small molecules or microbes), and its relevance to colloidal and material chemistry. Chapter 1 presents an emulsion system that enables single-chain anionic or nonionic surfactants to sequester and encapsulate certain water-soluble organic salts, leading to the formation of vesicles in water. The water-soluble organic salt in the system comprises of disodium cromoglycate crystals that are emulsified by surfactants in water to form stable liquid crystal droplets. The work provides an exception to the rule of geometric packing factor that dictates formation of micelles by the surfactants in water. Chapter 2 shows that the odd or even number of carbon atoms present in the aliphatic chain of surfactants affect the ability of surfactants to emulsify aqueous-based liquid crystals of disodium cromoglycate. Such an odd-even effect is frequently observed for solid state properties like melting point, heat of fusion and refractive index but is rarely observed for molecules present in solution. When mixed in water, anionic single-chain surfactants with odd number of carbon atoms emulsifies disodium cromoglycate to form liquid crystal droplets, while surfactants with even number of carbon atoms fail to emulsify disodium cromoglycate. Chapter 3 Bolaamphiphiles usually form vesicles only in extreme conditions or in the presence of surfactants. Here, we explore the co-assembly system of synthesized bolaamphiphiles and disodium cromoglycate in water. The combination of the self-assembly forces of the bolaamphiphile and self-associating property of disodium cromoglycate liquid crystals act together at the interface form a unique microemulsion of liquid crystal droplets of disodium cromoglycate embedded in liquid crystal phase. Chapter 4 describes a key event (adhesion) that precedes infections caused by Candida albicans

  16. Medicines and the media: news reports of medicines recommended for government reimbursement in Australia

    PubMed Central

    2013-01-01

    Background Previous analyses of the listings of trastuzumab on the Australian Pharmaceutical Benefits Scheme (PBS) and HPV vaccine on the National Immunisation Program (NIP) suggest a media influence on policy makers. We examined the timing and content of Australian newspaper reports of medicines in relation to Pharmaceutical Benefits Advisory Committee (PBAC) decisions. Methods We identified newspaper reports (2005-2008) of medicines recommended for PBS listing in 2006–2007, analysing the content for mentions of the medicine, PBS and medicine costs to the patient and the government and counting the numbers of articles published in the six months before, the month of, and the six months after the relevant PBAC meeting. Case studies examined reporting for infliximab for Crohn’s Disease, pemetrexed for mesothelioma, and ADHD (Attention Deficit Hyperactivity Disorder) medicines atomoxetine and methylphenidate. Results Of 79 eligible medicines, 62 had news reports. Most often reported were HPV vaccine (1230 stories), trastuzumab (410), pemetrexed (83), botulinum toxin (71), lapatinib (65), methylphenidate (57), atomoxetine (54), infliximab (49), rotavirus vaccine (45). Eighteen medicines had ≥20 news reports (total 2350 stories); nine of these cost more than AU$10,000 per course or year of treatment. For these 18 medicines, 31% of stories appeared in the six months prior to the PBAC meeting, 14% in the meeting month and 33% in the six months post-meeting. 38% of the stories had ≥3 medicine mentions, 37% referred to the PBS, 24% to cost to the patient, and 9% cost to Government. There was active patient lobby group campaigning in support of listing of infliximab and pemetrexed; the stories for ADHD were often more negative, referring to the dangers of the medicines and sometimes questioning the appropriateness of treatment and public subsidy. There was little discussion of the PBAC’s evidence-based decision-making processes. Conclusions While there was no

  17. Recurrent "pneumonia" in left lower lobe lasting for 8 years: a case report.

    PubMed

    Yuan, Dong-Mei; Yao, Yan-Wen; Li, Qian; Liu, Chen-Yang; Li, Pei; Cao, E-Hong; Xiao, Xin-Wu; Su, Xin; Song, Yong

    2016-06-01

    Bronchioloalveolar carcinoma (BAC) is a unique lung neoplasm with variable forms, such as single nodular, multifocal and lobar pneumonic types. The pneumonic type BAC is often difficult to differentiate from pneumonia. Here we present a case of 63-year-old Chinese male, who had recurrent cough, white sputum with pneumonic lesions in left lower lobe. He suffered from lung biopsies for three times, and finally diagnosed as high differentiated adenocarcinoma 8 years later. He was treated with four cycles of pemetrexed and cisplatin, and four cycles of docetaxel and nedaplatin. However, he did not achieve disease stabilization and is still under follow up. This case suggests that, pneumonic type adenocarcinoma may radiographically and clinically resemble infectious pneumonia. Lack of fever and leukocytosis, no response to antibiotics, air bronchogram, and accompanied nodules or patches in computed tomography (CT) scans should raise suspicion about the diagnosis of pneumonia. Lung biopsy might be the only means of ruling in a diagnosis of BAC. PMID:27413717

  18. The role of interleukin-6 in malignant mesothelioma

    PubMed Central

    Abdul Rahim, Siti N.; Ho, Gwo Y.

    2015-01-01

    Malignant mesothelioma (MM) still remains a dismal disease with a median overall survival between 9-12 months. During the past decade since the introduction of the multi-folate antagonist, pemetrexed, there have been no significant advances in its systemic treatment, particularly with novel therapeutics that have exhibited varying degrees of success in other solid tumours. In recent years, the pleiotropic proinflammatory cytokine, interleukin-6 (IL-6) has emerged as a mediator of pivotal processes such as cell proliferation and chemoresistance within the mesothelioma tumour microenvironment in addition to clinical symptoms commonly witnessed in this disease. This manuscript provides a brief summary on the pathophysiology and clinical management of MM, followed by the role of IL-6 in its tumourigenesis and the rationale for utilising anti-IL-6 therapeutics alongside standard chemotherapy and targeted agents in an attempt to prolong survival. PMID:25806346

  19. Alectinib-Induced Alopecia in a Patient with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

    PubMed Central

    Koizumi, Tomonobu; Fukushima, Toshirou; Gomi, Daisuke; Kobayashi, Takashi; Sekiguchi, Nodoka; Sakamoto, Akiyuki; Sasaki, Shigeru; Mamiya, Keiko

    2016-01-01

    Alectinib, a novel alternative anaplastic lymphoma kinase (ALK) inhibitor, is highly effective against ALK-positive non-small cell lung cancer (NSCLC) and is well tolerated. Molecular targeted agents generally have little contribution to alopecia. We encountered a case of alopecia that developed gradually over 2 months after initiation of alectinib administration for the treatment of ALK-positive NSCLC. The patient had no history of alopecia in previous treatments of cisplatin + pemetrexed and crizotinib. The present case indicates that alopecia should be taken into consideration as toxicity during alectinib treatment, which could adversely affect the psychological and emotional condition and quality of life even in patients treated with specific molecular targeted agents. PMID:27194980

  20. Maintenance or non-maintenance therapy in the treatment of advanced non-small cell lung cancer: that is the question.

