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Sample records for 89b comparing adjuvant

  1. Mixed adjuvant formulations reveal a new combination that elicit antibody response comparable to Freund's adjuvants.

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    Rachel P J Lai

    Full Text Available Adjuvant formulations capable of inducing high titer and high affinity antibody responses would provide a major advance in the development of vaccines to viral infections such as HIV-1. Although oil-in-water emulsions, such as Freund's adjuvant (FCA/FIA, are known to be potent, their toxicity and reactogenicity make them unacceptable for human use. Here, we explored different adjuvants and compared their ability to elicit antibody responses to FCA/FIA. Recombinant soluble trimeric HIV-1 gp140 antigen was formulated in different adjuvants, including FCA/FIA, Carbopol-971P, Carbopol-974P and the licensed adjuvant MF59, or combinations of MF59 and Carbopol. The antigen-adjuvant formulation was administered in a prime-boost regimen into rabbits, and elicitation of antigen binding and neutralizing antibodies (nAbs was evaluated. When used individually, only FCA/FIA elicited significantly higher titer of nAbs than the control group (gp140 in PBS (p<0.05. Sequential prime-boost immunizations with different adjuvants did not offer improvements over the use of FCA/FIA or MF59. Remarkably however, the concurrent use of the combination of Carbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA (p<0.05. This combination was not associated with any obvious local or systemic adverse effects. Antibody competition indicated that the majority of the neutralizing activities were directed to the CD4 binding site (CD4bs. Increased antibody titers to the gp41 membrane proximal external region (MPER and gp120 V3 were detected when the more potent adjuvants were used. These data reveal that the combination of Carbopol-971P and MF59 is unusually potent for eliciting nAbs to a variety of HIV-1 nAb epitopes.

  2. A randomised controlled trial comparing the effect of adjuvant ...

    African Journals Online (AJOL)

    between adjuvant intrathecal 2 mg midazolam as compared to intrathecal 20 micrograms fentanyl for patients undergoing ... in mental processes, respiratory depression, and other .... nificance level and power of 90%, the required sample.

  3. Adjuvant chemotherapy in early breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent

    2016-01-01

    % of patients aged 40 or younger in 77B had regular menses throughout chemotherapy, the corresponding percentage was 37 in 82B and 47 in 89B. The DBCG in collaboration with a Swedish and a Dutch centre participating in the DBCG trial 89B compared CMF with ovarian ablation in premenopausal high-risk breast...... are not clinically useful by themselves as other chemotherapy regimens have been more efficacious, and knowledge is still lacking regarding the benefits from adding ovarian suppression to chemotherapy plus tamoxifen. The results from the DBCG 77B and 82C are in accordance with other large adjuvant trials...... adjuvant trials demonstrated that patients with either TOP2A or centromere 17 aberrations, but not with HER2 amplification, benefit from anthracycline-containing adjuvant chemotherapy. Anthracyclins have additional distinct biological mechanisms; and results from the DBCG 89D suggested that tumours...

  4. The Effect of Neoadjuvant Chemotherapy Compared to Adjuvant Chemotherapy in Healing after Nipple-Sparing Mastectomy.

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    Frey, Jordan D; Choi, Mihye; Karp, Nolan S

    2017-01-01

    Nipple-sparing mastectomy is the latest advancement in the treatment of breast cancer. The authors aimed to investigate the effects of neoadjuvant and adjuvant chemotherapy in nipple-sparing mastectomy. Patients undergoing nipple-sparing mastectomy from 2006 to June of 2015 were identified. Results were stratified by presence of neoadjuvant or adjuvant chemotherapy. A total of 840 nipple-sparing mastectomies were performed. Twenty-eight were in those who received neoadjuvant chemotherapy and 93 were in patients receiving adjuvant chemotherapy. Patients receiving both neoadjuvant and adjuvant chemotherapy were included in the neoadjuvant group. Nipple-sparing mastectomies that received neoadjuvant (with or without adjuvant) chemotherapy were compared to those in patients who received adjuvant chemotherapy. Those with neoadjuvant (with or without adjuvant) chemotherapy were more likely to have explantation (p = 0.0239) and complete nipple-areola complex necrosis (p = 0.0021). Those with neoadjuvant (with or without adjuvant) chemotherapy were more likely to have implant explantation (p = 0.0015) and complete nipple-areola complex necrosis (p = 0.0004) compared to those with no chemotherapy. Compared to nipple-sparing mastectomies in patients with no chemotherapy, those with adjuvant chemotherapy were more likely to have a hematoma (p = 0.0021). Those that received both neoadjuvant and adjuvant chemotherapy were more likely to have complete nipple-areola complex necrosis compared with both the neoadjuvant chemotherapy-only and adjuvant chemotherapy-only groups (p < 0.0001). Nipple-sparing mastectomy is safe to perform in the setting of neoadjuvant and adjuvant chemotherapy. As a whole, neoadjuvant (with or without adjuvant) chemotherapy increases risk of complications. Therapeutic, III.

  5. Comparable quality attributes of hepatitis E vaccine antigen with and without adjuvant adsorption-dissolution treatment.

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    Zhang, Yue; Li, Min; Yang, Fan; Li, Yufang; Zheng, Zizheng; Zhang, Xiao; Lin, Qingshan; Wang, Ying; Li, Shaowei; Xia, Ningshao; Zhang, Jun; Zhao, Qinjian

    2015-01-01

    Most vaccines require adjuvants for antigen stabilization and immune potentiation. Aluminum-based adjuvants are the most widely used adjuvants for human vaccines. Previous reports demonstrated the preservation of antigen conformation and other antigen characteristics after recovery from adjuvanted Hepatitis B and human papillomavirus vaccines. In this study, we used a combination of various physiochemical and immunochemical methods to analyze hepatitis E vaccine antigen quality attributes after recovery from adjuvants. All biochemical and biophysical methods showed similar characteristics of the p239 protein after recovery from adjuvanted vaccine formulation compared to the antigen in solution which never experienced adsorption/desorption process. Most importantly, we demonstrated full preservation of key antigen epitopes post-recovery from adjuvanted vaccine using a panel of murine monoclonal antibodies as exquisite probes. Antigenicity of p239 was probed with a panel of 9 mAbs using competition/blocking ELISA, surface plasmon resonance and sandwich ELISA methods. These multifaceted analyses demonstrated the preservation of antigen key epitopes and comparable protein thermal stability when adsorbed on adjuvants or of the recovered antigen post-dissolution treatment. A better understanding of the antigen conformation in adjuvanted vaccine will enhanced our knowledge of antigen-adjuvant interactions and facilitate an improved process control and development of stable vaccine formulation.

  6. Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants.

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    Olafsdottir, Thorunn A; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H E; Reed, Steven G; Harandi, Ali M

    2016-12-13

    A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

  7. Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

    Science.gov (United States)

    Olafsdottir, Thorunn A.; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H. E.; Reed, Steven G.; Harandi, Ali M.

    2016-12-01

    A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

  8. The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial.

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    Skinner, D G; Daniels, J R; Russell, C A; Lieskovsky, G; Boyd, S D; Nichols, P; Kern, W; Sakamoto, J; Krailo, M; Groshen, S

    1991-03-01

    We assigned 91 patients with deeply invasive, pathological stage P3, P4 or N+ and Mo transitional cell carcinoma of the bladder (with or without squamous or glandular differentiation) to adjuvant chemotherapy or to observation after radical cystectomy and pelvic lymph node dissection. For most patients chemotherapy was planned as 4 courses at 28-day intervals of 100 mg./M.2 cisplatin, 60 mg./M.2 doxorubicin and 600 mg./M.2 cyclophosphamide. A significant delay was shown in the time to progression (p = 0.0010) with 70% of the patients assigned to chemotherapy free of disease at 3 years compared to 46% in the observation group. Median survival time for patients in the chemotherapy group was 4.3 years compared to 2.4 years in the observation group (p = 0.0062). In addition to treatment groups, important prognostic factors included age, gender and lymph node status. The number of involved lymph nodes was the single most important variable. We recommend adjuvant chemotherapy for patients with invasive transitional cell carcinoma after definitive surgical resection.

  9. Humoral and cellular immunity to hepatitis B virus-derived antigens: comparative activity of Freund complete adjuvant alum, and liposomes.

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    Sanchez, Y; Ionescu-Matiu, I; Dreesman, G R; Kramp, W; Six, H R; Hollinger, F B; Melnick, J L

    1980-01-01

    Complete Freud adjuvant, aluminum gel, and liposomes were compared for their ability to enhance the immunogenicity of an intact 22-nm HBsAg particle vaccine and an HBsAg-derived polypeptide vaccine in guinea pigs. Both humoral and cell-mediated immune responses were evaluated. The greatest immune response was obtained with complete Freund adjuvant, regardless of the antigen preparation. Aluminum gel appeared to be a better adjuvant for 22-nm HBsAg particles, but the liposomes rendered polypeptide preparations more immunogenic. The possibility that various proportions were entrapped in aqueous compartments instead of being inserted into the lipid bilayers of liposomes might account for this difference. The development of both humoral and cellular immunity was dependent upon the use of an adjuvant, because aqueous preparations had poor immunogenicity. PMID:7014445

  10. A Comparative study of intrathecal dexmedetomidine and fentanyl as adjuvants to Bupivacaine

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    Rajni Gupta

    2011-01-01

    Full Text Available Background: Various adjuvants have been used with local anesthetics in spinal anesthesia to avoid intraoperative visceral and somatic pain and to provide prolonged postoperative analgesia. Dexmedetomidine, the new highly selective α2-agonist drug, is now being used as a neuraxial adjuvant. The aim of this study was to evaluate the onset and duration of sensory and motor block, hemodynamic effect, postoperative analgesia, and adverse effects of dexmedetomidine or fentanyl given intrathecally with hyperbaric 0.5% bupivacaine. Materials and Methods: Sixty patients classified in American Society of Anesthesiologists classes I and II scheduled for lower abdominal surgeries were studied. Patients were randomly allocated to receive either 12.5 mg hyperbaric bupivacaine plus 5 μg dexmedetomidine (group D, n=30 or 12.5 mg hyperbaric bupivacaine plus 25 μg fentanyl (group F, n=30 intrathecal. Results: Patients in dexmedetomidine group (D had a significantly longer sensory and motor block time than patients in fentanyl group (F. The mean time of sensory regression to S1 was 476±23 min in group D and 187±12 min in group F (P<0.001. The regression time of motor block to reach modified Bromage 0 was 421±21 min in group D and 149±18 min in group F (P<0.001. Conclusions: Intrathecal dexmedetomidine is associated with prolonged motor and sensory block, hemodynamic stability, and reduced demand for rescue analgesics in 24 h as compared to fentanyl.

  11. Cerebral biochemical pathways in experimental autoimmune encephalomyelitis and adjuvant arthritis: a comparative metabolomic study.

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    Norbert W Lutz

    Full Text Available Many diseases, including brain disorders, are associated with perturbations of tissue metabolism. However, an often overlooked issue is the impact that inflammations outside the brain may have on brain metabolism. Our main goal was to study similarities and differences between brain metabolite profiles of animals suffering from experimental autoimmune encephalomyelitis (EAE and adjuvant arthritis (AA in Lewis rat models. Our principal objective was the determination of molecular protagonists involved in the metabolism underlying these diseases. EAE was induced by intraplantar injection of complete Freund's adjuvant (CFA and spinal-cord homogenate (SC-H, whereas AA was induced by CFA only. Naive rats served as controls (n = 9 for each group. Two weeks after inoculation, animals were sacrificed, and brains were removed and processed for metabolomic analysis by NMR spectroscopy or for immunohistochemistry. Interestingly, both inflammatory diseases caused similar, though not identical, changes in metabolites involved in regulation of brain cell size and membrane production: among the osmolytes, taurine and the neuronal marker, N-acetylaspartate, were decreased, and the astrocyte marker, myo-inositol, slightly increased in both inoculated groups compared with controls. Also ethanolamine-containing phospholipids, sources of inflammatory agents, and several glycolytic metabolites were increased in both inoculated groups. By contrast, the amino acids, aspartate and isoleucine, were less concentrated in CFA/SC-H and control vs. CFA rats. Our results suggest that inflammatory brain metabolite profiles may indicate the existence of either cerebral (EAE or extra-cerebral (AA inflammation. These inflammatory processes may act through distinct pathways that converge toward similar brain metabolic profiles. Our findings open new avenues for future studies aimed at demonstrating whether brain metabolic effects provoked by AA are pain/stress-mediated and

  12. A COMPARATIVE EVALUATION OF CLONIDINE & DEXMEDETOMIDINE AS ADJUVANTS TO ROPIVACAINE IN CAUDAL BLOCK IN CHILDREN

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    Jyoti

    2015-07-01

    Full Text Available BACKGROUND: Caudal analgesia has been successfully used in paediatric patients since 1933. Ropivacaine a stereo isomer of Bupivacaine was used to increase duration of analgesia. The present study is designed to compare clonidine and dexmedetomidine as adjuvants to Ropivacaine in caudal block in children. METHODS: A total of 60 patients of 3 - 10 years age, either sex, ASA I/II posted for infraumblical surgeries under GA with caudal analgesia were randomly allocated to receive 0.2% ropivacaine plain@1ml/kg+normal saline (1ml, 0.2% ropivacaine @1ml/kg+clonidine 1microg/kg (1ml, 0.2% ropivacaine @1ml/kg+dexmedetomidine 1microg/kg(1ml. The children were monitored postoperatively for duration of analgesia, sedation score and postoperative complications if any. RESULTS: Duration of analgesia was maximum in Group - III (Ropivacaine+ Dexmedetomidine – 14hrs., 12hrs. I n Group - II (Ropivacaine+Clonidine and 6 - 8 hrs. I n Group - I (Ropivacaine Plain. Children were more sedated in early postoperative period in Group - II & III as compared to Group - I. CONCLUSION : Duration of analgesia was prolonged in Group - II & III, the same group children were more sedated and calm in postoperative period.

  13. Adjuvant radiotherapy for endometrial cancer--a comparative review of radiotherapy technique with acute toxicity.

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    Koh, Y V; Tang, J I; Choo, B A; Koh, M S; Lee, K M

    2014-01-01

    The addition of pelvic radiotherapy to brachytherapy (EBRT-BT) in early-stage endometrial cancer is controversial and may cause unnecessary toxicity. The incidence of acute toxicity of EBRT-BT will have an impact on clinical decision and patient compliance but is currently poorly understood. This study compares the acute toxicities of EBRT-BT versus BT alone. Seventy-nine patients with FIGO Stage IA-II endometrial cancer who underwent adjuvant radiotherapy, (EBRT-BT or BT alone) from 2001 to 2011 were included in the study. Medical records of these patients were reviewed retrospectively and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients were followed up for at least three months post-treatment to assess resolution of toxicity. The mean age of the study group was 60.6 years. Median follow-up was four years. Forty patients received EBRT-BT. There was a 37% increase in Grade 1-3 diarrhea with the addition of pelvic radiotherapy (OR 18.67, p < 0.0005) and a 34% increase in lethargy (p < 0.0005). There was also an increased occurrence of genitourinary and skin toxicities. Two patients in the EBRT-BT group required hospitalisation for severe diarrhea and three patients were unable to complete the treatment. All acute toxicities had resolved by three months post treatment. EBRT-BT causes significantly more acute toxicities compared to BT alone. Patients should be informed of this during counselling.

  14. Influence of adjuvant detached mindfulness and stress management training compared to pharmacologic treatment in primiparae with postpartum depression.

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    Ahmadpanah, Mohammad; Nazaribadie, Marzieh; Aghaei, Elham; Ghaleiha, Ali; Bakhtiari, Azade; Haghighi, Mohammad; Bahmani, Dena Sadeghi; Akhondi, Amineh; Bajoghli, Hafez; Jahangard, Leila; Holsboer-Trachsler, Edith; Brand, Serge

    2017-07-18

    Ten to 15% of mothers experience postpartum depression (PPD). If untreated, PPD may negatively affect mothers' and infants' mental health in the long term. Accordingly, effective treatments are required. In the present study, we investigated the effect of detached mindfulness (DM) and stress management training (SMT) as adjuvants, compared to pharmacologic treatment only, on symptoms of depression in women with PPD. Forty-five primiparae (mean age: M = 24.5 years) with diagnosed PPD and treated with an SSRI (citalopram; CIT) took part in the study. At baseline, they completed questionnaires covering socio-demographic data and symptoms of depression. Experts rated also symptoms of depression. Next, participants were randomly assigned to one of the following study conditions: adjuvant detached mindfulness (CIT+DM); adjuvant stress management training (CIT+SMT); control condition (CIT). Self- and experts' ratings were completed at the end of the study 8 weeks later, and again at 8 weeks follow-up. Symptoms of depression decreased significantly over time, but more so in the CIT+DM and CIT+SMT group, compared to the control condition. The pattern of results remained stable at follow-up. In primiparae with PPD and treated with a standard SSRI, adjuvant psychotherapeutic interventions led to significant and longer-lasting improvements.