    PubMed

    Galetta, D; Rossi, A; Pisconti, S; Millaku, A; Colucci, G

    2010-11-01

    Lung cancer is the most common cancer worldwide with non-small cell lung cancer (NSCLC), including squamous carcinoma, adenocarcinoma and large cell carcinoma, accounting for about 85% of all lung cancer types with most of the patients presenting with advanced disease at the time of diagnosis. In this setting first-line platinum-based chemotherapy for no more than 4-6 cycles are recommended. After these cycles of treatment, non-progressing patients enter in the so called "watch and wait" period in which no further therapy is administered until there is disease progression. In order to improve the advanced NSCLC outcomes, the efficacy of further treatment in the "watch and wait" period was investigated. This is the "maintenance therapy". Recently, the results coming from randomized phase III trials investigating two new agents, pemetrexed and erlotinib, in this setting led to their registration for maintenance therapy. Here, we report and discuss these results. PMID:21129607

  1. Recurrent “pneumonia” in left lower lobe lasting for 8 years: a case report

    PubMed Central

    Yuan, Dong-Mei; Yao, Yan-Wen; Li, Qian; Liu, Chen-Yang; Li, Pei; Cao, E-Hong; Xiao, Xin-Wu; Su, Xin

    2016-01-01

    Bronchioloalveolar carcinoma (BAC) is a unique lung neoplasm with variable forms, such as single nodular, multifocal and lobar pneumonic types. The pneumonic type BAC is often difficult to differentiate from pneumonia. Here we present a case of 63-year-old Chinese male, who had recurrent cough, white sputum with pneumonic lesions in left lower lobe. He suffered from lung biopsies for three times, and finally diagnosed as high differentiated adenocarcinoma 8 years later. He was treated with four cycles of pemetrexed and cisplatin, and four cycles of docetaxel and nedaplatin. However, he did not achieve disease stabilization and is still under follow up. This case suggests that, pneumonic type adenocarcinoma may radiographically and clinically resemble infectious pneumonia. Lack of fever and leukocytosis, no response to antibiotics, air bronchogram, and accompanied nodules or patches in computed tomography (CT) scans should raise suspicion about the diagnosis of pneumonia. Lung biopsy might be the only means of ruling in a diagnosis of BAC. PMID:27413717

  2. Exon 19 L747P mutation presented as a primary resistance to EGFR-TKI: a case report

    PubMed Central

    Wang, Yu-Ting; Ning, Wei-Wei; Li, Jing

    2016-01-01

    Active mutations of the EGFR gene have been proved to predict the activity of EGFR-TKI. The most common mutations are the exon 19 deletion and exon 21 point mutation, both of which are sensitive to EGFR-TKI. However, rare EGFR mutations or complex mutations still exist, and data of which are scarce and controversial. Their response to EGFR-TKI remains uncertain. We presented a patient diagnosed with stage IV lung adenocarcinoma who was found to have the EGFR mutation in exon 19 (L747P) before any treatment. The disease progressed 2 months after the chemotherapy containing cisplatin and pemetrexed, and erlotinib was administered, but there was no response found. This EGFR-TKI naïve patient failed to achieve the desired effect with the therapy of EGFR-TKI. L747P may be associated with primary resistance to EGFR-TKI in this case. PMID:27499993

  3. Lung cancer drug therapy in Hungary – 3-year experience

    PubMed Central

    Moldvay, Judit; Rokszin, György; Abonyi-Tóth, Zsolt; Katona, Lajos; Fábián, Katalin; Kovács, Gábor

    2015-01-01

    Hungary is a world leader in lung cancer deaths, so it is of crucial importance that patients have access to modern treatments. The aim of our analysis was to explore how drug treatments are used in Hungary and how they are compatible with international practice. The inpatient and prescription database of the National Health Insurance Fund Administration of Hungary was used to study the frequency of certain chemotherapy protocols and duration of therapies during a 3-year period (2008–2010). During the study period, 12,326 lung cancer patients received first-line chemotherapy, a third of those (n=3,791) received second-line treatment, and a third of the latter (n=1,174) received third-line treatment. The average treatment duration was between 3 and 4 months. The first-line treatment of non-small-cell lung carcinoma mainly consisted of platinum treatment in combination with third-generation cytotoxic agents. A downward trend of gemcitabine, still the most common combination compound, was observed, in parallel with a significantly increased use of paclitaxel, and as a consequence carboplatin replaced cisplatin. Among the new agents, the use of pemetrexed and bevacizumab increased. Pemetrexed appeared mainly in second-line treatment, while erlotinib appeared also in second-line but mostly in third-line treatments. The first-line treatment of small-cell lung carcinoma consisted of a platinum–etoposide combination, while in the second-line setting topotecan was the most commonly used drug. According to our results, the chemotherapeutic combinations and sequencing are in accordance with international and national recommendations. Further detailed analysis of the available data may help to obtain a more accurate picture of the efficacy of lung cancer treatments as well. PMID:25999737

  4. Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study

    PubMed Central

    Morrow, C. J.; Trapani, F.; Metcalf, R. L.; Bertolini, G.; Hodgkinson, C. L.; Khandelwal, G.; Kelly, P.; Galvin, M.; Carter, L.; Simpson, K. L.; Williamson, S.; Wirth, C.; Simms, N.; Frankliln, L.; Frese, K. K.; Rothwell, D. G.; Nonaka, D.; Miller, C. J.; Brady, G.; Blackhall, F. H.; Dive, C.

    2016-01-01

    Background Over the past decade, numerous reports describe the generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling and preclinical drug testing, the requirement of a tissue biopsy limits the available patient population, particularly those with advanced oligometastatic disease. Conversely, ‘liquid biopsies’ such as circulating tumour cells (CTCs) are minimally invasive and easier to obtain. Here, we present a clinical case study of a NSCLC patient with advanced metastatic disease, a never smoker whose primary tumour was EGFR and ALK wild-type. We demonstrate for the first time, tumorigenicity of their CTCs to generate a patient CTC-derived eXplant (CDX). Patients and methods CTCs were enriched at diagnosis and again 2 months later during disease progression from 10 ml blood from a 48-year-old NSCLC patient and implanted into immunocompromised mice. Resultant tumours were morphologically, immunohistochemically, and genetically compared with the donor patient's diagnostic specimen. Mice were treated with cisplatin and pemetrexed to assess preclinical efficacy of the chemotherapy regimen given to the donor patient. Results The NSCLC CDX expressed lung lineage markers TTF1 and CK7 and was unresponsive to cisplatin and pemetrexed. Examination of blood samples matched to that used for CDX generation revealed absence of CTCs using the CellSearch EpCAM-dependent platform, whereas size-based CTC enrichment revealed abundant heterogeneous CTCs of which ∼80% were mesenchymal marker vimentin positive. Molecular analysis of the CDX, mesenchymal and epithelial CTCs revealed a common somatic mutation confirming tumour origin and showed CDX RNA and protein profiles consistent with the predominantly mesenchymal phenotype. Conclusions This study shows that the absence of NSCLC CTCs detected by CellSearch (EpCAM+) does not preclude CDX generation

  5. Chemotherapeutic-Induced Apoptosis – A Phenotype for Pharmacogenomics Studies

    PubMed Central

    Wen, Yujia; Gorsic, Lidija K.; Wheeler, Heather E.; Ziliak, Dana M.; Huang, R. Stephanie; Dolan, M. Eileen

    2011-01-01

    Lymphoblastoid cell lines have been used as a model system to identify genetic determinants of chemotherapeutic-induced cytotoxicity, a phenotype thought to represent cellular sensitivity to drug. However, cytotoxicity is a broad measurement encompassing cell cycle inhibition as well as cell death (apoptotic and non-apoptotic). We evaluated caspase 3/7 mediated cellular apoptosis with six chemotherapeutic agents: 5′-deoxy-fluorouridine, pemetrexed, cytarabine, paclitaxel, carboplatin and cisplatin. Using monozygotic twin pair and sibling pair lymphoblastoid cell lines, we identified conditions for measurement of caspase activity. Although treatment with 5′-deoxy-fluorouridine and pemetrexed for up to 24 h did not result in significant apoptosis or inter-individual variation in caspase dependent cell death; paclitaxel, cisplatin, carboplain and cytarabine treatment for 24 h resulted in 9.4, 9.1, 7.0 and 6.0 fold increases in apoptosis relative to control, respectively. There was a weak correlation between caspase activity and cytotoxicity (r2=0.03 to 0.29) demonstrating that cytotoxicity and apoptosis are two distinct phenotypes that may produce independent genetic associations. Estimated heritability (h2) for apoptosis was 0.57 and 0.29 for cytarabine (5 μM and 40 μM respectively), 0.22 for paclitaxel (12.5 nM), and 0.34 for cisplatin (5 μM). The HapMap CEU panel of lymphoblastoid cell lines (n = 77) were evaluated for sensitivity to cisplatin followed by genome wide association studies with over 2 million SNPs at p < 0.001. We identified a significant enrichment of cisplatin-induced apoptosis SNPs within the significant cisplatin induced cytotoxicity SNPs and an enrichment of expression quantitative trait loci. PMID:21642893

  6. Role of the tryptophan residues in proton-coupled folate transporter (PCFT-SLC46A1) function.

    PubMed

    Najmi, Mitra; Zhao, Rongbao; Fiser, Andras; Goldman, I David

    2016-07-01

    The proton-coupled folate transporter (PCFT) mediates folate absorption across the brush-border membrane of the proximal small intestine and is required for folate transport across the choroid plexus into the cerebrospinal fluid. In this study, the functional role and accessibility of the seven PCFT Trp residues were assessed by the substituted-cysteine accessibility method. Six Trp residues at a lipid-aqueous interface tolerated Cys substitution in terms of protein stability and function. W85C, W202C, and W213C were accessible to N-biotinyl aminoethylmethanethiosulfonate; W48C and W299C were accessible only after treatment with dithiotreitol (DTT), consistent with modification of these residues by an endogenous thiol-reacting molecule and their extracellular location. Neither W107C nor W333C was accessible (even after DTT) consistent with their cytoplasmic orientation. Biotinylation was blocked by pemetrexed only for the W48C (after DTT), W85C, W202C residues. Function was impaired only for the W299C PCFT mutant located in the 4th external loop between the 7th and 8th transmembrane helices. Despite its aqueous location, function could only be fully preserved with Phe and, to a lesser extent, Ala substitutions. There was a 6.5-fold decrease in the pemetrexed influx Vmax and a 3.5- and 6-fold decrease in the influx Kt and Ki, respectively, for the W299S PCFT. The data indicate that the hydrophobicity of the W299 residue is important for function suggesting that during the transport cycle this residue interacts with the lipid membrane thereby impacting on the oscillation of the carrier and, indirectly, on the folate binding pocket. PMID:27251438

  7. Role of the fourth transmembrane domain in proton-coupled folate transporter function as assessed by the substituted cysteine accessibility method.

    PubMed

    Shin, Daniel Sanghoon; Zhao, Rongbao; Fiser, Andras; Goldman, I David

    2013-06-15

    The proton-coupled folate transporter (PCFT, SLC46A1) mediates folate transport across the apical brush-border membrane of the proximal small intestine and the basolateral membrane of choroid plexus ependymal cells. Two loss-of-function mutations in PCFT, which are the basis for hereditary folate malabsorption, have been identified within the fourth transmembrane domain (TMD4) in subjects with this disorder. We have employed the substituted Cys accessibility method (SCAM) to study the accessibilities of all residues in TMD4 and their roles in folate substrate binding to the carrier. When residues 146-167 were replaced by Cys, all except R148C were expressed at the cell surface. Modification of five of these substituted Cys residues (positions 147, 152, 157, 158, and 161) by methanethiosulfonate (MTS) reagents led to reduction of PCFT function. All five residues could be labeled with N-biotinylaminoethyl-MTS, and this could be blocked by the high-affinity PCFT substrate pemetrexed. Pemetrexed also protected PCFT mutant function from inhibitory modification of the substituted Cys at positions 157, 158, and 161 by a MTS. The findings indicate that these five residues in TMD4 are accessible to the aqueous translocation pathway, play a role in folate substrate binding, and are likely located within or near the folate binding pocket. A homology model of PCFT places three of these residues, Phe¹⁵⁷, Gly¹⁵⁸, and Leu¹⁶¹, within a breakpoint in the midportion of TMD4, a region that likely participates in alterations in the PCFT conformational state during carrier cycling. PMID:23552283

  8. Synergistic anti-tumor efficacy of immunogenic adenovirus ONCOS-102 (Ad5/3-D24-GM-CSF) and standard of care chemotherapy in preclinical mesothelioma model.

    PubMed

    Kuryk, Lukasz; Haavisto, Elina; Garofalo, Mariangela; Capasso, Cristian; Hirvinen, Mari; Pesonen, Sari; Ranki, Tuuli; Vassilev, Lotta; Cerullo, Vincenzo

    2016-10-15

    Malignant mesothelioma (MM) is a rare cancer type caused mainly by asbestos exposure. The median overall survival time of a mesothelioma cancer patient is less than 1-year from diagnosis. Currently there are no curative treatment modalities for malignant mesothelioma, however treatments such as surgery, chemotherapy and radiotherapy can help to improve patient prognosis and increase life expectancy. Pemetrexed-Cisplatin is the only standard of care (SoC) chemotherapy for malignant mesothelioma, but the median PFS/OS (progression-free survival/overall survival) from the initiation of treatment is only up to 12 months. Therefore, new treatment strategies against malignant mesothelioma are in high demand. ONCOS-102 is a dual targeting, chimeric oncolytic adenovirus, coding for human GM-CSF. The safety and immune activating properties of ONCOS-102 have already been assessed in phase 1 study (NCT01598129). In this preclinical study, we evaluated the antineoplastic activity of combination treatment with SoC chemotherapy (Pemetrexed, Cisplatin, Carboplatin) and ONCOS-102 in xenograft BALB/c model of human malignant mesothelioma. We demonstrated that ONCOS-102 is able to induce immunogenic cell death of human mesothelioma cell lines in vitro and showed anti-tumor activity in the treatment of refractory H226 malignant pleural mesothelioma (MPM) xenograft model. While chemotherapy alone showed no anti-tumor activity in the mesothelioma mouse model, ONCOS-102 was able to slow down tumor growth. Interestingly, a synergistic anti-tumor effect was seen when ONCOS-102 was combined with chemotherapy regimens. These findings give a rationale for the clinical testing of ONCOS-102 in combination with first-line chemotherapy in patients suffering from malignant mesothelioma. PMID:27287512

  9. Mechanism of airway hyperresponsiveness to adenosine induced by allergen challenge in actively sensitized Brown Norway rats

    PubMed Central

    Hannon, J P; Tigani, B; Williams, I; Mazzoni, L; Fozard, J R

    2001-01-01

    We have explored the role of allergen sensitization and challenge in defining the response of the airways of the Brown Norway (BN) rat to adenosine. In naïve animals or in rats sensitized to ovalbumin (OA) adenosine induced only weak bronchoconstrictor responses. Challenge of sensitized animals with OA induced a marked airway hyperresponsiveness to adenosine which was not seen with methacholine or bradykinin. The augmented bronchoconstrictor response to adenosine was not affected by acute bivagotomy or atropine nor mimicked by an i.v. injection of capsaicin. It was, however, blocked selectively by disodium cromoglycate methysergide or ketanserin and reduced in animals treated sub-chronically with compound 48/80. The augmented response to adenosine was associated with increases in the plasma concentrations of both histamine and 5-hydroxytryptamine (5-HT), which were attenuated by pretreatment with disodium cromoglycate, and degranulation of mast cells in the lung. Parenchymal strips from lungs removed from sensitized rats challenged with OA gave augmented bronchoconstrictor responses to adenosine relative to strips from sensitized animals challenged with saline. Responses were inhibited by methysergide and disodium cromoglycate. These data demonstrate a marked augmentation of the bronchoconstrictor response to adenosine in actively sensitized BN rats challenged with OA. The augmented response is primarily a consequence of mast cell activation, leading to the release of 5-HT, which in turn induces bronchoconstriction. Our data further suggest the involvement of a discrete lung-based population of mast cells containing and releasing mainly 5-HT and brought into play by prior exposure to allergen. PMID:11264245