  15. Comparative assessment of humoral immune responses of aluminum hydroxide and oil-emulsion adjuvants in Influenza (H9N2) and Newcastle inactive vaccines to chickens.

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    Jafari, Mahdie; Moghaddam Pour, Masoud; Taghizadeh, Morteza; Masoudi, Shahin; Bayat, Zahra

    2017-02-01

    Context Adjuvants are compounds used in the preparation of inactive vaccines to enhance the immune response. Aluminum hydroxide (alum) is one of the first compounds approved by the Food and Drug Administration, which is used as adjuvants in vaccine products for humans. Montanide ISA 70 is an oil-emulsion adjuvant and is used in poultry inactive vaccines. Objective In this study, the effects of alum adjuvant on the efficiency and induction of immune response in inactive vaccines of Influenza and Newcastle are compared with those of ISA 70. Materials and methods Six groups of 7-d-old specific-pathogen-free chickens were inoculated with 0.3 ml of the prepared vaccines via the subcutaneous route in the neck. Immune response in each group after 7, 14, 21, 31, 41, and 45 d was evaluated using the technique of hemagglutination inhibition. Results The results were compared using SPSS software. Results showed that vaccines containing adjuvant ISA 70 depicted a higher increase in the immune response and adjuvant of 20% alum is similar to adjuvant of ISA 70 in boosting the immune system. There was no statistically significant difference between 10% and 20% alum, but these adjuvants are visibly different from ISA 70. Conclusion In conclusion, alum can be used as an easily accessible, harmless, and effective adjuvant; however, to increase the immune period using the inactive vaccines for poultry, more research would be necessary.

  16. Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study.

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    Van Damme, Pierre; Arnou, Robert; Kafeja, Froukje; Fiquet, Anne; Richard, Patrick; Thomas, Stéphane; Meghlaoui, Gilles; Samson, Sandrine Isabelle; Ledesma, Emilio

    2010-05-26

    Although seasonal influenza vaccine is effective in the elderly, immune responses to vaccination are lower in the elderly than in younger adults. Strategies to optimise responses to vaccination in the elderly include using an adjuvanted vaccine or using an intradermal vaccination route. The immunogenicity of an intradermal seasonal influenza vaccine was compared with that of an adjuvanted vaccine in the elderly. Elderly volunteers (age > or = 65 years) were randomised to receive a single dose of trivalent seasonal influenza vaccine: either a split-virion vaccine containing 15 microg haemagglutinin [HA]/strain/0.1-ml dose administered intradermally, or a subunit vaccine (15 microg HA/strain/0.5-ml dose) adjuvanted with MF59C.1 and administered intramuscularly. Blood samples were taken before and 21 +/- 3 days post-vaccination. Anti-HA antibody titres were assessed using haemagglutination inhibition (HI) and single radial haemolysis (SRH) methods. We aimed to show that the intradermal vaccine was non-inferior to the adjuvanted vaccine. A total of 795 participants were enrolled (intradermal vaccine n = 398; adjuvanted vaccine n = 397). Non-inferiority of the intradermal vaccine was demonstrated for the A/H1N1 and B strains, but not for the A/H3N2 strain (upper bound of the 95% CI = 1.53) using the HI method, and for all three strains by the SRH method. A post-hoc analysis of covariance to adjust for baseline antibody titres demonstrated the non-inferiority of the intradermal vaccine by HI and SRH methods for all three strains. Both vaccines were, in general, well tolerated; the incidence of injection-site reactions was higher for the intradermal (70.1%) than the adjuvanted vaccine (33.8%) but these reactions were mild and of short duration. The immunogenicity and safety of the intradermal seasonal influenza vaccine in the elderly was comparable with that of the adjuvanted vaccine. Intradermal vaccination to target the immune properties of the skin appears to be an

  17. Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study

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    Thomas Stéphane

    2010-05-01

    Full Text Available Abstract Background Although seasonal influenza vaccine is effective in the elderly, immune responses to vaccination are lower in the elderly than in younger adults. Strategies to optimise responses to vaccination in the elderly include using an adjuvanted vaccine or using an intradermal vaccination route. The immunogenicity of an intradermal seasonal influenza vaccine was compared with that of an adjuvanted vaccine in the elderly. Methods Elderly volunteers (age ≥ 65 years were randomised to receive a single dose of trivalent seasonal influenza vaccine: either a split-virion vaccine containing 15 μg haemagglutinin [HA]/strain/0.1-ml dose administered intradermally, or a subunit vaccine (15 μg HA/strain/0.5-ml dose adjuvanted with MF59C.1 and administered intramuscularly. Blood samples were taken before and 21 ± 3 days post-vaccination. Anti-HA antibody titres were assessed using haemagglutination inhibition (HI and single radial haemolysis (SRH methods. We aimed to show that the intradermal vaccine was non-inferior to the adjuvanted vaccine. Results A total of 795 participants were enrolled (intradermal vaccine n = 398; adjuvanted vaccine n = 397. Non-inferiority of the intradermal vaccine was demonstrated for the A/H1N1 and B strains, but not for the A/H3N2 strain (upper bound of the 95% CI = 1.53 using the HI method, and for all three strains by the SRH method. A post-hoc analysis of covariance to adjust for baseline antibody titres demonstrated the non-inferiority of the intradermal vaccine by HI and SRH methods for all three strains. Both vaccines were, in general, well tolerated; the incidence of injection-site reactions was higher for the intradermal (70.1% than the adjuvanted vaccine (33.8% but these reactions were mild and of short duration. Conclusions The immunogenicity and safety of the intradermal seasonal influenza vaccine in the elderly was comparable with that of the adjuvanted vaccine. Intradermal vaccination to target the

  18. A COMPARATIVE STUDY OF INTRATHECAL DEXMEDETOMIDINE AND FENTANYL AS ADJUVANTS TO BUPIVACAINE FOR INFRA - UMBILICAL SURGERIES

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    Ch. Srinivas

    2015-01-01

    Full Text Available BACKGROUND: Several adjuncts like adrenaline,opioids and alpha - 2 adrenergic agonists are being used with local anaesthetics intrathecally for prolongation of intra - operative and post - operative analgesia and to reduce the side - effects of high doses of local anaesthetics. [1] AIM: The present study was done to evaluate the onset and duration of sensory and motor block, hemodynamic effects, pos t - operative analgesia and adverse effects of Dexmedetomidine or Fentanyl given intrathecally with hyperbaric 0.5% Bupivacaine. MATERIALS AND METHODS: Ninety inpatients of ASA class I and II scheduled for various infra - umbilical surgeries under Sub - Arachnoi d Block were randomly divided into three groups of 30 each namely C (Control, D(Dexmedetomidine and F(Fentanyl. All received 12.5mg hyperbaric bupivacaine plus 0.5 ml Normal Saline in Group C (Control,5 μ g Dexmedetomidine (diluted in preservative free Normal saline of 0.5ml in Group D (Dexmedetomidine and 25 μ g Fentanyl (vol 0.5 ml in Group F (Fentanyl. The onset time to reach peak sensory and motor level, the regression time for sensory and motor block, hemodynamic changes and side - effects were not ed. RESULTS: The duration of sensory and motor block,rescue analgesia was significantly prolonged in Dexmedetomidine group when compared to that of the Fentanyl group which is longer than that of Control group. CONCLUSION: Dexmedetomidine 5 μg seems to be better than 25μg Fentanyl as a neuraxial adjuvant to hyperbaric Bupivacaine.

  19. A COMPARATIVE STUDY OF INTRATHECAL DEXMEDETOMIDINE AND FENTANYL AS ADJUVANTS TO BUPIVACAINE

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    Gollapalli Hanumanth

    2016-02-01

    Full Text Available INTRODUCTION Uncontrolled postoperative pain may produce a range of detrimental acute and chronic effects. Spinal anaesthesia provided by bupivacaine may be too short for providing postoperative analgesia. This study is conducted to evaluate the efficacy of intrathecal fentanyl and intrathecal dexmedetomidine as an adjuvant to hyperbaric bupivacaine with regards to the onset and duration of sensory and motor blockade, as well as postoperative analgesia and adverse effects. Hundred patients aged 18-55 years were randomly divided into two groups, each group consisting of 50 patients of either sex belonging to ASA class I and II posted for elective lower abdominal surgeries were given spinal anaesthesia using bupivacaine 0.5%, heavy 2.5 ml with either fentanyl 25µg (group F or 5µg of preservative free dexmedetomidine (group D. Assessment of the sensory and motor blockade were done at the end of each minute till the maximum level achieved. Measurement of blood pressure, pulse rate, respiratory rate and arterial oxygen saturation were obtained. Postoperatively the patients were observed for the duration of analgesia, time taken for complete regression of sensory blockade to S1 and time taken for complete recovery of motor power. RESULTS Our results showed a statistically highly significant prolongation of sensory and motor blockade, and postoperative analgesia in the dexmedetomidine group compared to the fentanyl group. In dexmedetomidine group four out of fifty patients, and in fentanyl group two out of fifty patients developed hypotension. In dexmedetomidine group five out of fifty patients, and in fentanyl group two out of fifty patients developed bradycardia. Incidence of pruritis is significantly high in fentanyl group.

  20. Three WASP-South Transiting Exoplanets: WASP-74b, WASP-83b, and WASP-89b

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    Hellier, Coel; Anderson, D. R.; Collier Cameron, A.; Delrez, L.; Gillon, M.; Jehin, E.; Lendl, M.; Maxted, P. F. L.; Pepe, F.; Pollacco, D.; Queloz, D.; Ségransan, D.; Smalley, B.; Smith, A. M. S.; Southworth, J.; Triaud, A. H. M. J.; Turner, O. D.; Udry, S.; West, R. G.

    2015-07-01

    We report the discovery of three new transiting hot Jupiters by WASP-South together with the TRAPPIST photometer and the Euler/CORALIE spectrograph. WASP-74b orbits a star of V = 9.7, making it one of the brighter systems accessible to southern telescopes. It is a 0.95MJup planet with a moderately bloated radius of 1.5 {R}{Jup} in a 2 day orbit around a slightly evolved F9 star. WASP-83b is a Saturn-mass planet at 0.3 {M}{Jup} with a radius of 1.0 {R}{Jup}. It is in a 5 day orbit around a fainter (V = 12.9) G8 star. WASP-89b is a 6 MJup planet in a 3 day orbit with an eccentricity of e = 0.2. It is thus similar to massive, eccentric planets such as XO-3b and HAT-P-2b, except that those planets orbit F stars whereas WASP-89 is a K star. The V = 13.1 host star is magnetically active, showing a rotation period of 20.2 days, while star spots are visible in the transits. There are indications that the planet’s orbit is aligned with the stellar spin. WASP-89 is a good target for an extensive study of transits of star spots.

  1. Three WASP-South transiting exoplanets: WASP-74b, WASP-83b & WASP-89b

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    Hellier, Coel; Cameron, A Collier; Delrez, L; Gillon, M; Jehin, E; Lendl, M; Maxted, P F L; Pepe, F; Pollacco, D; Queloz, D; Segransan, D; Smalley, B; Smith, A M S; Southworth, J; Triaud, A H M J; Turner, O D; Udry, S; West, R G

    2014-01-01

    We report the discovery of three new transiting hot Jupiters by WASP-South together with the TRAPPIST photometer and the Euler/CORALIE spectrograph. WASP-74b orbits a star of V = 9.7, making it one of the brighter systems accessible to Southern telescopes. It is a 0.95 M_Jup planet with a moderately bloated radius of 1.5 R_Jup in a 2-d orbit around a slightly evolved F9 star. WASP-83b is a Saturn-mass planet at 0.3 M_Jup with a radius of 1.0 R_Jup. It is in a 5-d orbit around a fainter (V = 12.9) G8 star. WASP-89b is a 6 M_Jup planet in a 3-d orbit with an eccentricity of e = 0.2. It is thus similar to massive, eccentric planets such as XO-3b and HAT-P-2b, except that those planets orbit F stars whereas WASP-89 is a K star. The V = 13.1 host star is magnetically active, showing a rotation period of 20.2 d, while star spots are visible in the transits. There are indications that the planet's orbit is aligned with the stellar spin. WASP-89 is a good target for an extensive study of transits of star spots.

  2. Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein) Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen.

    Science.gov (United States)

    Thim, Hanna L; Villoing, Stéphane; McLoughlin, Marian; Christie, Karen Elina; Grove, Søren; Frost, Petter; Jørgensen, Jorunn B

    2014-03-25

    Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag) formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions) can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV) as the test Ag, the combined use of two Toll-like receptor (TLR) ligand adjuvants, CpG oligonucleotides (ODNs) and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV) glycoprotein (G) was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs) before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing receptor (PRR

  3. Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen

    Directory of Open Access Journals (Sweden)

    Hanna L. Thim

    2014-03-01

    Full Text Available Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV as the test Ag, the combined use of two Toll-like receptor (TLR ligand adjuvants, CpG oligonucleotides (ODNs and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV glycoprotein (G was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing

  4. Comparative Study of Intrathecal Dexamethasone with Epinephrine as Adjuvants to Lidocaine in Cesarean Section

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    Fereshteh Naziri

    2013-09-01

    Full Text Available Background: Different additives have been used with local anesthetics to provide prolonged duration of sensory block in spinal anesthesia. The aim of present study was to evaluate the onset and duration of sensory block of intrathecal dexamethasone and epinephrine as adjuvants to lidocaine in patients who were candidate for cesarean section. Materials and Methods: This double-blind clinical trial research was conducted on 90 pregnant women candidate for cesarean section under spinal anesthesia. Patients were randomly allocated to receive intrathecally either 75 mg hyperbaric lidocaine plus 100 μg epinephrine or 75 mg hyperbaric lidocaine plus 4 mg dexamethasone or 75 mg hyperbaric lidocaine. The onset and duration of sensory block as well as postoperative analgesia were assessed. Results: The time to reach the peak sensory block in lidocaine group was shorter than that of other two groups (p<0.001. Duration of sensory block in the control group, dexamethasone group, and epinephrine group were 64.16±7.99 min, 74.79±12.78 min, and 99.30±10.93 min, respectively (p<0.001. Conclusion: The present research shows that intrathecal dexamethasone and intrathecal epinephrine as adjuvant to lidocaine increases sensory block duration in the women candidate for cesarean section.

  5. Comparing the Effect of Myristica fragrans and Flunixin on Adjuvant-Induced

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    Hossein Najafzadeh

    2014-02-01

    Full Text Available Background: Nutmeg, Myristica fragrans Houtt, has shown anti-inflammatory properties in some studies. At present experimental study, we evaluated the effect of seed extract of nutmeg on adjuvant-induced arthritis in rats in comparison with flunixin meglumine. Materials and Methods: Experimental study was done in six groups of Wistar rats (each group 8 rats as following: Group 1 was kept as control under similar conditions to other groups. All other rats received complete Freund's adjuvant at dose 0.1 ml which injected under skin of foot. Group 2 was received vehicle (normal saline. Group 3 received flunixin intraperitonealy at dose of 2 mg/kg body weight of rats daily for 12 days. Group4 to 6 received extract of nutmeg at dose 100, 200 and 300 mg/kg intraperitonealy and daily for 12 days. Four rats in each group were anesthetized and blood collected for serum analysis on 12th day. The ankle joint prepared for histopathological examination. The remained rats were kept until 21th day. Levels of the cytokine TNF-α in serum was measured using ELISA kit. Results: The serum levels of TNF-α in the group 2 were significantly increased; while nutmeg decreased the elevated TNF-α level in a dose-dependent manner but significantly with 300 mg/kg. The flunixin did not significantly decrease the levels of TNF-α. Nutmeg treated rats manifested pathological events in the ankle joints to a markedly lesser degree. Flunixin prevented pannus formation but it was ineffective in other lesions. Conclusion: Thus, nutmeg protected the joints against cartilage destruction and bone erosion in a dose-dependent manner.

  6. A COMPARATIVE STUDY ON HYPOTHALAMIC MECHANISMS OF ANALGESIA INDUCED BY FOUR KINDS OF ACUPUNCTURE THERAPIES IN ADJUVANT ARTHRITIS RATS

    Institute of Scientific and Technical Information of China (English)

    FU Yi; LIANG Fan-rong; TAO Qiao-lin

    2005-01-01

    Objective: To compare the mechanisms of analgesia induced by four kinds of acupuncture therapies at the hypothalamic level in adjuvant arthritic rats. Methods: Forty-eight SD rats were randomized into normal, model, electroacupuncture (EA), filiform needle (FN), pricking blood-letting (BL) and point injection (PI) groups, with 8 cases in each. EA (20-100 Hz, 2-4 V and duration of 20 min), FN, BL PI were respectively applied to "Kunlun" (昆仑BL 60). Arthritis model was established by injecting complete Freund's adjuvant (0.1 mL) into the rat's right foot pad. Behavioral reactions, pain threshold (latency of tail flick to heat stimulation) and local swelling severity (foot volume) were detected; the contents of β-endorphin (β-EP) and adrenocorticotropin (ACTH) were assayed with radioimmunoassay; and the expression of pro-opi-omelanocortin (POMC) mRNA in hypothalamus were determined with hybridization method. Results: The pain threshold was significantly enhanced by all the four kinds of acupuncture therapies, and the effects of EA and PI were more obvious (P0.05). The content of β-EP in the hypothalamus was obviously elevated by EA and FN (P0.05). The content of ACTH in hypothalamus was considerably elevated by PI (P<0.05), but not by the other three therapies. The expression of POMCmRNA in hypothalamus was significantly strengthened by EA and FN (P<0.01), but not by the other two therapies. Conclusion: EA, filiform needle, blood-letting and point-injection all can produce analgesic effect in adjuvant arthritis rats, the effect of EA and filiform needle may be related to their resultant increase of hypothalamic β-EP, and that of point-injection related to the increase of hypothalamic ACTH level.

  7. Study comparing sequential (neo-adjuvant) versus concurrent chemo-radiotherapy in patients with squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Okawa, Tomohiko; Karasawa, Kumiko; Kaneyasu, Yuko; Tanaka, Makiko; Kita-Okawa, Midori; Ishii, Tetsuo [Tokyo Women`s Medical Coll. (Japan)

    1994-11-01

    Radiotherapy combined with chemotherapy is still used for standard treatment in patients with locally advanced unresectable cancer. A study was undertaken to compare a sequential (neo-adjuvant) with a simultaneous (concurrent) chemotherapy and radiotherapy program. Neo-adjuvant chemotherapy with cisplatin (80 mg/m{sup 2} i.v. day 1) and 5FU (600 mg/m{sup 2} continuous i.v. day 1-5) every 3 weeks prior to definitive conventional radiotherapy (60-65 Gy), or cisplatin (20 mg/m{sup 2} i.v. day 1-5) and 5FU (250 mg/m{sup 2} continuous i.v. infusion. day 1-14) were given simultaneously for same radiotherapy. Complete response rate was 45% in the sequential treatment and 43% in the simultaneous arm. Leukopenia and other adverse effects were slightly more frequent in the simultaneous arm, but there were no significant differences. These results suggested that individualization of treatment planning and establishment of optimum treatment were most important for combination of chemotherapy and radiotherapy. (author).

  8. A COMPARATIVE EVALUATION OF DEXMEDETOMIDINE AND CLONIDINE AS ADJUVANTS TO LEVOBUPIVACAINE IN EPIDURAL ANAESTHESIA FOR LOWER LIMB ORTHOPAEDIC SURGERIES

    Directory of Open Access Journals (Sweden)

    Karthik

    2015-02-01

    and Fisher Exact test. The Statistical Software namely SAS 9.2,SPSS 15.0,Stata 10.1,MedCalc 9.0.1,Sysatat 12.0 and R environment ver.2.11.1 were also used for the analysis of the data and Microsoft word and Excel have been used to generate graphs,tables etc. The value of P 0.05. CONCLUSION: Dexmedetomidine is a better neuraxial adjuvant when compared to clonidine for providing early onset of sensory and motor blockade levels, adequate sedation and a prolonged post - operative analgesia with better success rate and increased patient satisfaction

  9. Fentanyl, dexmedetomidine, dexamethasone as adjuvant to local anesthetics in caudal analgesia in pediatrics: A comparative study

    Directory of Open Access Journals (Sweden)

    Elham M. El-Feky

    2015-04-01

    Conclusion: Both caudal dexmedetomidine and caudal dexamethasone added to local anesthetics are good alternatives in prolongation of postoperative analgesia compared to caudal local anesthetic alone or added to caudal fentanyl. Also they showed less side effects compared to caudal fentanyl.

  10. DEXMEDETOMIDINE AND CLONIDINE AS ADJUVANTS TO LEVOBUPIVACAINE IN SUPRACLAVICULAR BRACHIAL PLEXUS BLOCK: A COMPARATIVE RANDOMISED PROSPECTIVE CONTROLLED STUDY

    Directory of Open Access Journals (Sweden)

    Karthik

    2015-03-01

    Full Text Available BACKGROUND: There are always efforts to find better and safer local anaesthetics along with adjuvants for supraclavicular brachial plexus block. Levobupivacaine, has strongly emerged as a safer alternative for regional anesthesia than its racemic sibling, bupivacaine. Alpha 2 agonists are combined with local anaesthetics to improve the quality of regional anesthesia. AIMS AND OBJECTIVES: This study was conducted to evaluate and compare the onset, duration of sensory and motor blockade along with the duration of analges ia between dexmedetomidine and clonidine when administered along with 0.5% levobupivacaine in supraclavicular brachial plexus block for upper limb orthopaedic surgeries. MATERIALS AND METHODS: A prospective randomized study was carried out in the departmen t of Anaesthesia at Rajarajeswari Medical College and Hospital which included 50 adult patients between the ages of 20 and 50 years (of ASA I/II grade who underwent upper limb orthopaedic surgeries. The patients were randomly allocated into two groups; le vobupivacaine + dexmedetomidine (LD and levobupivacaine + clonidine (LC, comprising of 25 patients each. Group LD was administered 30 ml of 0.5% levobupivacaine and 1μg/kg of dexmedetomidine, while group LC received admixture of 30 ml of 0.5% levobupivac aine and 1 μg/kg of Clonidine. Onset, duration of sensory and motor blockade and duration of analgesia were observed. STATISTICAL ANALYSIS: Statistical analysis was done using student t test, chi - square test and Fisher Exact test. The Statistical Software namely SAS 9.2, SPSS 15.0, Stata 10.1, MedCalc 9.0.1, Sysatat 12.0 and R environment ver.2.11.1 were also used for the analysis of the data and Microsoft word and Excel have been used to generate graphs, tables etc. The value of P <0.05 was considered significant and P < 0.001 as highly significant. RESULTS: The onset of sensory and motor blockade was faster in Group LD when compared to Group LC. The duration of sensory

  11. Less gastrointestinal toxicity after adjuvant radiotherapy on a small pelvic field compared to a standard pelvic field in patients with endometrial carcinoma

    NARCIS (Netherlands)

    de Jong, Renske A.; Pras, Elisabeth; Boezen, H. Marike; van der Zee, Ate G. J.; Mourits, Marian J. E.; Arts, Henriette J. G.; Aalders, Jan G.; Slot, Annerie; Timmer, Paul R.; Hollema, Harry; Nijman, Hans W.

    2012-01-01

    Objective: Radiotherapy is associated with short-term and long-term morbidity. This study compared toxicity rates among patients with endometrial carcinoma (EC) treated with adjuvant external beam radiation therapy (EBRT) on a small pelvic field (SmPF) in comparison with a standard pelvic field (StP

  12. Comparative Safety and Efficacy Profile of a Novel Oil in Water Vaccine Adjuvant Comprising Vitamins A and E and a Catechin in Protective Anti-Influenza Immunity

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    Sapna Patel

    2017-05-01

    Full Text Available Non-replicating vaccines, such as those based on recombinant proteins, require adjuvants and delivery systems, which have thus far depended on mimicking pathogen danger signals and strong pro-inflammatory responses. In search of a safer and more efficacious alternative, we tested whether vaccinations with influenza recombinant hemagglutinin (HA mixed with a novel vegetable oil in water emulsion adjuvant (Natural Immune-enhancing Delivery System, NIDS, based on the immune-enhancing synergy of vitamins A and E and a catechin, could protect against intra-nasal challenge with live influenza virus. Vaccinations of inbred Brag Albino strain c (BALB/c mice, with HA mixed with NIDS compared to other adjuvants, i.e., a squalene oil in water emulsion (Sq. oil, and the Toll Like Receptor 3 (TLR3 agonist Poly (I:C, induced significantly lower select innate pro-inflammatory responses in serum, but induced significantly higher adaptive antibody and splenic T Helper 1 (TH1 or TH2, but not TH17, responses. Vaccinations with NIDS protected against infection, as measured by clinical scores, lung viral loads, and serum hemagglutination inhibition titers. The NIDS exhibited a strong dose sparing effect and the adjuvant action of NIDS was intact in the outbred CD1 mice. Importantly, vaccinations with the Sq. oil, but not NIDS, induced a significantly higher Serum Amyloid P component, an acute phase reactant secreted by hepatocytes, and total serum IgE. Thus, the NIDS may be used as a clinically safer and more efficacious vaccine adjuvant against influenza, and potentially other infectious diseases.

  13. Adjuvant radiation therapy compared with cyclic chemotherapy in patients with mammary carcinoma. II. Changes of mitogen responses of blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Strender, L.E.; Blomgren, H.; Wasserman, J.; Petrini, B.; Baral, E. (Karolinska Sjukhuset, Stockholm (Sweden))

    1981-01-01

    Blood lymphocyte reactivity to purified protein derivative of tuberculin (PPD) and phytohaemagglutinin (PHA) was examined in 62 patients with breast carcinoma who received postoperative adjuvant radiation therapy or cyclic chemotherapy with chlorambucil, methotrexate and 5-fluorouracil. Both treatments impaired the immunologic reactivity of blood lymphocytes as measured by PPD and PHA stimulation in vitro. Radiation therapy seemed to cause more profound and protracted suppression of the PPD response than chemotherapy.

  14. INTRATHECAL BUPRENORPHINE, CLONIDINE AND FENTANYL AS ADJUVANTS TO 0.5% HYPERBARIC BUPIVACAINE IN LOWER ABDOMINAL AND LOWER LIMB SURGERIES: A PROSPECTIVE, RANDOMIZED AND COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Rashmi

    2015-06-01

    Full Text Available BACKGROUND: Among all the spinal adjuvants, clonidine, an alpha - 2 agonist has the ability to alleviate both the somatic and visceral pain and is more potent at spinal site, favoring its neuraxial administration. OBJECTIVE: This study was done to compare the onset and duration of sensory and motor blocks, duration of analgesia, haemodynamic and adverse effects of Clonidine, buprenorhine and fentanyl used intrathecally with hyperbaric 0.5% bupuvacaine. SETTINGS & DESIGN: This prospective, randomized and comparative study included 90 ASA class 1 & 2 patients undergoing lower abdominal and lower limb surgeries under spinal anesthesia after approval from hospital ethics committee with written i nformed consent of patients. MATERIALS AND METHOD S: Patients were randomly allocated into three groups (n=30 and received 50μg of clonidine, 25μg of fentanyl and 75μg of buprenorphine respectively in group BC,BF and BB as adjuvants to 15mg of 0.5% hyperba ric bupivacaine (3.0ml. The onset time and duration of sensory and motor block, duration of analgesia, haemodynamic changes and side effects were recorded. RESULTS: The onset time of motor block and durations of sensory, motor blockade and analgesia were prolonged in - group BC as compared to group BF and BB (P.05. Group BC had lower heart rate and mean blood pressure and higher sedation score. CONCLUSION: Intr athecal Clonidine in a dose of 50μg is an effective adjuvant to local anesthetics in neuraxial blocks despite mild sedation and haemodynamic variations.

  15. A role for dZIP89B in Drosophila dietary zinc uptake reveals additional complexity in the zinc absorption process.

    Science.gov (United States)

    Richards, Christopher D; Warr, Coral G; Burke, Richard

    2015-12-01

    Dietary zinc is the principal source of zinc in eukaryotes, with its uptake and distribution controlled by a complex network of numerous membrane-spanning transport proteins. Dietary absorption is achieved by members of the SLC39A (ZIP) gene family, which encode proteins that are generally responsible for the movement of zinc into the cytosol. ZIP4 is thought to be the primary mammalian zinc uptake gene in the small intestine, with mutations in this gene causing the zinc deficiency disease Acrodermatitis enteropathica. In Drosophila, dual knockdown of the major dietary zinc uptake genes dZIP42C.1 (dZIP1) and dZIP42C.2 (dZIP2) results in a severe sensitivity to zinc-deficient media. However, the symptoms associated with ZIP4 loss can be reversed by zinc supplementation and dZIP42C.1 and 2 knockdown has minimal effect under normal dietary conditions, suggesting that additional pathways for zinc absorption exist in both mammals and flies. This study provides evidence that dZIP89B is an ideal candidate for this role in Drosophila, encoding a low-affinity zinc uptake transporter active in the posterior midgut. Flies lacking dZIP89B, while viable and apparently healthy, show indications of low midgut zinc levels, including reduced metallothionein B expression and compensatory up-regulation of dZIP42C.1 and 2. Furthermore dZIP89B mutants display a dramatic resistance to toxic dietary zinc levels which is abrogated by midgut-specific restoration of dZIP89B activity. We postulate that dZIP89B works in concert with the closely related dZIP42C.1 and 2 to ensure optimal zinc absorption under a range of dietary conditions.

  16. Comparing adjuvanted H28 and modified vaccinia virus ankara expressingH28 in a mouse and a non-human primate tuberculosis model.

    Directory of Open Access Journals (Sweden)

    Rolf Billeskov

    Full Text Available Here we report for the first time on the immunogenicity and protective efficacy of a vaccine strategy involving the adjuvanted fusion protein "H28" (consisting of Ag85B-TB10.4-Rv2660c and Modified Vaccinia Virus Ankara expressing H28. We show that a heterologous prime-boost regimen involving priming with H28 in a Th1 adjuvant followed by boosting with H28 expressed by MVA (H28/MVA28 induced the highest percentage of IFN-γ expressing T cells, the highest production of IFN-γ per single cell and the highest induction of CD8 T cells compared to either of the vaccines given alone. In contrast, in mice vaccinated with adjuvanted recombinant H28 alone (H28/H28 we observed the highest production of IL-2 per single cell and the highest frequency of antigen specific TNF-α/IL-2 expressing CD4 T cells pre and post infection. Interestingly, TNF-α/IL-2 expressing central memory-like CD4 T cells showed a significant positive correlation with protection at week 6 post infection, whereas the opposite was observed for post infection CD4 T cells producing only IFN-γ. Moreover, as a BCG booster vaccine in a clinically relevant non-human primate TB model, the H28/H28 vaccine strategy induced a slightly more prominent reduction of clinical disease and pathology for up to one year post infection compared to H28/MVA28. Taken together, our data showed that the adjuvanted subunit and MVA strategies led to different T cell subset combinations pre and post infection and that TNF-α/IL-2 double producing but not IFN-γ single producing CD4 T cell subsets correlated with protection in the mouse TB model. Moreover, our data demonstrated that the H28 vaccine antigen was able to induce strong protection in both a mouse and a non-human primate TB model.

  17. Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651.

    Science.gov (United States)

    Goorin, Allen M; Schwartzentruber, Douglas J; Devidas, Meenakshi; Gebhardt, Mark C; Ayala, Alberto G; Harris, Michael B; Helman, Lee J; Grier, Holcombe E; Link, Michael P

    2003-04-15

    Successful therapeutic interventions to prevent disease progression in patients with nonmetastatic osteosarcoma have included surgery with adjuvant chemotherapy. Presurgical chemotherapy has been advocated for these patients because of putative improvement in event-free survival (EFS). The advantages of presurgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy. The contribution of chemotherapy and surgery timing has not been tested rigorously. Between 1986 and 1993, we conducted a prospective trial in patients with nonmetastatic osteosarcoma who were assigned randomly to immediate surgery or presurgical chemotherapy. Except for the timing of surgery (week 0 or 10), patients received 44 weeks of identical combination chemotherapy that included high-dose methotrexate with leucovorin rescue, doxorubicin, cisplatin, bleomycin, cyclophosphamide, and dactinomycin. One hundred six patients were enrolled onto this study. Six were excluded from analysis. Of the remaining 100 patients, 45 were randomly assigned to immediate chemotherapy, and 55 were randomly assigned to immediate surgery. Sixty-seven patients remain disease-free. At 5 years, the projected EFS +/- SE is 65% +/- 6% (69% +/- 8% for immediate surgery and 61% +/- 8% for presurgical chemotherapy; P =.8). The treatment arms had similar incidence of limb salvage (55% for immediate surgery and 50% for presurgical chemotherapy). Chemotherapy was effective in both treatment groups. There was no advantage in EFS for patients given presurgical chemotherapy.