  10. Calorimetric and Diffractometric Evidence for the Sequential Crystallization of Buffer Components and the Consequential pH Swing in Frozen Solutions

    SciTech Connect

    Sundaramurthi, Prakash; Shalaev, Evgenyi; Suryanarayanan, Raj

    2010-06-22

    Sequential crystallization of succinate buffer components in the frozen solution has been studied by differential scanning calorimetry and X-ray diffractometry (both laboratory and synchrotron sources). The consequential pH shifts were monitored using a low-temperature electrode. When a solution buffered to pH < pK{sub a2} was cooled from room temperature (RT), the freeze-concentrate pH first increased and then decreased. This was attributed to the sequential crystallization of succinic acid, monosodium succinate, and finally disodium succinate. When buffered to pH > pK{sub a2}, the freeze-concentrate pH first decreased and then increased due to the sequential crystallization of the basic (disodium succinate) followed by the acidic (monosodium succinate and succinic acid) buffer components. XRD provided direct evidence of the crystallization events in the frozen buffer solutions, including the formation of disodium succinate hexahydrate [Na{sub 2}(CH{sub 2}COO){sub 2} {center_dot} 6H{sub 2}O]. When the frozen solution was warmed in a differential scanning calorimeter, multiple endotherms attributable to the melting of buffer components and ice were observed. When the frozen solutions were dried under reduced pressure, ice sublimation was followed by dehydration of the crystalline hexahydrate to a poorly crystalline anhydrate. However, crystalline succinic acid and monosodium succinate were retained in the final lyophiles. The pH and the buffer salt concentration of the prelyo solution influenced the crystalline salt content in the final lyophile. The direction and magnitude of the pH shift in the frozen solution depended on both the initial pH and the buffer concentration. In light of the pH-sensitive nature of a significant fraction of pharmaceuticals (especially proteins), extreme care is needed in both the buffer selection and its concentration.

  11. Ultra-Rapid Absorption of Recombinant Human Insulin Induced by Zinc Chelation and Surface Charge Masking

    PubMed Central

    Pohl, Roderike; Hauser, Robert; Li, Ming; De Souza, Errol; Feldstein, Robert; Seibert, Richard; Ozhan, Koray; Kashyap, Nandini; Steiner, Solomon

    2012-01-01

    Background In order to enhance the absorption of insulin following subcutaneous injection, excipients were selected to hasten the dissociation rate of insulin hexamers and reduce their tendency to reassociate postinjection. A novel formulation of recombinant human insulin containing citrate and disodium ethylenediaminetetraacetic acid (EDTA) has been tested in clinic and has a very rapid onset of action in patients with diabetes. In order to understand the basis for the rapid insulin absorption, in vitro experiments using analytical ultracentrifugation, protein charge assessment, and light scattering have been performed with this novel human insulin formulation and compared with a commercially available insulin formulation [regular human insulin (RHI)]. Method Analytical ultracentrifugation and dynamic light scattering were used to infer the relative distributions of insulin monomers, dimers, and hexamers in the formulations. Electrical resistance of the insulin solutions characterized the overall net surface charge on the insulin complexes in solution. Results The results of these experiments demonstrate that the zinc chelating (disodium EDTA) and charge-masking (citrate) excipients used in the formulation changed the properties of RHI in solution, making it dissociate more rapidly into smaller, charge-masked monomer/dimer units, which are twice as rapidly absorbed following subcutaneous injection than RHI (Tmax 60 ± 43 versus 120 ± 70 min). Conclusions The combination of rapid dissociation of insulin hexamers upon dilution due to the zinc chelating effects of disodium EDTA followed by the inhibition of insulin monomer/dimer reassociation due to the charge-masking effects of citrate provides the basis for the ultra-rapid absorption of this novel insulin formulation. PMID:22920799

  12. Organic salt-assisted liquid-phase exfoliation of graphite to produce high-quality graphene

    NASA Astrophysics Data System (ADS)

    Du, Wencheng; Lu, Jie; Sun, Peipei; Zhu, Yinyan; Jiang, Xiaoqing

    2013-05-01

    Certain ordinary organic salts, such as edetate disodium, sodium tartrate, potassium sodium tartrate and sodium citrate were found to have universal and efficient assistant effect for liquid-phase exfoliation of graphite in common organic solvents to produce pristine graphene. Up to 123 times enhanced exfoliation efficiency was observed when sodium citrate was introduced into an exfoliation system consisting of natural graphite powder and dimethyl sulfoxide. TEM, AFM, Raman spectroscopy, EDX, TGA, and FTIR analysis showed graphite was successfully exfoliated into single or few-layer graphene nanosheets which were free of defects and oxides. The method is simple, effective, safe and economical.

  13. Red-green-blue laser emissions from dye-doped poly(vinyl alcohol) films.

    PubMed

    Yap, Seong-Shan; Siew, Wee-Ong; Tou, Teck-Yong; Ng, Seik-Weng

    2002-03-20

    A microscope slide acting as a passive waveguide was coated by three separate poly(vinyl alcohol) films that were doped with Coumarin 460, Disodium Fluorescein, and Rhodamine 640 perchlorate. On collinear pumping by a nitrogen laser, these dyes furnished primary red-green-blue laser emissions that were collected and waveguided by the microscope slide but exited from both ends. Frosting the waveguide exit introduced light scattering at the glass-air interface and spatially overlaid the red-green-blue laser emissions that emerged as a uniform white-light beam. PMID:11921803

  14. In vitro inhibition of hyaluronidase by sodium copper chlorophyllin complex and chlorophyllin analogs

    PubMed Central

    McCook, John P; Dorogi, Peter L; Vasily, David B; Cefalo, Dustin R

    2015-01-01

    Background Inhibitors of hyaluronidase are potent agents that maintain hyaluronic acid homeostasis and may serve as anti-aging, anti-inflammatory, and anti-microbial agents. Sodium copper chlorophyllin complex is being used therapeutically as a component in anti-aging cosmeceuticals, and has been shown to have anti-hyaluronidase activity. In this study we evaluated various commercial lots of sodium copper chlorophyllin complex to identify the primary small molecule constituents, and to test various sodium copper chlorophyllin complexes and their small molecule analog compounds for hyaluronidase inhibitory activity in vitro. Ascorbate analogs were tested in combination with copper chlorophyllin complexes for potential additive or synergistic activity. Materials and methods For hyaluronidase activity assays, dilutions of test materials were evaluated for hydrolytic activity of hyaluronidase by precipitation of non-digested hyaluronate by measuring related turbidity at 595 nm. High-performance liquid chromatography and mass spectroscopy was used to analyze and identify the primary small molecule constituents in various old and new commercial lots of sodium copper chlorophyllin complex. Results The most active small molecule component of sodium copper chlorophyllin complex was disodium copper isochlorin e4, followed by oxidized disodium copper isochlorin e4. Sodium copper chlorophyllin complex and copper isochlorin e4 disodium salt had hyaluronidase inhibitory activity down to 10 µg/mL. The oxidized form of copper isochlorin e4 disodium salt had substantial hyaluronidase inhibitory activity at 100 µg/mL but not at 10 µg/mL. Ascorbate derivatives did not enhance the hyaluronidase inhibitory activity of sodium copper chlorophyllin. Copper isochlorin e4 analogs were always the dominant components of the small molecule content of the commercial lots tested; oxidized copper isochlorin e4 was found in increased concentrations in older compared to newer lots tested

  15. Automatic photometric titrations of calcium and magnesium in carbonate rocks

    USGS Publications Warehouse

    Shapiro, L.; Brannock, W.W.

    1955-01-01

    Rapid nonsubjective methods have been developed for the determination of calcium and magnesium in carbonate rocks. From a single solution of the sample, calcium is titrated directly, and magnesium is titrated after a rapid removal of R2O3 and precipitation of calcium as the tungstate. A concentrated and a dilute solution of disodium ethylenediamine tetraacetate are used as titrants. The concentrated solution is added almost to the end point, then the weak solution is added in an automatic titrator to determine the end point precisely.