  18. Peptide-pulsed dendritic cells have superior ability to induce immune-mediated tissue destruction compared to peptide with adjuvant.

    Directory of Open Access Journals (Sweden)

    Dilan Dissanayake

    Full Text Available Vaccines for cancer immunotherapy are of interest but in general have not yet achieved the desired therapeutic efficacy in clinical trials. We present here a novel model to evaluate vaccine strategies by following tissue destruction in a transgenic model, where a defined antigen is expressed on pancreatic islets. We found that the transfer of syngeneic antigen-pulsed dendritic cells (DCs resulted in autoimmune cytotoxic T-lymphocyte activation that was not observed following vaccinations that were based on peptides and adjuvants. Importantly, the induction of diabetes by DC transfer is dependent upon the maturation of DCs prior to transfer. Furthermore, diabetes induction only occurred if DCs were pulsed with the immunodominant epitope in addition to at least one other peptide, suggesting greater cytolytic activity upon engagement of multiple T-cell specificities. While the tumor environment undoubtedly will be more complex than healthy tissue, the insights gained through this model provide useful information on variables that can affect CD8-mediated tissue cytolysis in vivo.

  19. Accuracy of MRI for prediction of response to neo-adjuvant chemotherapy in triple negative breast cancer compared to other subtypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Gaurav J Bansal

    2016-01-01

    Full Text Available Purpose: The aim of this study was to compare the accuracy of magnetic resonance imaging (MRI for the prediction of response to neo-adjuvant chemotherapy in triple negative (TN breast cancer, with respect to other subtypes. Materials and Methods: There were a total of 1610 breast cancers diagnosed between March 2009 and August 2014, out of which 82 patients underwent MRI before and after neo-adjuvant chemotherapy but just before surgery. TN cancers were analyzed with respect to others subtypes. Accuracy of MRI for prediction of pathological complete response was compared between different subtypes by obtaining receiver operating characteristic (ROC curves. The Statistical Package for the Social Sciences version 21 was used for all data analysis, with P value of 0.05 as statistically significant. Results: Out of 82 patients, 29 were luminal (HR+/HER2−, 23 were TN (HR−, HER2−, 11 were HER2 positive (HR−, HER2+, and 19 were of hybrid subtype (HR+/HER2+. TN cancers presented as masses on the pre-chemotherapy MRI scan, were grade 3 on histopathology, and showed concentric shrinkage following chemotherapy. TN cancers were more likely to have both imaging and pathological complete response following chemotherapy (P = 0.055 in contrast to luminal cancers, which show residual cancer. ROC curves were constructed for the prediction of pathological complete response with MRI. For the TN subgroup, MR had a sensitivity of 0.745 and specificity of 0.700 (P = 0.035, with an area under curve of 0.745 (95% confidence interval: 0.526–0.965, which was significantly better compared to other subtypes. Conclusion: TN breast cancers present as masses and show concentric shrinkage following chemotherapy. MRI is most accurate in predicting response to chemotherapy in the TN group, compared to others subtypes. MRI underestimates residual disease in luminal cancers.

  20. Using Qualitative Comparative Analysis of Key Informant Interviews in Health Services Research: Enhancing a Study of Adjuvant Therapy Use in Breast Cancer Care.

    Science.gov (United States)

    McAlearney, Ann Scheck; Walker, Daniel; Moss, Alexandra D; Bickell, Nina A

    2016-04-01

    Qualitative comparative analysis (QCA) is a methodology created to address causal complexity in social sciences research by preserving the objectivity of quantitative data analysis without losing detail inherent in qualitative research. However, its use in health services research (HSR) is limited, and questions remain about its application in this context. To explore the strengths and weaknesses of using QCA for HSR. Using data from semistructured interviews conducted as part of a multiple case study about adjuvant treatment underuse among underserved breast cancer patients, findings were compared using qualitative approaches with and without QCA to identify strengths, challenges, and opportunities presented by QCA. Ninety administrative and clinical key informants interviewed across 10 NYC area safety net hospitals. Transcribed interviews were coded by 3 investigators using an iterative and interactive approach. Codes were calibrated for QCA, as well as examined using qualitative analysis without QCA. Relative to traditional qualitative analysis, QCA strengths include: (1) addressing causal complexity, (2) results presentation as pathways as opposed to a list, (3) identification of necessary conditions, (4) the option of fuzzy-set calibrations, and (5) QCA-specific parameters of fit that allow researchers to compare outcome pathways. Weaknesses include: (1) few guidelines and examples exist for calibrating interview data, (2) not designed to create predictive models, and (3) unidirectionality. Through its presentation of results as pathways, QCA can highlight factors most important for production of an outcome. This strength can yield unique benefits for HSR not available through other methods.

  1. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial) - a randomized, multidisciplinary, multinational phase III trial

    DEFF Research Database (Denmark)

    Stein, A.; Arnold, D.; Bridgewater, J.;

    2015-01-01

    selected the combination of gemcitabine and cisplatin for 24 weeks as investigational treatment. Based on adjuvant trials in pancreatic cancer with comparable postoperative recovery time, inclusion of patients within a maximum interval of 16 weeks between surgery and start of chemotherapy was stipulated...

  2. Adjuvants for Animal Vaccines.

    Science.gov (United States)

    Burakova, Yulia; Madera, Rachel; McVey, Scott; Schlup, John R; Shi, Jishu

    2017-06-15

    Vaccines are essential tools for the prevention and control of infectious diseases in animals. One of the most important steps in vaccine development is the selection of a suitable adjuvant. The focus of this review is the adjuvants used in vaccines for animals. We will discuss current commercial adjuvants and experimental formulations with attention to mineral salts, emulsions, bacterial-derived components, saponins, and several other immunoactive compounds. In addition, we will also examine the mechanisms of action for different adjuvants, examples of adjuvant combinations in one vaccine formulation, and challenges in the research and development of veterinary vaccine adjuvants.

  3. A COMPARATIVE STUDY OF THE DIFFERENT DOSES OF MAGNESIUM SULPHATE AND FENTANYL AS ADJUVANTS TO BUPIVACAINE [0.5% HEAVY] FOR LOWER ABDOMINAL SURGERIES UNDER SUBARACHNOID BLOCK

    Directory of Open Access Journals (Sweden)

    Syed Ali

    2016-04-01

    Full Text Available BACKGROUND Spinal anaesthesia is the most commonly used technique for infraumbilical surgeries and it has some disadvantages, such as a short duration of motor blockade and post-operative analgesia. This study was designed to evaluate the effects of additive agents of fentanyl and magnesium sulphate along with Bupivacaine for prolongation of analgesia and motor blockade during spinal anaesthesia for infraumbilical surgeries. METHODS This study was conducted in 60 patients of both sexes of ASA physical status I and II scheduled for infraumbilical surgeries. Patients were randomly divided into two groups and were given the drugs intrathecally as per group distribution; Group BFbupivacaine 15 mg (0.5% heavy with fentanyl 25 μg, Group BM-bupivacaine 15 mg (0.5% heavy with magnesium 100 mg intrathecal. RESULTS There was a similar increase in duration of analgesia in Group BF (378.21 min. as compared to Group BM (331.12 min.. In Group (BF, all haemodynamic parameters are decreased by more than 19%. There was an increase in duration of motor blockade more in Group (BF compared to Group (BM. CONCLUSION In conclusion, (100 mg magnesium sulphate or (25 μg fentanyl as adjuvants with bupivacaine to spinal anaesthesia. Both drugs are significantly prolonging the duration of both sensory block and analgesia, but magnesium sulphate provides better haemodynamic stability than fentanyl.

  4. Comparative study of two doses of intrathecal dexmedetomidine as adjuvant with low dose hyperbaric bupivacaine in ambulatory perianal surgeries: A prospective randomised controlled study

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    K Sudheesh

    2015-01-01

    Full Text Available Background and Aims: Dexmedetomidine (DMT, as intrathecal adjuvant has been shown to successfully prolong duration of analgesia but delay the motor recovery. Hence, this study was designed to find out the dose of DMT which can provide satisfactory analgesia without prolonging motor block. Methods: A total of 50 patients scheduled for elective perianal surgeries were randomly allocated to Groups C or D (n = 25. Group D received hyperbaric bupivacaine 0.5% 4 mg + DMT 5 μg and Group C received hyperbaric bupivacaine 0.5% 4 mg + DMT 3 μg intrathecally. Onset and duration of sensory and motor blockade, duration of analgesia, time for ambulation and first urination were recorded. Adverse effects if any were noted. Results: Demographic characters, duration of surgery were comparable. The onset of sensory block to S1 was 9.61 ± 5.53 min in Group C compared to 7.69 ± 4.80 min in Group D (P = 0.35. Duration of sensory (145.28 ± 83.17 min – C, 167.85 ± 93.75 min – D, P = 0.5 and motor block (170.53 ± 73.44 min – C, 196.14 ± 84.28 min, P = 0.39 were comparable. Duration of analgesia (337.86 ± 105.11 min – C, 340.78 ± 101.81 min – D, P = 0.9 and time for ambulation (252.46 ± 93.72 min – C, 253.64 ± 88.04 min – D, P = 0.97 were also comparable. One patient in each group had urinary retention requiring catheterization. No other side effects were observed. Conclusion: Intrathecal DMT 3 μg dose does not produce faster ambulation compared to intrathecal DMT 5 μg though it produces comparable duration of analgesia for perianal surgeries.

  5. One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent; Jensen, Maj-Britt; Elversang, Johanna

    2013-01-01

    We report the long-term results of a randomised trial comparing tamoxifen with tamoxifen plus cyclophosphamide, methotrexate and fluorouracil (CMF) in postmenopausal high-risk breast cancer patients. In addition, we analyse the prognostic and predictive value of centrally assessed subtypes....

  6. A Comparative Phase I Study of Combination, Homologous Subtype-C DNA, MVA, and Env gp140 Protein/Adjuvant HIV Vaccines in Two Immunization Regimes

    Science.gov (United States)

    Joseph, Sarah; Quinn, Killian; Greenwood, Aldona; Cope, Alethea V.; McKay, Paul F.; Hayes, Peter J.; Kopycinski, Jakub T.; Gilmour, Jill; Miller, Aleisha N.; Geldmacher, Christof; Nadai, Yuka; Ahmed, Mohamed I. M.; Montefiori, David C.; Dally, Len; Bouliotis, George; Lewis, David J. M.; Tatoud, Roger; Wagner, Ralf; Esteban, Mariano; Shattock, Robin J.; McCormack, Sheena; Weber, Jonathan

    2017-01-01

    There remains an urgent need for a prophylactic HIV vaccine. We compared combined MVA and adjuvanted gp140 to sequential MVA/gp140 after DNA priming. We expected Env-specific CD4+ T-cells after DNA and MVA priming, and Env-binding antibodies in 100% individuals after boosting with gp140 and that combined vaccines would not compromise safety and might augment immunogenicity. Forty volunteers were primed three times with DNA plasmids encoding (CN54) env and (ZM96) gag-pol-nef at 0, 4 and 8 weeks then boosted with MVA-C (CN54 env and gag-pol-nef) and glucopyranosyl lipid adjuvant—aqueous formulation (GLA-AF) adjuvanted CN54gp140. They were randomised to receive them in combination at the same visit at 16 and 20 weeks (accelerated) or sequentially with MVA-C at 16, 20, and GLA-AF/gp140 at 24 and 28 weeks (standard). All vaccinations were intramuscular. Primary outcomes included ≥grade 3 safety events and the titer of CN54gp140-specific binding IgG. Other outcomes included neutralization, binding antibody specificity and T-cell responses. Two participants experienced asymptomatic ≥grade 3 transaminitis leading to discontinuation of vaccinations, and three had grade 3 solicited local or systemic reactions. A total of 100% made anti-CN54gp140 IgG and combining vaccines did not significantly alter the response; geometric mean titer 6424 (accelerated) and 6578 (standard); neutralization of MW965.2 Tier 1 pseudovirus was superior in the standard group (82 versus 45% responders, p = 0.04). T-cell ELISpot responses were CD4+ and Env-dominant; 85 and 82% responding in the accelerated and standard groups, respectively. Vaccine-induced IgG responses targeted multiple regions within gp120 with the V3 region most immunodominant and no differences between groups detected. Combining MVA and gp140 vaccines did not result in increased adverse events and did not significantly impact upon the titer of Env-specific binding antibodies, which were seen in 100% individuals

  7. Adjuvants for malaria vaccines.

    Science.gov (United States)

    Coler, R N; Carter, D; Friede, M; Reed, S G

    2009-09-01

    There is a renewed enthusiasm about subunit vaccines for malaria coincident with the formation of new alliances and partnerships raising international public awareness, attracting increased resources and the re-focusing of research programs on adjuvant development for infectious disease vaccines. It is generally accepted that subunit vaccines for malaria will require adjuvants to induce protective immune responses, and availability of suitable adjuvants has in the past been a barrier to the development of malaria vaccines. Several novel adjuvants are now in licensed products or in late stage clinical development, while several others are in the earlier development pipeline. Successful vaccine development requires knowing which adjuvants to use and knowing how to formulate adjuvants and antigens to achieve stable, safe, and immunogenic vaccines. For the majority of vaccine researchers this information is not readily available, nor is access to well-characterized adjuvants. In this minireview, we outline the current state of adjuvant research and development as it pertains to effective malaria vaccines.

  8. Comparative pharmacoeconomics and efficacy analysis of a new antibiotic adjuvant entity and piperacillin-tazobactam for the management of intra-abdominal infections: A retrospective study

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    Sandip Jadhav

    2016-01-01

    Full Text Available Objective: To analyze the comparative efficacy of piperacillin-tazobactam (PIP-TAZ and ceftriaxone-sulbactam with adjuvant (CSA in the treatment of intra-abdominal infections (IAIs and to assess the costs associated with respective therapies. Methods: The present study analyzed the data collected from 94 IAI patients treated at a tertiary-care hospital. Patient characteristics, infection types, surgical procedures, antibiotic therapies, treatment durations were recorded and overall cost involved in the infections management was estimated in Indian rupee. Results: In total, 46 patients received PIP-TAZ and 48 patients received CSA. The clinical cure was seen in 39.13% patients of PIP-TAZ group and 62.50% patients of CSA group. The patients diagnosed with mixed culture (Gram-positive and negative infections, needed additional cover of clindamycin to achieve clinical success. The failure patients from PIP-TAZ group were shifted to meropenem therapy. For the patients where meropenem and CSA therapy failed, colistin was given as an additional cover. Comparative cost expenditure analysis of the two drug treatment groups revealed that, the overall treatment cost for patients cured with empirical PIP-TAZ group was 51.79% more than that of CSA therapy. The strongest predictor of the increase in treatment costs was clinical failure. Similar trends were maintained for the patients cured with clindamycin additional therapy and change of therapy, with PIP-TAZ group accounting 36.11% and 39.99% more expenditure than CSA group. Conclusions: This study demonstrates that CSA has comparatively higher efficacy as compared to PIP-TAZ when used along with metronidazole in patients with different types of IAIs. Pharmacoeconomic analysis clearly shows that starting appropriate empirical antibiotic therapy has a large impact on the cost of treatment in management of IAIs and selection of CSA, can significantly reduce the cost involved in the treatment.

  9. Trends in vaccine adjuvants

    NARCIS (Netherlands)

    Schijns, V.E.J.C.; Lavelle, E.C.

    2011-01-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a

  10. COMPARATIVE STUDY OF HYPERBARIC BUPIVACAINE AND PLAIN ROPIVACAINE WITH FENTANYL AS AN ADJUVANT FOR SPINAL ANAESTHESIA IN CEASAREAN SECTION

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    Vindhya

    2014-07-01

    Full Text Available : Spinal anaesthesia is very popular for cesarean section and currently both hyperbaric and plain solutions of local anaesthesia along with opioids are used. Difference in the baricity can affect the intrathecal distribution of local anaesthetics. AIM: We compared the effects of intrathecal hyperbaric (heavy 0.5% bupivacaine and isobaric (plain 0.75%ropivacaine combined with 25micro grams fentanyl regarding the degree of sensory and motor block, quality of intraoperative anaesthesia, side effects and post-operative analgesia in patients undergoing cesarean section by doing a randomized controlled study. MATERIALS AND METHODS: Sixty women undergoing caesarean section were randomized into two groups, Group BF (n=30, group RF (n= 30. Group BF received 10 mg (2 ml of 0.5% hyperbaric bupivacaine with 25µgs of preservative free fentanyl and Group RF received 15mgs (2ml 0.75% plain Ropivacaine (isobaric with 25µgs of fentanyl for spinal anaesthesia. In case of insufficient blocks both the groups were supplemented with analgesic dose of ketamine. RESULTS: No difference was observed in onset time, highest level and recovery of sensory block. Recovery of motor block was slightly prolonged in RF group. The incidence of insufficient block requiring ketamine supplementation and duration of postoperative analgesia was same in both groups. The side effects were also similar in both the groups except for hypotension lower systolic pressure in BF group. The neonatal outcome was unaffected. CONCLUSION: In this study we did not find any difference in the two groups despite difference in density suggesting that the spread of spinal solution is not dependent on density in patients undergoing caesarean section.

  11. Comparative efficacy of 5flourouracil/calcium leucovorine versus 5flourouracil/calcium leucovorine plus oxaliplatin in the adjuvant treatment of colonic carcinoma in Kashmir

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    Hamid Deva Shaiq

    2013-01-01

    Full Text Available Aim: This prospective, randomized comparative study conducted in Kashmir evaluated the clinical profile of colonic carcinoma and the efficacy, side effects and survival advantage of adjuvant treatment with 5FU/CLV versus FOLFOX7. Materials and Methods: Between 2007 and 2009, the clinical profiles of 50 patients enrolled and randomized equally into Arm A receiving 5FU/CLV alone (Mayo Clinic Regimen and Arm B receiving the FOLFOX7 regimen (including oxaliplatin were evaluated. Results: Majority of the patients were in the 5 th and 6 th decade of life (males 70% versus females 30%, and most were from urban dwellings. Consumption of red meat, obesity and physical inactivity were common risk factors. A family history of colonic carcinoma was reported in 12% of the patients. Event-free and disease-free survival for the two arms were: Arm A - 12.8 ± 5 months and 14.2 ± 6 months; Arm B - 13.0 ± 6.7 months and 13.1 ± 6 months, respectively. Treatment-related morbidity was significant in Arm B whereas general well being and surrogate laboratory markers including a hemogram, favored Arm A. Conclusion: The clinical profile, risk factors and familial predisposition of Kashmiri colonic carcinoma patients matches that of colon cancer patients elsewhere. There was no added survival advantage by adding oxaliplatin to 5FU and CLV. Although the interim results showed that the Mayo Clinic Regimen has a better total survival advantage compared with the FOLFOX7 regimen, the results were not statistically significant. The Mayo Clinic Regimen was better than the FOLFOX7 regimen in terms of the toxicity profile. However, this finding needs to be studied further. The main idea of conducting this study was to reveal that there is no added advantage of adding oxaliplatin to 5FU and CLV, thereby (a reducing the toxicity (b and lowering cost of therapy.

  12. COMPARATIVE EVALUATION OF CAUDAL FENTANYL AND CLONIDINE AS ADJUVANT TO BUPIVACAINE FOR POST- OPERATIVE ANALGESIA IN PEDIATRIC GENITOURINARY AND INGUINAL SURGERIES

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    Vikas Kumar

    2014-08-01

    Full Text Available Post-operative analgesia in children is a challenging task before the anesthesiologist. Caudal analgesia is an accepted and popular method of providing intraoperative and postoperative analgesia for genitourinary and inguinal surgeries in children. Because of short duration of action of Bupivacaine, various adjuncts have been tried by many anesthesiologists. Fentanyl and Clonidine are used along with local anesthetics to prolong duration of analgesia. Hence we are comparing 1 mcg/kg of Fentanyl and 1 mcg/kg of Clonidine as adjuvants to 0.25% bupivacaine at a volume of 0.75 ml/kg in children undergoing genitourinary and inguinal surgeries. AIMS AND OBJECTIVES: To compare the efficacy of Fentanyl and Clonidine as adjuncts to Bupivacaine for postoperative analgesia in pediatric patients and to evaluate the sequel and side effects of both. MATERIALS AND METHODS: Study design – Comparative randomized controlled study. Sample size: 120 children aged between 2-7 years posted for genitourinary and inguinal surgeries. Group I (B received 0.75 ml/kg of 0.25% Bupivacaine alone caudally. Group II (BF received 0.75 ml/kg of 0.25% Bupivacaine and 1 µg/kg Fentanyl caudally. Group III (BC received 0.75 ml/kg of 0.25% Bupivacaine and 1 µg/kg Clonidine caudally. Postoperatively the duration of analgesia, motor blockade and sedation was assessed by Modified Objective Pain Scale, Ramsay Sedation Score and modified Bromage scale respectively. Side effects and complications, if present were recorded. Tests used for statistical analysis were Fishers exact test and student t test. RESULTS: The mean duration of analgesia in group BC (601.5 + 60.17 minutes was much higher than group BF and B but with side effect of sedation. We observed that there was a statistically increased duration of analgesia in Clonidine group as compared to Fentanyl and plain Bupivacaine group with no difference in duration of motor blockade. There was increased sedation in group BC. Group BF

  13. [Influenza vaccine and adjuvant].

    Science.gov (United States)

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine.

  14. Adjuvants for allergy vaccines

    National Research Council Canada - National Science Library

    Moingeon, Philippe

    2012-01-01

    .... Aluminum hydroxide or calcium phosphate are broadly used as adjuvants for subcutaneous allergy vaccines, whereas commercial sublingual vaccines rely upon high doses of aqueous allergen extracts...

  15. Adjuvant therapy in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Paula Ghaneh; John Slavin; Robert Sutton; Mark Hartley; John P Neoptolemos

    2001-01-01

    The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic csncer, leading to a drsmatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone.The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

  16. MAGNESIUM SULPHATE VS CLONIDINE AS AN ADJUVANT TO 0.5% BUPIVACAINE IN EPIDURAL ANAESTHESIA FOR PATIENTS UNDERGOING LOWER LIMB SURGERIES: A COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Anand Masih

    2015-09-01

    Full Text Available Epidural anesthesia is a safe and inexpensive technique with the advantage of providing surgical anesthesia and prolonged postoperative pain relief. To address the problems of limited duration of action and to improve the quality of analgesia intra - operatively and postoperatively, various adjuvants have been added to bupivacaine. The present study is designed to evaluate the effect of magnesium sulphate vs clonidine as an adjunct to 0.5% Bupivacaine in epidural anesthesia for patients undergoing lower limb surgeries in terms of onset, duration and degree of sensory and motor block, sedation and pain. 90 patients of age group 18 - 60 years of ASA grade I & II of either sex undergoing lower limb surgeries were included in this prospective study who were randomly allocated into three groups . Group A received bupivacaine 0.5%(19ml +normal saline 0.9% (1.0ml, Group B received bupivacaine 0.5%(19ml+magnesium sulphate 50mg dissolved in 0.9% normal saline (1.0ml and Group C received bupivacaine 0.5%(19ml +clonidine 150μgm(1.0ml. Assessments of sensory block were performed at 5, 10, 15, 20, 25, 30 min and then every 10 min until the return of normal sensation. . Assessment of motor block were performed immediately after the assessment of sensory block until the return of normal motor function. The onset and end of all degrees of motor blocks were assessed bilaterally according to the Modified Bromage scale. Duration of analgesia, patient’s satisfaction, duration of motor block and adverse effects were assessed and recorded. We concluded that co - administration of epidural magnesium sulphate 50 MG with bupivacaine 0.5% produces predictable rapid onset of surgical anesthesia without any side - effects, and addi tion of clonidine 150μgmto epidural bupivacaine 0.5% produces prolonged duration of anesthesia with sedation. The results of our study suggest that magnesium may be a useful alternative as an adjuvant to epidural bupivacaine as clonidine .

  17. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Adjuvant treatment for early epithelial ovarian cancer: results of two randomised clinical trials comparing cisplatin to no further treatment or chromic phosphate (32P). G.I.C.O.G.: Gruppo Interregionale Collaborativo in Ginecologia Oncologica.

    Science.gov (United States)

    Bolis, G; Colombo, N; Pecorelli, S; Torri, V; Marsoni, S; Bonazzi, C; Chiari, S; Favalli, G; Mangili, G; Presti, M

    1995-11-01

    From 1983 to 1990, 271 consecutive patients with stage I ovarian cancer entered two randomised trials, aimed at assessing the role of adjuvant chemotherapy after radical surgery in early stages of ovarian cancer. Trial I compared cisplatin (50 mg/m2 with repeated courses every 28 days for 6 cycles) to no further therapy in F.I.G.O. stage Ia & b Grade II-III patients; trial II compared cisplatin (same dose and schedule) to 32P in Iaii & bii and Ic patients. Both studies were multicentric and centrally randomized. Treatment was allocated by phone and stratified by center. All patients satisfying major eligibility criteria (histological and grade, no previous neoplasms) were analysed according to treatment allocated by randomisation. With a median observation time of 76 months, cisplatin significantly reduced the relapse rate by 65% (HR = 0.35; 95% CI = 0.14-0.89, p = 0.028; Cox Model) in trial I and 61% (HR = 0.39; 95% CI = 0.19-0.77, p = 0.007; Cox Model) in trial II. Survival was not significantly different (trial I - Kaplan-Meier overall 5-year survival: cisplatin = 88%, control = 82%, HR = 1.15; 95% CI = 0.44-2.98; p = 0.773; Cox Model); trial II - overall 5-year survival: cisplatin = 81%, 32P = 79%, HR = 0.72; 95% CI = 0.37-1.43; p = 0.354; Cox model). In both studies the risk of dying after relapse increased for patients originally randomized to the cisplatin arms: in trial I, 6 of 7 patients in the cisplatin relapsed arm and died of tumor compared with 8 of 14 patients in the control arm. In trial II 11 of 12 patients on cisplatin, and 18 of 26 on 32P succumbed to tumor recurrence. Adjuvant cisplatin treatment in early ovarian cancer significantly prevents relapse in comparison to 32P in stage IC patients or to no immediate treatment in earlier stage women. The impact of cisplatin adjuvant treatment on survival remains, however, unclear.

  19. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    Science.gov (United States)

    Payne, Richard; McDonald, David; Byrne, Scott

    2015-10-01

    Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

  20. Adjuvants for allergy vaccines.

    Science.gov (United States)

    Moingeon, Philippe

    2012-10-01

    Allergen-specific immunotherapy is currently performed via either the subcutaneous or sublingual routes as a treatment for type I (IgE dependent) allergies. Aluminum hydroxide or calcium phosphate are broadly used as adjuvants for subcutaneous allergy vaccines, whereas commercial sublingual vaccines rely upon high doses of aqueous allergen extracts in the absence of any immunopotentiator. Adjuvants to be included in the future in products for allergen specific immunotherapy should ideally enhance Th1 and CD4+ regulatory T cell responses. Imunomodulators impacting dendritic or T cell functions to induce IL10, IL12 and IFNγ production are being investigated in preclinical allergy models. Such candidate adjuvants encompass synthetic or biological immunopotentiators such as glucocorticoids, 1,25-dihydroxy vitamin D3, selected probiotic strains (e.g., Lactobacillus and Bifidobacterium species) as well as TLR2 (Pam3CSK4), TLR4 (monophosphoryl lipid A, synthetic lipid A analogs) or TLR9 (CpGs) ligands. Furthermore, the use of vector systems such as mucoadhesive particules, virus-like particles or liposomes are being considered to enhance allergen uptake by tolerogenic antigen presenting cells present in mucosal tissues.

  1. Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study

    DEFF Research Database (Denmark)

    Colleoni, Marco; Giobbie-Hurder, Anita; Regan, Meredith M

    2011-01-01

    Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged ov...

  2. A comparative study of dexmedetomidine and fentanyl as adjuvants to levobupivacaine for caudal analgesia in children undergoing lower limb orthopedic surgery

    Science.gov (United States)

    Elfawal, SM; Abdelaal, WA; Hosny, MR

    2016-01-01

    Background: Levobupivacaine is an effective local anesthetic agent with less systemic toxicity than racemic bupivacaine, but it has short postoperative analgesic duration. Dexmedetomidine and fentanyl are promising adjuncts to provide excellent and prolonged postoperative caudal analgesia. This study compared the effects of caudal levobupivacaine plus dexmedetomidine and levobupivacaine plus fentanyl for postoperative analgesia and sedation in children undergoing lower limb orthopedic surgery. Patients and Methods: Ninety children, whose age ranged from 1 to 7 years, American Society of Anesthesiologists I-II, undergoing orthopedic lower limb surgery under general anesthesia received caudal block for postoperative analgesia. The children were randomly allocated into three groups: Group L (control) received 0.75 ml/kg levobupivacaine 0.25% diluted in saline; Group LD received 0.75 ml/kg levobupivacaine 0.25% with dexmedetomidine 1 μg/kg; and Group LF received 0.75 ml/kg levobupivacaine 0.25% with fentanyl 1 μg/kg. Following the administration of the drugs; hemodynamic variables, the total anesthesia time, sedation score, Face, Legs, Activity, Cry, Consolability score, duration of analgesia, and side effects were recorded. Results: Demographically, all the groups were comparable, both the baseline and the intraoperative hemodynamic profile were similar in all groups. The mean duration of analgesia and the mean sedation score in the Group LD were significantly greater as compared to both the other groups. Conclusion: Dexmedetomidine may be a better additive to levobupivacaine than fentanyl for caudal postoperative analgesia, arousable sedation with comparable hemodynamic and side effect profile in children. PMID:27833486

  3. Carbohydrate-based immune adjuvants

    Science.gov (United States)

    Petrovsky, Nikolai; Cooper, Peter D

    2011-01-01

    The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage. PMID:21506649

  4. Adjuvant Therapy: Melanoma

    Directory of Open Access Journals (Sweden)

    Diwakar Davar

    2011-01-01

    Full Text Available With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4 monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway.

  5. A randomised phase III trial of adjuvant radio-chemotherapy comparing Irinotecan, 5FU and Leucovorin to 5FU and Leucovorin in patients with rectal cancer: a Hellenic Cooperative Oncology Group Study.

    Science.gov (United States)

    Kalofonos, H P; Bamias, A; Koutras, A; Papakostas, P; Basdanis, G; Samantas, E; Karina, M; Misailidou, D; Pisanidis, N; Pentheroudakis, G; Economopoulos, T; Papadimitriou, C; Skarlos, D V; Pectasides, D; Stavropoulos, M; Bafaloukos, D; Kardamakis, D; Karanikiotis, C; Vourli, G; Fountzilas, G

    2008-08-01

    The primary objective was to compare the 3-year survival of rectal cancer patients randomised postoperatively to irinotecan (IRI), Leucovorin (LV) and bolus 5-fluorouracil (5FU) or LV-bolus 5FU with radiotherapy. Secondary objectives included disease-free survival, local relapse and toxicity. The study included 321 eligible patients. The treatment consisted of weekly administration of IRI 80 mg/m(2) intravenously (IV), LV 200 mg/m(2) and 5FU 450 mg/m(2) bolus (arm A) versus LV 200 mg/m(2) and 5FU 450 mg/m(2) IV bolus (arm B). One cycle included four infusions and treatment was continued for a total of six cycles. The first cycle was followed by pelvic irradiation plus 5FU. There were no differences between the arms in 3-year overall, disease-free and local relapse-free survival. Grades 3 and 4 toxicity was similar in both the arms with the exception of leucopaenia, neutropaenia and alopecia, which were higher in the IRI arm. IRI added to adjuvant radiochemotherapy with LV and bolus 5FU was not shown to improve survival, whereas the incidence of severe leucopaenia was significantly higher in the IRI arm.

  6. Adjuvant therapies for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced (stage Ⅲ and selected stage Ⅱ) colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage Ⅱ disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.