  16. Antibiotic Adjuvant Therapy for Multi-Drug Resistant Carbapenemases Producing Klebsiella pneumoniae Associated Sepsis: A Case Study

    PubMed Central

    2016-01-01

    Rising resistance and spread of K. pneumoniae strains, create great concerns in treating sepsis patients due to high incidence of mortality and morbidity. The current study is a case of a 20-year-old male with sepsis and bilateral lung lesions infected with Multi-Drug Resistant (MDR) carbapenemase producing K. pneumoniae (KPC) showing resistance to carbapenem and polymyxin. Based on sensitivity report, patient was put on antibiotic adjuvant: Elores (ceftriaxone, sulbactam, disodium edetate) along with fluconazole for 10 days. Elores was instituted with remarkable recovery and patient was discharged. PMID:27190808

  17. AFRRI (Armed Forces Radiobiology Research Institute) reports, January, February and March 1988. Technical report

    SciTech Connect

    Not Available

    1988-05-01

    A possible mechanism by which disodium cromoglycate (DSCG) prevents a decrease in regional cerebral blood flow but not hypotension in primates following whole body gamma irradiation was studied. Several studies have implicated superoxide radicals in intestinal and cerebral vascular disorders following ischemia and ionizing radiation, respectively, The superoxide radical is formed during radiolysis in the reaction between hydrated electrons and dissolved oxygen. For this reason, the efficiency of DSCG to scavenge hydrated electrons and possibly prevent the formation of the superoxide radical was studied. The results show that DSCG is an efficient hydrated-electrons scavenger and may effectively compete with oxygen for hydrated electrons preventing the radiolytic formation of the superoxide radicals.

  18. Polyimides containing pendent trifluoromethyl groups

    NASA Technical Reports Server (NTRS)

    Havens, S. J.; Hergenrother, P. M.

    1993-01-01

    Several new polyimides containing trifluoromethyl groups were prepared from the reaction of various aromatic dianhydrides and two new diamines containing trifluoromethyl groups, 4,4'-bis(3-amino-5-trifluoromethylphenoxy)biphenyl and l,4-bis(3-amino-5-trifluoromethylphenoxy)benzene. The diamines were prepared from the aromatic nucleophilic displacement of the disodium salts of 4,4'-biphenol or hydroquinone with 3,5-dinitrobenzotrifluoride followed by hydrogenation of the resultant dinitro compounds. The thermally cured polyimides exhibited glass transition temperatures between 186 and 262 C. By thermogravimetric analysis, the polyimides exhibited 5 percent weight losses at 484-527 C in nitrogen and 452-506 C in air.

  19. Antibiotic Adjuvant Therapy for Multi-Drug Resistant Carbapenemases Producing Klebsiella pneumoniae Associated Sepsis: A Case Study.

    PubMed

    Gupta, Robin

    2016-04-01

    Rising resistance and spread of K. pneumoniae strains, create great concerns in treating sepsis patients due to high incidence of mortality and morbidity. The current study is a case of a 20-year-old male with sepsis and bilateral lung lesions infected with Multi-Drug Resistant (MDR) carbapenemase producing K. pneumoniae (KPC) showing resistance to carbapenem and polymyxin. Based on sensitivity report, patient was put on antibiotic adjuvant: Elores (ceftriaxone, sulbactam, disodium edetate) along with fluconazole for 10 days. Elores was instituted with remarkable recovery and patient was discharged. PMID:27190808

  20. Pharmacology of Nasal Medications: An Update

    PubMed Central

    Martin, G. F.

    1988-01-01

    The author of this article reviews the pharmacology of nasal medication, focusing on the indications and side-effects. The newer group of non-sedating antihistamines proves to be a useful supplement to disodium cromoglycate and the traditional antihistamines in the treatment of allergic rhinitis. The topical steroids (flunisolide and beclomethasone dipropionate) did not produce a significant incidence of adrenal suppression, mucosal atrophy, or nasal candidiasis. The anticholinergic ipatropium bromide shows promise in the treatment of rhinorrhea. The author also reviews the use of decongestants and emollients and remarks on the factors that affect patient compliance when nasal medications are prescribed. PMID:20469495

  1. Fluorinated aromatic diamine

    NASA Technical Reports Server (NTRS)

    Jones, Robert J. (Inventor); O'Rell, Michael K. (Inventor); Hom, Jim M. (Inventor)

    1980-01-01

    This invention relates to a novel aromatic diamine and more particularly to the use of said diamine for the preparation of thermally stable high-molecular weight polymers including, for example, polyamides, polyamideimides, polyimides, and the like. This diamine is obtained by reacting a stoichometric amount of a disodium salt of 2,2-bis(4-hydroxyphenyl) hexafluoropropane with 4-chloronitrobenzene to obtain an intermediate, 2,2-bis[4-(4-nitrophenoxy)phenyl] hexafluoropropane, which is reduced to the corresponding 2,2-bis[4-(4-aminophenoxy)phenyl] hexafluoropropane.

  2. Comparison of methods for determining DNase and phosphatase activities of staphylococci.

    PubMed Central

    Langlois, B E; Harmon, R J; Akers, K; Aaron, D K

    1989-01-01

    A greater percentage of DNase-positive strains was detected with DNase test agar than with DNase test agar containing 0.005% methyl green or 0.005% toluidine blue (P less than 0.01). No significant differences were obtained in the percentage of phosphatase-positive strains with the four methods compared. On the basis of ease of use, P agar containing para-nitrophenylphosphate disodium (0.495 mg/ml) would be the preferred method for determining phosphatase activity of staphylococci. PMID:2545741

  3. Polyimides prepared from perfluoroisopropylidene diamine

    NASA Technical Reports Server (NTRS)

    Jones, Robert J. (Inventor); O'Rell, Michael K. (Inventor); Hom, Jim M. (Inventor)

    1978-01-01

    This invention relates to a novel aromatic diamine and more particularly to the use of said diamine for the preparation of thermally stable high-molecular weight polymers including, for example, polyamides, polyamideimides, polyimides, and the like. This diamine is obtained by reacting a stoichometric amount of a disodium salt of 2,2-bis(4-hydroxyphenyl) hexafluoropropane with 4-chloronitrobenzene to obtain an intermediate, 2,2-bis[4-(4-nitrophenoxy)phenyl] hexafluoropropane, which is reduced to the corresponding 2,2-bis[4-(4-aminophenoxy)phenyl] hexafluoropropane.

  4. Conductance Studies of Aqueous Succinic Acid

    NASA Astrophysics Data System (ADS)

    Apelblat, Alexander; Barthel, Josef

    1992-03-01

    Conductance measurements of aqueous solutions of succinic acid and of di-sodium succinate were performed from 278.15 to 308.15 K and the limiting conductances λ0 (1/2 Succ2- ) are reported. The Waiden product is independent of temperature: λ0(1/2 Succ2-)*η(T) = 0.503 ± 0.001. The salt conductances closely obey the Onsager limiting law. The evaluation of the equilibrium constants for the primary and secondary steps of dissociation, K1 and K2, and the limiting conductances of the hydrosuccinate ion, λ0(HSucc-), are discussed using the Quint and Viallard conductance equation

  5. Syntheses, structures, thermal stabilities and luminescence of two new lead sulfonates with phosphonate, carboxylate and pyridine

    SciTech Connect

    Fu, Ruibiao Hu, Shengmin; Wu, Xintao

    2014-05-01

    Hydrothermal reactions of Pb{sup 2+} ion with disodium 4,4'-bis(2-sulfonatostyryl)biphenyl (Na{sub 2}L1), 4-pyridyl-CH{sub 2}N(CH{sub 2}COOH)(CH{sub 2}PO{sub 3} H{sub 2}) (H{sub 3}L2) and 4,4'-bipyridine (4,4'-bipy) afforded two new lead sulfonates, namely, [Pb{sub 4}(L1){sub 2}(HL2){sub 2}(H{sub 2}O)

  6. Incorporation of radionuclides into mineral phases via a thermally unstable complexant ligand

    SciTech Connect

    Apblett, A.W.; Georgieva, G.D.; Mague, J.T.