  7. Characterization of the in situ immunological responses to vaccine adjuvants.

    Science.gov (United States)

    Horohov, D W; Dunham, J; Liu, C; Betancourt, A; Stewart, J C; Page, A E; Chambers, T M

    2015-03-15

    Adjuvants are included with many inactivated and some modified live vaccines to enhance immune responses to specific antigens. While early vaccines relied exclusively upon aluminum salts, still the major adjuvant used in human vaccines, other adjuvant products are used in veterinary medicine. In addition to enhancing antigen presentation, adjuvants can also enhance the development of specific immune responses. Thus, alum adjuvants often preferentially stimulate humoral immune responses. By contrast, lipid-based adjuvants are often more effective at stimulating cell-mediated immune responses. Metastim(®) is a lipid-based adjuvant reported to elicit both humoral and cellular immune responses, though the mechanism responsible for this activity remains unclear. In this study, we compared the ability of equine influenza virus vaccines containing either saline or Metastim(®) or an aluminum phosphate adjuvant to stimulate antigen presenting cell function in vivo. Six ponies were intradermally inoculated with inactivated equine influenza (KY97) mixed with either adjuvant or saline. Multiple sites were injected so that biopsies could be collected at different times post injection. The 4mm punch biopsies were formalin-fixed, paraffin-embedded, and stained with hematoxylin and eosin (H&E). Total RNA was isolated from 2mm punch biopsies for the determination of gene expression by real-time PCR. H&E staining revealed a variety of cells recruited to the injection sites, including lymphocytes, neutrophils, eosinophils and macrophages. Real-time PCR analysis of the injection site confirmed this cellular infiltration and identified increased expression of activation markers. Both vaccines also stimulated gene expressions of pro-inflammatory cytokines. The vaccine containing Metastim(®) elicited significantly higher gene expression of interferon-γ, IL-12, CD4 and CD83 compared to alum (psalt, there was also evidence of Th2 cytokine induction. Copyright © 2015 Elsevier B.V. All

  8. Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG Study

    Directory of Open Access Journals (Sweden)

    Arie Figer, Aviram Nissan, Adi Shani, Riva Borovick, Mariana Stiener, Mario Baras, Herbert R. Freund, Aaron Sulkes, Alexander Stojadinovic, Tamar Peretz

    2011-01-01

    Full Text Available Objective: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC. This study evaluates long-term (10-year outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV or 5-FU/Levamisole (5FU+LEV.Methods: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months.Results: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02 and gastrointestinal toxicity with 5FU+LV (p=0.03. Female patients treated with 5FU+LEV had improved overall survival.Conclusions: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset.

  9. Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG) Study

    Science.gov (United States)

    Figer, Arie; Nissan, Aviram; Shani, Adi; Borovick, Riva; Stiener, Mariana; Baras, Mario; Freund, Herbert R.; Sulkes, Aaron; Stojadinovic, Alexander; Peretz, Tamar

    2011-01-01

    Objective: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC). This study evaluates long-term (10-year) outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV) or 5-FU/Levamisole (5FU+LEV). Methods: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months. Results: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02) and gastrointestinal toxicity with 5FU+LV (p=0.03). Female patients treated with 5FU+LEV had improved overall survival. Conclusions: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset. PMID:21475636

  10. The role of adjuvant in mediating antigen structure and stability.

    Science.gov (United States)

    Braun, Latoya Jones; Eldridge, Aimee M; Cummiskey, Jessica; Arthur, Kelly K; Wuttke, Deborah S

    2012-04-01

    The purpose of this study was to probe the fate of a model antigen, a cysteine-free mutant of bacteriophage T4 lysozyme, to the level of fine structural detail, as a consequence of its interaction with an aluminum (Al)-containing adjuvant. Fluorescence spectroscopy and differential scanning calorimetry were used to compare the thermal stability of the protein in solution versus adsorbed onto an Al-containing adjuvant. Differences in accessible hydrophobic surface areas were investigated using an extrinsic fluorescence probe, 8-Anilino-1-naphthalenesulfonic acid (ANS). As has been observed with other model antigens, the apparent thermal stability of the protein decreased following adsorption onto the adjuvant. ANS spectra suggested that adsorption onto the adjuvant caused an increase in exposure of hydrophobic regions of the protein. Electrostatic interactions drove the adsorption, and disruption of these interactions with high ionic strength buffers facilitated the collection of two-dimensional (15) N heteronuclear single quantum coherence nuclear magnetic resonance data of protein released from the adjuvant. Although the altered stability of the adsorbed protein suggested changes to the protein's structure, the fine structure of the desorbed protein was nearly identical to the protein's structure in the adjuvant-free formulation. Thus, the adjuvant-induced changes to the protein that were responsible for the reduced thermal stability were not observed upon desorption.

  11. Spa adjuvant therapy improves diabetic lower extremity arterial disease.

    Science.gov (United States)

    Qiu, Yongbin; Zhu, Yi; Jia, Wei; Chen, Songhua; Meng, Qingzhou

    2014-08-01

    To investigate the effect of spa adjuvant therapy on diabetic lower extremity arterial disease (LEAD). 128 patients with type II diabetes were separated into three groups according to the degree of lower extremity vascular stenosis. Patients within each group were then randomly divided to receive no treatment (control) or spa adjuvant therapy (treatment). Clinical symptoms, blood pressure and hemodynamic analyses were compared between control and treatment groups by Chi square or t-test. After adjuvant therapy with spa, patients' pain, numbness, and cold sensation were significantly improved compared with control groups (PSpa adjuvant therapy also significantly increased the dorsalis pedis pulse and systolic peak velocity ratio of patients with mild lower extremity vascular stenosis compared with control groups (P0.05). Both in the spa and control groups, there were no significant differences before and after medication for fasting, 2-h postprandial blood glucose and glycosylated hemoglobin (HbA1C) analyses (P>0.05). Spa adjuvant therapy can significantly alleviate lower extremity pain, numbness, and cold sensory symptoms in diabetic LEAD patients with stenosis. Moreover, in LEAD patients with mild stenosis, spa adjuvant therapy also improves the dorsalis pedis pulse and systolic peak velocity ratio, suggesting a potential role for spa therapy as an early intervention strategy to treat the initial stages of disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Activity of glycated chitosan and other adjuvants to PDT vaccines

    Science.gov (United States)

    Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

  13. A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog

    DEFF Research Database (Denmark)

    Christensen, Dennis; Henriksen-Lacey, Malou; Kamath, Arun T;

    2012-01-01

    Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune...

  14. ERM immersion vaccination and adjuvants

    DEFF Research Database (Denmark)

    Skov, J.; Chettri, J. K.; Jaafar, R. M.

    2015-01-01

    Two candidate adjuvants were tested with a commercial ERM dip vaccine (AquaVac™ Relera, MSD Animal Health) for rainbow trout in an experimental design compatible with common vaccination practices at farm level, i.e. immersion of fish in vaccine (±adjuvant) for 30 s. The adjuvants were...... the commercial product Montanide™ IMS 1312 VG PR (SEPPIC), and a soluble and ≥98% pure β-glucan from yeast (Saccharomyces cerevisiae) (Sigma-Aldrich). Hence, five experimental groups in duplicate were established and exposed to vaccine and adjuvants in the following combinations: AquaVac™ Relera (alone); Aqua......Vac™ Relera + Montanide™; AquaVac™ Relera + β-glucan; Montanide™ (alone); and β-glucan (alone). Approximately 450 degree days post-vaccination, the fish were bath-challenged with live Yersinia ruckeri to produce survival curves. Blood, skin and gills were sampled at selected time points during the course...

  15. Adjuvant chemotherapy for advanced endometrial cancer.

    Science.gov (United States)

    Galaal, Khadra; Al Moundhri, Mansour; Bryant, Andrew; Lopes, Alberto D; Lawrie, Theresa A

    2014-05-15

    Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data

  16. Randomized adjuvant study comparing two schemes of 5-fluorouracil and leucovorin in stage B2 and C colon adenocarcinoma: study design and preliminary safety results. Groupe d'Etude et de Recherche Clinique en Oncologie Radiotherapies.

    Science.gov (United States)

    André, T; Colin, P; Louvet, C; Gamelin, E; Bouche, O; Achille, E; Colbert, N; Boaziz, C; Piedbois, P; Tubiana-Mathieu, N; Boutan-Laroze, A; Flesch, M; Billiau, V; Buyse, M; Gramont, A

    2001-02-01

    The aim of this randomized open-label study was to compare a bimonthly with a monthly regimen of 5-fluorouracil (5-FU) and leucovorin for the adjuvant treatment of colon and high-rectum adenocarcinoma. The bimonthly regimen was administered for 2 consecutive days every 14 days as d,L-leucovorin 200 mg/m2 or L-leucovorin 100 mg/m2 as a 2-hour infusion followed by 5-FU bolus of 400 mg/m2 and a 600 mg/m2 5-FU 22-hour continuous infusion (LVSFU2). In the monthly regimen, d,L-leucovorin 200 mg/m2 or L-leucovorin 100 mg/m2 15-minute infusion followed by a 400 mg/m2 15 minute 5-FU bolus was administered for 5 consecutive days every 28 days (FUFOL). Nine hundred five patients with recently resected stage B2 or C colon or high-rectum adenocarcinoma (inferior pole of the tumor subperitoneal) were recruited into the study. Patients were randomized in a 2 x 2 factorial design to receive either LV5FU2 or FUFOL for 24 or 36 weeks. Characteristics of the patients in the two different treatment groups were similar at baseline. Compliance was good. Mean 5-FU dose intensities were 930 mg/ m2/wk and 463 mg/m2/wk for LVSFU2 and FUFOL, respectively. The incidence of maximal grade III-IV toxicities for LVSFU2 and FUFOL was neutropenia 6% and 16% (P < .001), diarrhea 4% and 10% (P < .001), and mucositis 2% and 7% (P < .001), respectively. Maximum grade III-IV toxicities in the LV5FU2 treatment group were significantly lower than in the FUFOL group (10% v 26%; P < .001). Although patients in the LV5FU2 group received twice the dose of 5-FU compared with those in the FUFOL group, LV5FU2 was shown to be less toxic. Efficacy data will be available in 2001.

  17. How to define green adjuvants.

    Science.gov (United States)

    Beck, Bert; Steurbaut, Walter; Spanoghe, Pieter

    2012-08-01

    The concept 'green adjuvants' is difficult to define. This paper formulates an answer based on two approaches. Starting from the Organisation for Economic Cooperation and Development (OECD) definition for green chemistry, production-based and environmental-impact-based definitions for green adjuvants are proposed. According to the production-based approach, adjuvants are defined as green if they are manufactured using renewable raw materials as much as possible while making efficient use of energy, preferably renewable energy. According to the environmental impact approach, adjuvants are defined as green (1) if they have a low human and environmental impact, (2) if they do not increase active ingredient environmental mobility and/or toxicity to humans and non-target organisms, (3) if they do not increase the exposure to these active substances and (4) if they lower the impact of formulated pesticides by enhancing the performance of active ingredients, thus potentially lowering the required dosage of active ingredients. Based on both approaches, a tentative definition for 'green adjuvants' is given, and future research and legislation directions are set out.

  18. Development of a minimal saponin vaccine adjuvant based on QS-21

    Science.gov (United States)

    Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Pillarsetty, Nagavarakishore; Gardner, Jeffrey R.; Livingston, Philip O.; Ragupathi, Govind; Lewis, Jason S.; Tan, Derek S.; Gin, David Y.

    2014-07-01

    Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability and an enigmatic molecular mechanism of action. Herein we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the entire branched trisaccharide domain of QS-21 is dispensable for adjuvant activity and that the C4-aldehyde substituent, previously proposed to bind covalently to an unknown cellular target, is also not required. Biodistribution studies revealed that active adjuvants were retained preferentially at the injection site and the nearest draining lymph nodes compared with the attenuated variants. Overall, these studies have yielded critical insights into saponin structure-function relationships, provided practical synthetic access to non-toxic adjuvants, and established a platform for detailed mechanistic studies.

  19. Designing CAF-adjuvanted dry powder vaccines: Spray drying preserves the adjuvant activity of CAF01

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis

    2013-01-01

    spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol......Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties...... remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6′-dibehenate (TDB) via...

  20. Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo cancer de recto 3 study.

    Science.gov (United States)

    Fernández-Martos, Carlos; Pericay, Carles; Aparicio, Jorge; Salud, Antonieta; Safont, Mariajose; Massuti, Bertomeu; Vera, Ruth; Escudero, Pilar; Maurel, Joan; Marcuello, Eugenio; Mengual, Jose Luis; Saigi, Eugenio; Estevan, Rafael; Mira, Moises; Polo, Sonia; Hernandez, Ana; Gallen, Manuel; Arias, Fernando; Serra, Javier; Alonso, Vicente

    2010-02-10

    PURPOSE The optimal therapeutic sequence of the adjuvant chemotherapy component of preoperative chemoradiotherapy (CRT) for patients with locally advanced rectal cancer is controversial. Induction chemotherapy before preoperative CRT may be associated with better efficacy and compliance. PATIENTS AND METHODS A total of 108 patients with locally advanced rectal cancer were randomly assigned to arm A-preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-induction CAPOX followed by CRT and surgery. The primary end point was pathologic complete response rate (pCR). Results On an intention-to-treat basis, the pCR for arms A and B were 13.5% (95% CI, 5.6% to 25.8%) and 14.3% (95% CI, 6.4% to 26.2%), respectively. There were no statistically significant differences in other end points, including downstaging, tumor regression, and R0 resection. Overall, chemotherapy treatment exposure was higher in arm B than in arm A for both oxaliplatin (P < .0001) and capecitabine (P < .0001). During CRT, grades 3 to 4 adverse events were similar in both arms but were significantly higher in arm A during postoperative adjuvant CT than with induction CT in arm B. There were three deaths in each arm during the treatment period. CONCLUSION Compared with postoperative adjuvant CAPOX, induction CAPOX before CRT had similar pCR and complete resection rates. It did achieve more favorable compliance and toxicity profiles. On the basis of these findings, a phase III study to definitively test the induction strategy is warranted.

  1. Improved survival with early adjuvant chemotherapy after colonic resection for stage III colonic cancer

    DEFF Research Database (Denmark)

    Klein, Mads; Azaquoun, Najah; Jensen, Benny Vittrup

    2015-01-01

    BACKGROUND AND OBJECTIVES: In stage III colonic cancer, time from surgery to start of adjuvant chemotherapy may influence survival. In this study, we evaluated the effect of timing of adjuvant therapy on survival. METHODS: Database study from the Danish Colorectal Cancer Group's national database....... RESULTS: The final population included 1,827 patients scheduled for adjuvant chemotherapy. Adjuvant therapy started within 4 and 8 weeks improved survival when compared to start later than 8 weeks (HR [95%CI]: 1.7 [1.1-2.6]; P = 0.024 and 1.4 [1.07-1.8]; P = 0.013, respectively), whereas...

  2. Characteristics and prognosis of patients with early-stage endometrial cancer who refuse adjuvant radiotherapy.

    Science.gov (United States)

    Koskas, Martin; Huchon, Cyrille; Amant, Frederic

    2016-06-01

    To investigate the risk factors for refusing adjuvant radiotherapy in patients who have undergone surgery for early-stage endometrial cancer, and to compare their survival rates with patients who have undergone adjuvant radiotherapy. Data from the Surveillance, Epidemiology, and End Results database for patients operated on for histologically-proven early-stage endometrioid endometrial cancer, between 1988 and 2012, were screened. Univariate and multivariate logistic regression analyses tested the associations between refusal of adjuvant radiotherapy and demographic, tumoral, and management characteristics. Overall and cancer-related survival rates were compared between 376 patients who refused adjuvant radiotherapy and 752 patients who received adjuvant radiotherapy, matched for demographics (age, race, year of diagnosis, marital status, region), tumoral (grade, FIGO stage, size), and management (lymphadenectomy performed) criteria. 434 of the 16,014 patients (2.7%) who were proposed adjuvant radiotherapy refused this treatment. Older, widowed, divorced, or separated patients, who were recently diagnosed and managed in the Northern plains or Pacific coast (USA), with limited tumoral extension, were more likely to refuse adjuvant radiotherapy. Five-year cancer-related survival was significantly lower in patients who refused adjuvant radiotherapy (88.9% vs. 95.7%, pradiotherapy. Refusing adjuvant radiotherapy increased cancer-related death but probably does not reduce overall survival. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Chemokines as Cancer Vaccine Adjuvants

    Directory of Open Access Journals (Sweden)

    Agne Petrosiute

    2013-10-01

    Full Text Available We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.

  4. New horizons in adjuvants for vaccine development.

    Science.gov (United States)

    Reed, Steven G; Bertholet, Sylvie; Coler, Rhea N; Friede, Martin

    2009-01-01

    Over the last decade, there has been a flurry of research on adjuvants for vaccines, and several novel adjuvants are now in licensed products or in late stage clinical development. The success of adjuvants in enhancing the immune response to recombinant antigens has led many researchers to re-focus their vaccine development programs. Successful vaccine development requires knowing which adjuvants to use and knowing how to formulate adjuvants and antigens to achieve stable, safe and immunogenic vaccines. For the majority of vaccine researchers this information is not readily available, nor is access to well-characterized adjuvants. In this review, we outline the current state of adjuvant research and development and how formulation parameters can influence the effectiveness of adjuvants.