    1993-12-31

    The complexation and thermal behavior of pyruvic acid oxime (PAO) with representative cations associated with nuclear reprocessing waste has been investigated. This ligand has the dual advantage that it precipitates most of the cations from solution and these complexes decompose at ca. 150{degrees}C to CO{sub 2}, acetonitrile, and, initially, the metal hydroxide. Introduction of the appropriate elements required for Synroc phases to a simulated waste stream followed by NaPAO and disodium fumarate leads to precipitation of a metalorganic Synroc precursor in which the components have been intimately mixed at the molecular level. This approach circumvents incorporation of alkali metals in the final ceramic.

  7. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-06-01

    , fluvastatin sodium, fondaparinux sodium; Gaboxadol, gamma-hydroxybutyrate sodium, gefitinib, gelclair, gemcitabine, gemfibrozil, glibenclamide, glyminox; Haloperidol, heparin sodium, HPV 16/HPV 18 vaccine, human insulin, human insulin; Icatibant, imatinib mesylate, indium 111 (111In) ibritumomab tiuxetan, infliximab, INKP-100, iodine (I131) tositumomab, IoGen, ipratropium bromide, ixabepilone; L-870810, lamivudine, lapatinib, laquinimod, latanoprost, levonorgestrel, licochalcone a, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, lorazepam, lovastatin; Maraviroc, maribavir, matuzumab, MDL-100907, melphalan, methotrexate, methylprednisolone, mitomycin, mitoxantrone hydrochloride, MK-0431, MN-001, MRKAd5 HIV-1 gag/pol/nef, MRKAd5gag, MVA.HIVA, MVA-BN Nef, MVA-Muc1-IL-2, mycophenolate mofetil; Nelfinavir mesilate, nesiritide, NSC-330507; Olanzapine, olmesartan medoxomil, omalizumab, oral insulin, osanetant; PA-457, paclitaxel, paroxetine, paroxetine hydrochloride, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, perillyl alcohol, pexelizumab, pimecrolimus, pitavastatin calcium, porfiromycin, prasterone, prasugrel, pravastatin sodium, prednisone, pregabalin, prinomastat, PRO-2000, propofol, prostate cancer vaccine; Rasagiline mesilate, rhBMP-2/ACS, rhBMP-2/BCP, rhC1, ribavirin, rilpivirine, ritonavir, rituximab, Ro-26-9228, rosuvastatin calcium, rosuvastatin sodium, rubitecan; Selodenoson, simvastatin, sirolimus, sitaxsentan sodium, sorafenib, SS(dsFv)-PE38, St. John's Wort extract, stavudine; Tacrolimus, tadalafil, tafenoquine succinate, talaglumetad, tanomastat, taxus, tegaserod maleate, telithromycin, tempol, tenofovir, tenofovir disoproxil fumarate, testosterone enanthate, TH-9507, thalidomide, tigecycline, timolol maleate, tiotropium bromide, tipifarnib, torcetrapib, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Valdecoxib, vardenafil hydrochloride hydrate, varenicline, VEGF-2 gene therapy, venlafaxine hydrochloride

  8. Studies of levels of biogenic amines in meat samples in relation to the content of additives.

    PubMed

    Jastrzębska, Aneta; Kowalska, Sylwia; Szłyk, Edward

    2016-01-01

    The impact of meat additives on the concentration of biogenic amines and the quality of meat was studied. Fresh white and red meat samples were fortified with the following food additives: citric and lactic acids, disodium diphosphate, sodium nitrite, sodium metabisulphite, potassium sorbate, sodium chloride, ascorbic acid, α-tocopherol, propyl 3,4,5-trihydroxybenzoate (propyl gallate) and butylated hydroxyanisole. The content of spermine, spermidine, putrescine, cadaverine, histamine, tyramine, tryptamine and 2-phenylethylamine was determined by capillary isotachophoretic methods in meat samples (fresh and fortified) during four days of storage at 4°C. The results were applied to estimate the impact of the tested additives on the formation of biogenic amines in white and red meat. For all tested meats, sodium nitrite, sodium chloride and disodium diphosphate showed the best inhibition. However, cadaverine and putrescine were characterised by the biggest changes in concentration during the storage time of all the additives. Based on the presented data for the content of biogenic amines in meat samples analysed as a function of storage time and additives, we suggest that cadaverine and putrescine have a significant impact on meat quality. PMID:26515667

  9. Planar anchoring strength and pitch measurements in achiral and chiral chromonic liquid crystals using 90-degree twist cells.

    PubMed

    McGinn, Christine K; Laderman, Laura I; Zimmermann, Natalie; Kitzerow, Heinz-S; Collings, Peter J

    2013-12-01

    Chromonic liquid crystals are formed by molecules that spontaneously assemble into anisotropic structures in water. The ordering unit is therefore a molecular assembly instead of a molecule as in thermotropic liquid crystals. Although it has been known for a long time that certain dyes, drugs, and nucleic acids form chromonic liquid crystals, only recently has enough knowledge been gained on how to control their alignment so that studies of their fundamental liquid crystal properties can be performed. In this article, a simple method for producing planar alignment of the nematic phase in chromonic liquid crystals is described, and this in turn is used to create twisted nematic structures of both achiral and chiral chromonic liquid crystals. The optics of 90-degree twist cells allows the anchoring strength to be measured in achiral systems, which for this alignment technique is quite weak, about 3×10(-7) J/m(2) for both disodium cromoglycate and Sunset Yellow FCF. The addition of a chiral amino acid to the system causes the chiral nematic phase to form, and similar optical measurements in 90-degree twist cells produce a measurement of the intrinsic pitch of the chiral nematic phase. From these measurements, the helical twisting power for L-alanine is found to be (1.1±0.4)×10(-2) μm(-1) wt%(-1) for 15 wt% disodium cromoglycate. PMID:24483474

  10. Photochemical and biological degradation of water-soluble FWAs.

    PubMed

    Guglielmetti, L

    1975-01-01

    A study was made of the photochemical and biological degradation of two water-soluble fluorescent whitening agents (FWAs): the disodium 4,4'-bis(2-sulfostyryl)-biphenyl (1) and the disodium 4,4-bis ([4-anilino-6-(N-methyl-N-2-hydroxyethyl)amino 1,3,5-triazin-2-yl]amino)stilbene-2,2'-disulfonate (2). Each represents an important class of detergent fluorescent whitening agents. The photochemical degradation of (1) was studied by irradiating diluted aqueous solutions of this compound with a low intensity high pressure mercury vapor lamp. From the intermediate, as well as the ultimate photodegradation products isolated, it can be infered that photodegradation of (1) followed the proposed scheme. The biologica degradation of (1) and (2) by activated sludge under aerobic conditions was studied using equipment similar to that proposed by the OECD for determining the biodegradation of anionic synthetic surface active agents. Under the conditons applied, both FWAs were slowly biodegraded, within 30 days, whereas the photodegradation products of (1) were completely biodegraded within 14 days. PMID:6265

  11. Zosyn® (piperacillin/tazobactam) reformulation: Expanded compatibility and coadministration with lactated Ringer’s solutions and selected aminoglycosides

    PubMed Central

    Desai, Narendra R; Shah, Syed M; Cohen, Jonathan; McLaughlin, Matthew; Dalal, Hema R

    2008-01-01

    Zosyn® , also known as Tazocin® for injection, contains piperacillin and tazobactam and was approved by the US Food and Drug Administration in 1993 for the treatment of indicated serious infections. In 1995, United States Pharmacopoeia and European Pharmacopoeias reduced the particulate limit for injectables by 40%, based on general safety concerns. Wyeth attempted to control sporadic batch failures (associated with increased particulate formation) by shortening product expiration dating from 36 to 24 months and optimizing the stopper siliconization process. These modifications did not correct the problem completely. Wyeth reformulated Zosyn by incorporating two stabilizing functional excipients, ethylene diamine tetraacetic acid disodium salt (EDTA disodium) and sodium citrate, which solved the particulate formation problem. These two functional excipients also allowed for the first time Y-site coadministration of reformulated Zosyn product with amikacin and gentamicin at specific doses and concentrations, and with certain diluents, and the use of Ca++ ion-containing Lactated Ringer’s for admixture preparation. Reformulated Zosyn (approved 2005) may provide useful options of drug administration to healthcare professionals to lessen levels of particulates. Supportive data is provided for the expanded compatibility of reformulated Zosyn with different types of Ringer’s solutions used globally and for the Y-site coadministration of amikacin and gentamicin aminoglycosides. PMID:18728835

  12. Antiallergic activity of ginseng and its ginsenosides.

    PubMed

    Choo, Min-Kyung; Park, Eun-Kyung; Han, Myung Joo; Kim, Dong-Hyun

    2003-06-01

    In this study, we measured the antiallergic activities of ginsenosides isolated from the root of Panax ginseng ( Araliaceae), and of their metabolites, as produced by human intestinal bacteria. Compound K, which was identified as a main metabolite, had the most potent inhibitory activity on beta-hexosaminidase release from RBL-2H3 cells and on the PCA reaction. The inhibitory activity of compound K was more potent than that of disodium cromoglycate, one of the commercial anti-allergic drugs. This compound demonstrated a membrane stabilizing action on differential scanning calorimetry. However, compound K did not inhibit the activation of hyaluronidase and did not scavenge active oxygen. These results suggest that the antiallergic action of compound K originates from its cell membrane stabilizing activity and that the ginsenosides of ginseng are prodrugs with extensive antiallergic properties. Abbreviations. compound K:20- O-beta- D-glucopyranosyl-20( S)-protopanaxadiol DNP:dinitrophenol DSCG:disodium cromoglycate DPPC:dipalmitoylphosphatidylcholine DPPH:1,1-diphenyl-2-picrylhydrazyl HSA:human serum albumin IC 50 :50% inhibitory concentration EC 50 :50% effective concentration XOD:xanthine oxidase ICR:Institute of Cancer Research PBS:phosphate buffered saline PCA:passive cutaneous anaphylaxis RAW264.7:mouse monocyte leukemiaRBL-2H3: rat basophil leukemia SD:Sprague-Dawley PMID:12865969

  13. TLC--densitometric method for qualitative analysis of betamethasone and its related compounds in pharmacautical preparations.

    PubMed

    Dolowy, Małgorzata; Pyka, Alina

    2014-01-01

    A new simple and rapid TLC-densitometric procedure for the separation and identification of betamethasone and its related substances, betamethasone-17,21-dipropionate, betamethasone-17-valerate, betamethasone-21-valerate and also betamethasone disodium phosphate was developed. One of the chromatographic systems proposed in this study, which has been satisfactory applied in separation of four pairs of examined compounds was silica gel 60F254 (E. Merck, Art. 1.05554) and a mixture containing chloroform-methanol-acetic acid (99.5%) in volume composition 28:5:0.5. Densitometric measurements were done using densitometer TLC Scanner 3 at 246 nm. The proposed method was checked in terms of its specificity for the determination of betamethasone-17,21-dipropionate and betamethasone disodium phosphate in commercially available products containing both compounds, separately, as active ingredients. The results showed that the method is suitable for qualitative analysis of betamethasone derivatives in simple and combined pharmaceuticals in various dosage forms e.g., lotion and injection solution. It also can be applied in quality control of pharmaceutical formulations of betamethasone and its related compounds in form of salts and esters. PMID:25745764

  14. Synthesis of phosphatidylcholine under possible primitive earth conditions

    NASA Technical Reports Server (NTRS)

    Rao, M.; Eichberg, J.; Oro, J.

    1982-01-01

    Using a primitive earth evaporating pond model, the synthesis of phosphatidylcholine was accomplished when a reaction mixture of choline chloride and disodium phosphatidate, in the presence of cyanamide and traces of acid, was evaporated and heated at temperatures ranging from 25 to 100 C for 7 hours. Optimum yields of about 15% were obtained at 80 C. Phosphatidylcholine was identified by chromatographic, chemical and enzymatic degradation methods. On enzymatic hydrolysis with phospholipase A2 and phospholipase C, lysophosphatidylcholine and phosphorylcholine were formed, respectively. Alkaline hydrolysis gave glycerophosphorylcholine. The synthesis of phosphatidylcholine as the major compound was accompanied by the formation of lysophosphatidylcholine in smaller amounts. Cyanamide was found to be essential for the formation of phosphatidylcholine, and only traces of HCl, of the order of that required to convert the disodium phosphatidate to free phosphatidic acid were found necessary for the synthesis. This work suggests that phosphatidylcholine, which is an essential component of most biological membranes, could have been synthesized on the primitive earth.

  15. Surfactants, Aromatic and Isoprenoid Compounds, and Fatty Acid Biosynthesis Inhibitors Suppress Staphylococcus aureus Production of Toxic Shock Syndrome Toxin 1▿

    PubMed Central

    McNamara, Peter J.; Syverson, Rae Ellen; Milligan-Myhre, Kathy; Frolova, Olga; Schroeder, Sarah; Kidder, Joshua; Hoang, Thanh; Proctor, Richard A.

    2009-01-01

    Menstrual toxic shock syndrome is a rare but potentially life-threatening illness manifest through the actions of Staphylococcus aureus toxic shock syndrome toxin 1 (TSST-1). Previous studies have shown that tampon additives can influence staphylococcal TSST-1 production. We report here on the TSST-1-suppressing activity of 34 compounds that are commonly used additives in the pharmaceutical, food, and perfume industries. Many of the tested chemicals had a minimal impact on the growth of S. aureus and yet were potent inhibitors of TSST-1 production. The TSST-1-reducing compounds included surfactants with an ether, amide, or amine linkage to their fatty acid moiety (e.g., myreth-3-myristate, Laureth-3, disodium lauroamphodiacetate, disodium lauramido monoethanolamido, sodium lauriminodipropionic acid, and triethanolamine laureth sulfate); aromatic compounds (e.g. phenylethyl and benzyl alcohols); and several isoprenoids and related compounds (e.g., terpineol and menthol). The membrane-targeting and -altering effects of the TSST-1-suppressing compounds led us to assess the activity of molecules that are known to inhibit fatty acid biosynthesis (e.g., cerulenin, triclosan, and hexachlorophene). These compounds also reduced S. aureus TSST-1 production. This study suggests that more additives than previously recognized inhibit the production of TSST-1. PMID:19223628

  16. Economic evaluation of first-line and maintenance treatments for advanced non-small cell lung cancer: a systematic review