  5. A Review and Prospect on Herbicide Adjuvants

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The history, present status and future prospects of adjuvants application in herbicides were briefly reviewed. Adjuvants can be separated into two groups, activator adjuvants and utility adjuvants. The former directly enhances the efficacy of a herbicide through increasement of herbicide absorption, spreading, cuticular penetration, rainfastness and retention enhancement, and photodegradation of the herbicide can also be decreased. And the latter is utilized for improving application characteristics, behaviors and physical properties of herbicides and reducing or minimizing unwanted side effects on application.

  6. Adjuvants and immunostimulants in fish vaccines: current knowledge and future perspectives.

    Science.gov (United States)

    Tafalla, Carolina; Bøgwald, Jarl; Dalmo, Roy A

    2013-12-01

    Vaccination is the most adequate method to control infectious diseases that threaten the aquaculture industry worldwide. Unfortunately, vaccines are usually not able to confer protection on their own; especially those vaccines based on recombinant antigens or inactivated pathogens. Therefore, the use of adjuvants or immunostimulants is often necessary to increase the vaccine efficacy. Traditional adjuvants such as mineral oils are routinely used in different commercial bacterial vaccines available for fish; however, important side effects may occur with this type of adjuvants. A search for alternative molecules or certain combinations of them as adjuvants is desirable in order to increase animal welfare without reducing protection levels. Especially, combinations that may target specific cell responses and thus a specific pathogen, with no or minor side effects, should be explored. Despite this, the oil adjuvants currently used are quite friendlier with respect to side effects compared with the oil adjuvants previously used. The great lack of fish antiviral vaccines also evidences the importance of identifying optimal combinations of a vaccination strategy with the use of a targeting adjuvant, especially for the promising fish antiviral DNA vaccines. In this review, we summarise previous studies performed with both traditional adjuvants as well as the most promising new generation adjuvants such as ligands for Toll receptors or different cytokines, focussing mostly on their protective efficacies, and also on what is known concerning their effects on the fish immune system when delivered in vivo.

  7. Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Agbahiwe, Harold C.; Wharam, Moody [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Batra, Sachin [Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Cohen, Kenneth [Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Terezakis, Stephanie A., E-mail: sterezak@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2013-02-01

    Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves and descriptive statistics were used for analysis. Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.

  8. High-risk endometrial cancer may be benefit from adjuvant radiotherapy plus chemotherapy.

    Science.gov (United States)

    Miao, Jin-Wei; Deng, Xiao-Hong

    2012-12-01

    To present patterns of practice and outcomes in the adjuvant treatment of intermediate- and high-risk endometrial cancer. Retrospective data on 224 women with intermediate-risk and high-risk endometrial cancer from 1999 to 2006 were reviewed. All patients underwent surgical staging. Patterns of adjuvant treatment, consisting of pelvic radiotherapy, chemotherapy, and radiotherapy plus chemotherapy, were assessed. The 3- and 5-year disease-specific survival (DSS) rates were calculated using the Kaplan-Meier method. The difference in 5-year DSS rate was statistically significant between adjuvant group and non-adjuvant group (80.65% vs. 63.80%, P=0.040). In 110 high-risk patients who underwent adjuvant treatment, both 5-year DSS rate and recurrent rate were significantly different in combined radiotherapy and chemotherapy group compared with radiotherapy alone and chemotherapy alone groups (DSS rate, P=0.049; recurrent rate, P=0.047). In 83 intermediate-risk women who underwent adjuvant treatment, there was no significant difference in 5-year DSS rate and recurrence rate among the combined radiotherapy and chemotherapy, radiotherapy alone and chemotherapy alone groups (DSS rate, P=0.776; recurrent rate, P=0.937). Adjuvant radiotherapy plus chemotherapy is associated with a higher 5-year DSS rate and lower recurrence rate compared with radiotherapy alone and chemotherapy alone in high-risk endometrial cancer patients. Patients with intermediate-risk endometrial cancer may be not likely to benefit from adjuvant combined radiotherapy and chemotherapy.

  9. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  10. Utilization and impact of adjuvant therapy in anaplastic oligodendroglioma: an analysis on 1692 patients.

    Science.gov (United States)

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    The aim of this study was to determine the utilization rates and impact of adjuvant therapy on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1692 patients with AO who underwent surgery were identified. 945 (55.9 %) received adjuvant radiotherapy with concomitant chemotherapy (chemoRT), 102 (6.0 %) adjuvant radiotherapy (RT) sequentially followed by chemotherapy, 244 (14.4 %) adjuvant RT alone, and 401 (23.7 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 vs. 2004-2008 (p 70 vs. <70 (p = 0.018), had private insurance vs. Medicaid vs. no insurance (p < 0.001), or had median income ≥$63,000 vs. <$63,000 (p = 0.014). Those who received adjuvant chemoRT (concomitant or sequential) had significantly better 5-year OS than those who received adjuvant RT alone or no adjuvant therapy (59.8 % vs. 65.0 % vs. 44.9 % vs. 45.6 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age. There was no difference in OS when comparing concomitant chemoRT to sequential RT and chemotherapy (p = 0.481). On multivariate analysis, receipt of adjuvant chemoRT (concomitant or sequential) remained an independent prognostic factor for improved OS. Adjuvant chemoRT (concomitant or sequential) is an independent prognostic factor for improved OS in anaplastic oligodendroglioma and should be considered for all clinically suitable patients who have undergone surgery for the disease.

  11. Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens.

    Science.gov (United States)

    Knudsen, Niels Peter H; Olsen, Anja; Buonsanti, Cecilia; Follmann, Frank; Zhang, Yuan; Coler, Rhea N; Fox, Christopher B; Meinke, Andreas; D'Oro, Ugo; Casini, Daniele; Bonci, Alessandra; Billeskov, Rolf; De Gregorio, Ennio; Rappuoli, Rino; Harandi, Ali M; Andersen, Peter; Agger, Else Marie

    2016-01-21

    The majority of vaccine candidates in clinical development are highly purified proteins and peptides relying on adjuvants to enhance and/or direct immune responses. Despite the acknowledged need for novel adjuvants, there are still very few adjuvants in licensed human vaccines. A vast number of adjuvants have been tested pre-clinically using different experimental conditions, rendering it impossible to directly compare their activity. We performed a head-to-head comparison of five different adjuvants Alum, MF59®, GLA-SE, IC31® and CAF01 in mice and combined these with antigens from M. tuberculosis, influenza, and chlamydia to test immune-profiles and efficacy in infection models using standardized protocols. Regardless of antigen, each adjuvant had a unique immunological signature suggesting that the adjuvants have potential for different disease targets. Alum increased antibody titers; MF59® induced strong antibody and IL-5 responses; GLA-SE induced antibodies and Th1; CAF01 showed a mixed Th1/Th17 profile and IC31® induced strong Th1 responses. MF59® and GLA-SE were strong inducers of influenza HI titers while CAF01, GLA-SE and IC31® enhanced protection to TB and chlamydia. Importantly, this is the first extensive attempt to categorize clinical-grade adjuvants based on their immune profiles and protective efficacy to inform a rational development of next generation vaccines for human use.

  12. The importance of adjuvant formulation in the development of a TB vaccine

    Science.gov (United States)

    Baldwin, Susan L.; Bertholet, Sylvie; Reese, Valerie A.; Ching, Lance K.; Reed, Steven G.; Coler, Rhea N.

    2011-01-01

    An effective protein based vaccine for tuberculosis (TB) will require a safe and effective adjuvant. There are few adjuvants in approved human vaccines, including Alum and the oil-in-water (o/w) based emulsions MF59 (Novartis Vaccines and Diagnostics), AS03 and AS04 (GlaxoSmith Kline Biologics, GSK) AF03 (Sanofi), and liposomes (Crucell). When used with pure, defined proteins, both Alum and emulsion adjuvants are effective at inducing primarily humoral responses. One of the newest adjuvants in approved products is AS04, which combines monophosphoryl lipid A (MPL), a TLR-4 agonist, with Alum. In this study, we compared two adjuvants, an o/w emulsion (SE), and an o/w emulsion incorporating glucopyranosyl lipid adjuvant (GLA), a synthetic TLR-4 agonist, together with a recombinant protein, ID93. Both the emulsion SE and GLA-SE adjuvants induce potent cellular responses in combination with ID93 in mice. ID93/SE induced Th2 biased immune responses, whereas ID93/GLA-SE induced multifunctional CD4+ Th1 cell responses (IFN-γ, TNF-α and IL-2). The ID93/GLA-SE vaccine candidate induced significant protection in mice and guinea pigs, whereas no protection was observed with ID93/SE, as assessed by reductions in bacterial burden, survival, and pathology. These results highlight the importance of properly formulating subunit vaccines with effective adjuvants for use against TB. PMID:22291184

  13. The importance of adjuvant formulation in the development of a tuberculosis vaccine.

    Science.gov (United States)

    Baldwin, Susan L; Bertholet, Sylvie; Reese, Valerie A; Ching, Lance K; Reed, Steven G; Coler, Rhea N

    2012-03-01

    An effective protein-based vaccine for tuberculosis will require a safe and effective adjuvant. There are few adjuvants in approved human vaccines, including alum and the oil-in-water-based emulsions MF59 (Novartis Vaccines and Diagnostics), AS03 and AS04 (GlaxoSmithKline Biologics), AF03 (Sanofi), and liposomes (Crucell). When used with pure, defined proteins, both alum and emulsion adjuvants are effective at inducing primarily humoral responses. One of the newest adjuvants in approved products is AS04, which combines monophosphoryl lipid A, a TLR-4 agonist, with alum. In this study, we compared two adjuvants: a stable oil-in-water emulsion (SE) and a stable oil-in-water emulsion incorporating glucopyranosyl lipid adjuvant, a synthetic TLR-4 agonist (GLA-SE), each together with a recombinant protein, ID93. Both the emulsion SE and GLA-SE adjuvants induce potent cellular responses in combination with ID93 in mice. ID93/SE induced Th2-biased immune responses, whereas ID93/GLA-SE induced multifunctional CD4(+) Th1 cell responses (IFN-γ, TNF-α, and IL-2). The ID93/GLA-SE vaccine candidate induced significant protection in mice and guinea pigs, whereas no protection was observed with ID93/SE, as assessed by reductions in bacterial burden, survival, and pathology. These results highlight the importance of properly formulating subunit vaccines with effective adjuvants for use against tuberculosis.

  14. Adjuvant chemotherapy compliance is not superior after thoracoscopic lobectomy

    DEFF Research Database (Denmark)

    Licht, Peter B; Schytte, Tine; Jakobsen, Erik

    2014-01-01

    BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single-institution, ......BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single...... histopathology. A clinical oncologist, who was blinded to the surgical approach, reviewed all medical oncology charts for types of adjuvant chemotherapy, reasons for not initiating or stopping treatment, number of cycles delivered, and time interval from surgery to initial chemotherapy. RESULTS: During a 6-year...... adjuvant chemotherapy and 121 (38.7%) completed all four cycles. Ordinal logistic regression revealed that chemotherapy compliance (none, partial, and full chemotherapy) was significantly reduced by the patient's age (p

  15. Efficacy and safety of oxaliplatin chemotherapy programs as adjuvant treatment in colorectal cancer after surgery

    Institute of Scientific and Technical Information of China (English)

    杨莉萍

    2013-01-01

    Objective To compare the efficacy and safety of 5-fluorouracil and calcium folinatc combined with oxaliplatin(FOLFOX) program with capecitabine regimen combined oxaliplatin(XELOX) program as adjuvant chemotherapy in advanced colorectal cancer after surgery.

  16. Designing CAF-adjuvanted dry powder vaccines: spray drying preserves the adjuvant activity of CAF01.

    Science.gov (United States)

    Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis; Larsen, Niels Bent; Hinrichs, Wouter Leonardus Joseph; Andersen, Peter; Rantanen, Jukka; Nielsen, Hanne Mørck; Yang, Mingshi; Foged, Camilla

    2013-05-10

    Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6'-dibehenate (TDB) via spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol. Trehalose and lactose were in the glassy state upon co-spray drying with the liposomes, whereas mannitol appeared crystalline, suggesting that the ability of the stabilizer to form a glassy matrix around the liposomes is one of the prerequisites for stabilization. Systematic studies on the effect of process parameters suggested that a fast drying rate is essential to avoid phase separation and lipid accumulation at the surface of the microparticles during spray drying. Finally, immunization studies in mice with CAF01 in combination with the tuberculosis antigen Ag85B-ESAT6-Rv2660c (H56) demonstrated that spray drying of CAF01 with trehalose under optimal processing conditions resulted in the preservation of the adjuvant activity in vivo. These data demonstrate the importance of liposome stabilization via optimization of formulation and processing conditions in the engineering of dry powder liposome formulations.

  17. Adjuvant

    Directory of Open Access Journals (Sweden)

    Ramadan M. Nafae

    2013-07-01

    Conclusion: Adjunctive 7 day course of low dose hydrocortisone IV in patients with CAP hastens clinical recovery and prevents the development of sepsis-related complications with a significant reduction in the duration of mechanical ventilation, duration of IV antibiotics and length of hospital stay with the improvement in hospital outcome and weaning success from mechanical ventilation.

  18. Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

    Science.gov (United States)

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky; Wille-Jørgensen, Peer; Mocellin, Simone

    2012-03-14

    Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes' C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen. Two authors extracted data and a third author performed an independent search for verification. The main outcome measure was the hazard ratio (HR) between the risk of event between the treatment arm (adjuvant chemotherapy

  19. Novel Adjuvants and Immunomodulators for Veterinary Vaccines

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Fang, Yongxiang; Jungersen, Gregers

    2016-01-01

    Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the va...

  20. House dust extracts contain potent immunological adjuvants

    NARCIS (Netherlands)

    Beukelman, C.J.; Dijk, H. van; Aerts, P.C.; Rademaker, P.M.; Berrens, L.; Willers, J.M.N.

    1987-01-01

    A crude aqueous extract of house dust and two house dust subfractions were tested for adjuvant activity in a sensitivity assay performed in mice. Evidence is presented that house dust contains at least two potent immunological adjuvants. One of these, present in both subfractions, was probably endot

  1. Adjuvants: Classification, Modus Operandi, and Licensing

    Science.gov (United States)

    Apostólico, Juliana de Souza

    2016-01-01

    Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations. PMID:27274998

  2. Vaccine Adjuvants: Putting Innate Immunity to Work

    Science.gov (United States)

    Coffman, Robert L.; Sher, Alan; Seder, Robert A.

    2012-01-01

    Adjuvants enhance immunity to vaccines and experimental antigens by a variety of mechanisms. In the past decade, many receptors and signaling pathways in the innate immune system have been defined and these innate responses strongly influence the adaptive immune response. The focus of this review is to delineate the innate mechanisms by which adjuvants mediate their effects. We highlight how adjuvants can be used to influence the magnitude and alter the quality of the adaptive response in order to provide maximum protection against specific pathogens. Despite the impressive success of currently approved adjuvants for generating immunity to viral and bacterial infections, there remains a need for improved adjuvants that enhance protective antibody responses, especially in populations that respond poorly to current vaccines. However, the larger challenge is to develop vaccines that generate strong T cell immunity with purified or recombinant vaccine antigens. PMID:21029960

  3. Modulation of primary immune response by different vaccine adjuvants

    Directory of Open Access Journals (Sweden)

    Annalisa Ciabattini

    2016-10-01

    Full Text Available Adjuvants contribute to enhancing and shaping the vaccine immune response through different modes of action. Since the primary immune response can influence the overall quality of the response generated, here we investigate early biomarkers of adjuvanticity after primary immunization with four different adjuvants combined with the chimeric tuberculosis vaccine antigen H56. C57BL/6 mice were immunized by the subcutaneous route with different vaccine formulations, and the modulation of primary CD4+ T cell and B cell responses was assessed within draining lymph nodes, blood and spleen, 7 and 12 days after priming. Vaccine formulations containing the liposome system CAF01 or a squalene-based oil-in-water emulsion (o/w Squalene, but not aluminum hydroxide (Alum or CpG ODN 1826, elicited a significant primary antigen-specific CD4+ T cell response compared to antigen alone, 7 days after immunization. The effector function of activated CD4+ T cells was skewed towards a Th1/Th17 response by CAF01, while a Th1/Th2 response was elicited by o/w Squalene. Differentiation of B cells in short-lived plasma cells, and subsequent early H56-specific IgG secretion, was observed in mice immunized with o/w Squalene or CpG adjuvants. Tested adjuvants promoted the germinal centre reaction with different magnitude. These results show that the immunological activity of different adjuvants can be characterized by profiling early immunization biomarkers after primary immunization. These data and this approach could give an important contribution to the rational development of heterologous prime-boost vaccine immunization protocols.