    PubMed Central

    Chouaïd, Christos; Crequit, Perinne; Borget, Isabelle; Vergnenegre, Alain

    2015-01-01

    During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC), with a growing financial effect on patients and society. The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments. We reviewed economic analyses of NSCLC therapies published between 2004 and 2014. In first-line settings, in unselected patients with advanced NSCLC, the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets. In patients with nonsquamous NSCLC, the incremental cost-effectiveness ratios (ICERs) per life-year gained (LYG) were $83,537, $178,613, and more than $300,000 for cisplatin-pemetrexed compared with, respectively, cisplatin-gemcitabine, cisplatin-carboplatin-paclitaxel, and carboplatin-paclitaxel-bevacizumab. For all primary chemotherapy agents, use of carboplatin is associated with slightly higher costs than cisplatin. In all the analysis, bevacizumab had an ICER greater than $150,000 per quality-adjusted life-year (QALY). In epidermal growth factor receptor mutated advanced NSCLC, compared with carboplatin-paclitaxel doublet, targeted therapy based on testing available tissue yielded an ICER of $110,644 per QALY, and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Compared with the triplet carboplatin-paclitaxel-bevacizumab, testing and rebiopsy strategies had ICERs of $25,547 and $44,036 per QALY, respectively. In an indirect comparison, ICERs per LYG and QALY of erlotinib versus gefitinib were $39,431 and $62,419, respectively. In anaplastic lymphoma kinase-positive nonsquamous advanced NSCLC, the ICER of first-line crizotinib compared with that of chemotherapy was $255,970 per QALY. For maintenance therapy, gefitinib had an ICER of $19,214 per QALY, erlotinib had an ICER of $127,343 per LYG, and pemetrexed had an ICER varying between $183,589 and $205,597 per LYG. Most recent NSCLC strategies are based on apparently no cost

  17. Factors associated with survival in a large series of patients with malignant pleural mesothelioma in New South Wales

    PubMed Central

    Linton, A; Pavlakis, N; O'Connell, R; Soeberg, M; Kao, S; Clarke, S; Vardy, J; van Zandwijk, N

    2014-01-01

    Background: Although the prognosis of most patients presenting with malignant pleural mesothelioma (MPM) is poor, a small proportion survives long term. We investigated factors associated with survival in a large patient series. Methods: All patients registered with the NSW Dust Diseases Board (2002–2009) were included in an analysis of prognostic factors using Kaplan–Meier and Cox regression analysis. On the basis of these analyses, we developed a risk score (Prognostic Index (PI)). Results: We identified 910 patients: 90% male; histology (epithelioid 60% biphasic 13% sarcomatoid 17%); stage (Tx-I-II 48% III-IV 52%); and calretinin expression (91%). Treatment: chemotherapy(CT) 44%, and extrapleural-pneumonectomy (EPP) 6%. Median overall survival (OS) was 10.0 months. Longer OS was associated with: age <70 (13.5 vs 8.5 months; P<0.001); female gender (12.0 vs 9.9 months; P<0.001); epithelioid subtype (13.3 vs 6.2 months; P<0.001); ECOG status 0 (27.4 vs 9.7 months; P=0.015), calretinin expression (10.9 vs 5.5 months; P<0.001); neutrophil–lymphocyte ratio (NLR) <5 (11.9 vs 7.5 months; P<0.001); platelet count <400 (11.5 vs 7.2 months; P<0.001); and normal haemoglobin (16.4 vs 8.8 months; P<0.001). On time-dependent analysis, patients receiving pemetrexed-based chemotherapy (HR=0.83; P=0.048) or EPP (HR=0.41; P<0.001) had improved survival. Age, gender, histology, calretinin and haematological factors remained significant on multivariate analysis. In all, 24% of patients survived >20 months: 16% of these receiving EPP, and 66% CT. The PI offered improved prognostic discrimination over one of the existing prognostic models (EORTC). Conclusions: We identified calretinin expression, age, gender, histological subtype, platelet count and haemoglobin level as independent prognostic factors. Patients undergoing EPP or pemetrexed-based chemotherapy demonstrated better survival, but 84% and 34% of long survivors, respectively, did not receive radical surgery or

  18. Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma

    SciTech Connect

    Allen, Aaron M. . E-mail: aallen@lroc.harvard.edu; Czerminska, Maria; Jaenne, Pasi A.; Sugarbaker, David J.; Bueno, Raphael; Harris, Jay R.; Court, Laurence; Baldini, Elizabeth H.

    2006-07-01

    Purpose: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women's Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy. Methods and Materials: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m{sup 2}). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patients received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test. Results: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 5-57 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.3-22.3%), 15.2 Gy (range, 13.3-17 Gy), and 98.6% (range, 81-100%), respectively, as compared with 10.9% (range, 5.5-24.7%) (p = 0.08), 12.9 Gy (range, 8.7-16.9 Gy) (p = 0.07), and 90% (range

  19. Design, synthesis and biological evaluation of 6-substituted pyrrolo[2,3-d]pyrimidines as dual inhibitors of TS and AICARFTase and as potential antitumor agents.

    PubMed

    Liu, Yi; Li, Meng; Zhang, Hongying; Yuan, Jiangsong; Zhang, Congying; Zhang, Kai; Guo, Huicai; Zhao, Lijuan; Du, Yumin; Wang, Lei; Ren, Leiming

    2016-06-10

    A new series of 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidines, with an isosteric replacement of the side chain amide moiety to a sulfur atom, were designed and synthesized as multitargeted antifolates as well as potential antitumor agents. Starting from previously synthesized 2-amino-4-oxo-pyrrolo[2,3-d]pyrimidin-6-yl-acetic acid, a reduction by lithium triethylborohydride and successive mesylation afforded the key mesylate. Nucleophilic substitution by mercaptoacetic or mercaptopropionic acid methyl esters, followed by hydrolysis and condensation with pyridinyl-methylamines provided the nonclassical compounds 1-6, whereas condensation with glutamic acid diethyl ester hydrochloride and saponification afforded the classical analogs 7-8. All target compounds exhibited inhibitory activities toward KB, SW620 and A549 tumor cell lines. The most potent compounds of this series, 7 and 8, are better inhibitors against A549 cells than methotrexate (MTX) and pemetrexed (PMX). Nucleoside protection assays establish compound 8 a dual inhibitor of thymidylate synthase (TS) and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFTase) targeting both de novo thymidylate and purine nucleotide biosynthesis, which is further verified by the molecular modeling studies. Analogous to PMX, target compound 8 alternates the cell cycle of SW620 cells with S-phase accumulation and induces apoptosis, leading to cell death. PMID:27017552

  20. Triptolide and its prodrug minnelide suppress Hsp70 and inhibit in vivo growth in a xenograft model of mesothelioma.

    PubMed

    Jacobson, Blake A; Chen, Esther Z; Tang, Shaogeng; Belgum, Holly Sedgwick; McCauley, Joel A; Evenson, Kristen A; Etchison, Ryan G; Jay-Dixon, Joe; Patel, Manish R; Raza, Ahmad; Saluja, Ashok K; D'Cunha, Jonathan; Kratzke, Robert A

    2015-03-01

    Malignant mesothelioma is a devastating disease with a poor prognosis for which there is a clear need for more successful therapeutic approaches. Triptolide, a diterpenoid triepoxide, is a highly effective agent against several cancer types in animal models. Owing to triptolide's poor solubility in water, a water-soluble analog, minnelide, was synthesized. Minnelide is a prodrug of triptolide and is activated by exposure to phosphatases that are found in all body tissues, including blood. Mesothelioma cells were treated in vitro with minnelide or its parent compound, triptolide. Minnelide and triptolide were both found to significantly reduce mesothelioma cell viability and induce apoptosis. The level of Hsp70, a protein that promotes cancer cell survival, was measured in mesothelioma cells before and after treatment with triptolide. Hsp70 levels were decreased in a dose-dependent manner. In addition, triptolide sensitized cells to gemcitabine and pemetrexed as measured by cell viability. Mice bearing mesothelioma flank tumors were treated with daily injections (28 d) of minnelide or saline solution and xenograft tumor growth recorded. Mice displayed significantly reduced tumor burden. These findings support the clinical evaluation of minnelide therapy for mesothelioma. PMID:26000097