  4. Adjuvants are Key Factors for the Development of Future Vaccines: Lessons from the Finlay Adjuvant Platform

    Science.gov (United States)

    Pérez, Oliver; Romeu, Belkis; Cabrera, Osmir; González, Elizabeth; Batista-Duharte, Alexander; Labrada, Alexis; Pérez, Rocmira; Reyes, Laura M.; Ramírez, Wendy; Sifontes, Sergio; Fernández, Nelson; Lastre, Miriam

    2013-01-01

    The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs), AFPL (proteoliposome), and AFCo (cochleate), were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed. PMID:24348475

  5. Survival after adjuvant chemoradiotherapy or surgery alone in resectable adenocarcinoma at the gastro-esophageal junction

    DEFF Research Database (Denmark)

    Kofoed, Steen Christian; Muhic, A; Jensen, Lene Bæksgaard;

    2012-01-01

    Longterm survival after curative resection for adenocarcinoma at the gastro-esophageal junction (GEJ) range between 18% and 50%. In the pivotal Intergroup-0116 Phase III trial by Macdonald et all, adjuvant chemoradiotherapy improved both disease-free and overall survival in curatively resected...... patients with mainly gastric adenocarcinoma. We compared survival data for curatively resected patients with adeno-carcinoma solely at the gastro-esophageal junction (GEJ), treated with surgery alone or surgery and adjuvant chemoradio-therapy....

  6. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA)

    DEFF Research Database (Denmark)

    Goldhirsch, Aron; Gelber, Richard D; Piccart-Gebhart, Martine J

    2013-01-01

    Trastuzumab has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. The standard of care is 1 year of adjuvant trastuzumab, but the optimum duration of treatment is unknown. We compared 2 years of treatment with trastuzumab with 1 year of treatmen......, and updated the comparison of 1 year of trastuzumab versus observation at a median follow-up of 8 years, for patients enrolled in the HERceptin Adjuvant (HERA) trial....

  7. Adjuvant properties of a simplified C32 monomycolyl glycerol analogue.

    Science.gov (United States)

    Bhowruth, Veemal; Minnikin, David E; Agger, Else Marie; Andersen, Peter; Bramwell, Vincent W; Perrie, Yvonne; Besra, Gurdyal S

    2009-04-01

    A simplified C(32) monomycolyl glycerol (MMG) analogue demonstrated enhanced immunostimulatory activity in a dioctadecyl ammonium bromide (DDA)/Ag85B-ESAT-6 formulation. Elevated levels of IFN-gamma and IL-6 were produced in spleen cells from mice immunised with a C(32) MMG analogue comparable activity to the potent Th1 adjuvant, trehalose 6,6'-di-behenate (TDB).

  8. Safety of vaccine adjuvants: focus on autoimmunity.

    Science.gov (United States)

    van der Laan, Jan Willem; Gould, Sarah; Tanir, Jennifer Y

    2015-03-24

    Questions have been recently raised regarding the safety of vaccine adjuvants, particularly in relation to autoimmunity or autoimmune disease(s)/disorder(s) (AID). The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) formed a scientific committee and convened a 2-day workshop, consisting of technical experts from around the world representing academia, government regulatory agencies, and industry, to investigate and openly discuss the issues around adjuvant safety in vaccines. The types of adjuvants considered included oil-in-water emulsions and toll-like receptor (TLR) agonists. The state of science around the use of animal models and biomarkers for the evaluation and prediction of AID were also discussed. Following extensive literature reviews by the HESI committee, and presentations by experts at the workshop, several key points were identified, including the value of animal models used to study autoimmunity and AID toward studying novel vaccine adjuvants; whether there is scientific evidence indicating an intrinsic risk of autoimmunity and AID with adjuvants, or a higher risk resulting from the mechanism of action; and if there is compelling clinical data linking adjuvants and AID. The tripartite group of experts concluded that there is no compelling evidence supporting the association of vaccine adjuvants with autoimmunity signals. Additionally, it is recommended that future research on the potential effects of vaccine adjuvants on AID should consider carefully the experimental design in animal models particularly if they are to be used in any risk assessment, as an improper design and model could result in misleading information. Finally, studies on the mechanistic aspects and potential biomarkers related to adjuvants and autoimmunity phenomena could be developed.

  9. Glucocorticosteroids: as Adjuvant Therapy for Bacterial Infections

    Directory of Open Access Journals (Sweden)

    WONDIM MELKAM

    2015-01-01

    Full Text Available Glucocorticoids (GCs, synthetic analogues of the natural steroid hormones, are well known for their antiinflammatory and immunosuppressive properties in the periphery. They are widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, and transplant rejection. Nowadays, GCs are claimed to have a beneficial role being as adjunct therapy in various infections. Different studies have been conducted to investigate their use as adjuvant therapy for different bacterial infection. This review, therefore, summarizes various bacterial infections for which glucocorticoids are reported to be used as adjuvant therapy, strategies for administration of glucocorticoids, and challenges of using glucocorticoids as adjuvant therapy.

  10. Adjuvant chemotherapy for completely resected non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Toyooka,Shinichi

    2009-10-01

    Full Text Available For many years, surgery alone was the standard treatment for patients with stage I-IIIA non-small-cell lung cancer (NSCLC. However, recent studies have demonstrated that adjuvant chemotherapy provides a survival benefit. The first adjuvant chemotherapy for NSCLC was performed in the 1960s using a key drug known as cyclophosphamide. In the 1980s and early 1990s, a new anti-cancer drug, cisplatin, was developed. The first meta-analysis of this drug was conducted by the Non-small Cell Lung Cancer Collaborative Group in 1995. This analysis comparing surgery with surgery plus chemotherapy containing cisplatin produced a hazard ratio of 0.87 and suggested an absolute benefit of chemotherapy of 5% at 5 years;this difference was not statistically significant (p0.08. Several clinical trials of adjuvant chemotherapy were planned after the meta-analysis conducted in 1995, but the efficacy of adjuvant chemotherapy remained a matter of controversy. However, useful evidence was reported after 2003. The International Adjuvant Lung Cancer Collaborative Group Trial (IALT demonstrated a 4.1% improvement in survival for patients with stage I to III NSCLC. The JBR. 10 trial demonstrated a 15% improvement in 5-year survival for the adjuvant chemotherapy arm in stage IB or II (excluding T3N0 patients. The Adjuvant Navelbine International Trialist Association (ANITA trial reported that the overall survival at 5 years improved by 8.6% in the chemotherapy arm and that this survival rate was maintained at 7 years (8.4% in stage II and IIIA patients. A meta-analysis based on collected and pooled individual patient data from the 5 largest randomized trials was conducted by the Lung Adjuvant Cisplatin Evaluation (LACE. This analysis demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with stage II or III cancer. Alterna-tively, uracil-tegafur has been developed and tested in Japan. The Japan Lung Cancer Research Group (JLCRG on Postsurgical

  11. Intravenous or oral administration of vinorelbine in adjuvant chemotherapy with cisplatin and vinorelbine for resected NSCLC

    DEFF Research Database (Denmark)

    Sorensen, Steffen Filskov; Carus, Andreas; Meldgaard, Peter

    2015-01-01

    OBJECTIVES: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early-stage NSCLC. Vinorelbine can also be administered orally. However, the efficacy of orally administrated vinorelbine in adjuvant treatment of NSCLC is unknown. We...... assessed the overall survival (OS) and disease-free survival (DFS) of patients treated with adjuvant i.v. vinorelbine or p.o. vinorelbine, in combination with i.v. cisplatin. MATERIALS AND METHODS: We reviewed two time-separated cohorts of patients referred to the Department of Oncology at Aarhus...... University Hospital (Denmark) from 2005 to 2012 for adjuvant chemotherapy after surgery for NSCLC. RESULTS AND CONCLUSION: Of the 265 patients included in this study, 126 patients received i.v. and 139 received p.o. vinorelbine/cisplatin. The two groups were comparable with respect to important baseline...

  12. [Adjuvant dermato-cosmetic acne therapy].

    Science.gov (United States)

    Bayerl, Christiane; Degitz, Klaus; Meigel, Eva; Kerscher, Martina

    2010-03-01

    Adjuvant dermato-cosmetic therapy in acne is an essential part of the concept of treating acne after initiation and during maintenance therapy. Those are mechanical peeling, chemical peeling and its combination. It needs supervision by an experienced dermatologist.

  13. High-risk endometrial cancer may be benefit from adjuvant radiotherapy plus chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Jin-Wei Miao; Xiao-Hong Deng

    2012-01-01

    Objective:To present patterns of practice and outcomes in the adjuvant treatment of intermediate-and high-risk endometrial cancer.Methods:Retrospective data on 224 women with intermediate-risk and high-risk endometrial cancer from 1999 to 2006 were reviewed.All patients underwent surgical staging.Patterns of adjuvant treatment,consisting of pelvic radiotherapy,chemotherapy,and radiotherapy plus chemotherapy,were assessed.The 3-and 5-year disease-specific survival (DSS) rates were calculated using the Kaplan-Meier method.Results:The difference in 5-year DSS rate was statistically significant between adjuvant group and non-adjuvant group (80.65% vs.63.80%,P=0.040).In 110 high-risk patients who underwent adjuvant treatment,both 5-year DSS rate and recurrent rate were significantly different in combined radiotherapy and chemotherapy group compared with radiotherapy alone and chemotherapy alone groups (DSS rate,P=0.049; recurrent rate,P=0.047).In 83 intermediate-risk women who underwent adjuvant treatment,there was no significant difference in 5-year DSS rate and recurrence rate among the combined radiotherapy and chemotherapy,radiotherapy alone and chemotherapy alone groups (DSS rate,P=0.776; recurrent rate,P=0.937).Conclusions:Adjuvant radiotherapy plus chemotherapy is associated with a higher 5-year DSS rate and lower recurrence rate compared with radiotherapy alone and chemotherapy alone in high-risk endometrial cancer patients.Patients with intermediate-risk endometrial cancer may be not likely to benefit from adjuvant combined radiotherapy and chemotherapy.

  14. Adjuvants for spraying of fungicides in wheat

    OpenAIRE

    2014-01-01

    The foliar diseases and spike can markedly reduce the yield of wheat. Despite prevailing chemical control in the management of disease, studies with adjuvants to improve the performance of fungicides are still incipient. The aim of this study was to evaluate the effect of adding adjuvants to chemical fungicides to control leaf diseases and spike, as well as on the yield of wheat crop. The experimental design was a randomized block design with 05 treatments: control (no fungicide application i...

  15. Tocotrienols are good adjuvants for developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Ammu

    2010-01-01

    Full Text Available Abstract Background Dendritic cells (DCs have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. Methods In this study we have used tocotrienol-rich fraction (TRF, a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF and DC pulsed with tumour lysate from 4T1 cells (DC+TL. Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF while two groups of animal which were supplemented daily with carrier oil (control and with TRF (TRF. After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Results Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8 and natural killer cells (NK were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Conclusion Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.

  16. Applications of nanomaterials as vaccine adjuvants.

    Science.gov (United States)

    Zhu, Motao; Wang, Rongfu; Nie, Guangjun

    2014-01-01

    Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigen-specific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials' physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants.

  17. A Purified Recombinant Lipopeptide as Adjuvant for Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Ying-Chyi Song

    2014-01-01

    Full Text Available Synthetic lipopeptides have been widely used as vaccine adjuvants to enhance immune responses. The present study demonstrated that the tryptic N-terminal fragment of the lipoprotein rlipo-D1E3 (lipo-Nter induces superior antitumor effects compared to a synthetic lipopeptide. The lipo-Nter was purified and formulated with protein or peptide vaccines to determine if lipo-Nter could be used as a novel adjuvant and could induce antitumor immunity in a cervical cancer model. Purified lipo-Nter activated the maturation of bone marrow-derived dendritic cells (BM-DCs, leading to the secretion of TNF-α through TLR2/6 but not TLR1/2. A recombinant mutant HPV16 E7 (rE7m protein was mixed with lipo-Nter to immunize the mice; the anti-E7 antibody titers were increased, and the T helper cells were skewed toward the Th1 fate (increased IL-2 and decreased IL-5 secretion. Single-dose injection of rE7m and lipo-Nter inhibited tumor growth, but the injection of rE7m alone did not. Accordingly, lipo-Nter also enhanced the antitumor immunity of the E7-derived peptide but not the synthetic lipopeptide (Pam3CSK4. We demonstrated that the lipo-Nter of a bacterial-derived recombinant lipoprotein is a novel adjuvant that could be used for the development of a new generation of vaccines.

  18. Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Showalter, Timothy N., E-mail: timothy.showalter@jeffersonhospital.org [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Ohri, Nitin; Teti, Kristopher G. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Foley, Kathleen A. [Strategic Consulting, Thomson Reuters Healthcare, Cambridge, MA (United States); Keith, Scott W. [Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Trabulsi, Edouard J.; Lallas, Costas D. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Dicker, Adam P. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Hoffman-Censits, Jean [Department of Medical Oncology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Pizzi, Laura T. [School of Pharmacy, Thomas Jefferson University, Philadelphia, PA (United States); Gomella, Leonard G. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States)

    2012-02-01

    Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations. Conclusions: U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.

  19. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.

    Science.gov (United States)

    Mold, Matthew; Shardlow, Emma; Exley, Christopher

    2016-08-12

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al(3+) in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

  20. Improved immunogenicity of tetanus toxoid by Brucella abortus S19 LPS adjuvant.

    Science.gov (United States)

    Mohammadi, Mohsen; Kianmehr, Zahra; Kaboudanian Ardestani, Sussan; Gharegozlou, Behnaz

    2014-09-01

    Adjuvants are used to increase the immunogenicity of new generation vaccines, especially those based on recombinant proteins. Despite immunostimulatory properties, the use of bacterial lipopolysaccharide (LPS) as an adjuvant has been hampered due to its toxicity and pyrogenicity. Brucella abortus LPS is less toxic and has no pyrogenic properties compared to LPS from other gram negative bacteria. To evaluate the adjuvant effect of B. abortus (vaccine strain, S19) LPS for tetanus toxoid antigen (TT) and to investigate the protective effect of different tetanus vaccine preparations. LPS was extracted and purified from B. abortus S19 and KDO, glycan, phosphate content, and protein contamination were measured. Adipic acid dihydrazide (ADH) was used as a linker for conjugation of TT to LPS. Different amounts of B. abortus LPS, TT, TT conjugated with LPS, and TT mixed with LPS or complete Freund's adjuvant (CFA) were injected into mice and antibody production against TT was measured. The protective effect of induced antibodies was determined by LD50. Immunization of mice with TT+LPS produced the highest anti-TT antibody titer in comparison to the group immunized with TT without any adjuvant or the groups immunized with TT-LPS or TT+CFA. Tetanus toxid-S19 LPS also produced a 100% protective effect against TT in immunized mice. These data indicate that B. abortus LPS enhances the immune responses to TT and suggest the possible use of B. abortus LPS as an adjuvant in vaccine preparations.

  1. Orthotopic ileal neobladder reconstruction for bladder cancer: is adjuvant chemotherapy safe?

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    Murugesan Manoharan

    2006-10-01

    Full Text Available OBJECTIVE: We examined our database of patients undergoing radical cystectomy (RC with orthotopic neobladder (NB to determine whether adjuvant chemotherapy in this group is safe. MATERIALS AND METHODS: We performed a retrospective analysis of patients who underwent radical cystectomy and urinary diversion between 1992 and 2004. Relevant clinical and therapeutic data were entered into a database. High-risk bladder cancer patients who underwent NB were identified. They were stratified into 2 groups, those who received adjuvant chemotherapy and those who did not. The incidence of complications between the 2 groups was analyzed and compared. RESULTS: Over the 12-year period, 136 patients underwent RC and NB construction for bladder cancer. Of these, 83 patients were at high risk for recurrence. Nineteen patients received adjuvant chemotherapy and 64 did not. The complication rate in the adjuvant chemotherapy group was 53% and it was 23% in those who did not receive chemotherapy. There were no perioperative or treatment related death. There were 2 patients with grade 4 toxicity in the adjuvant chemotherapy group. There was a statistical difference between these two groups with regard to the incidence of complications. However, none of these complications was life-threatening, required only conservative treatment and caused no long-term disability. CONCLUSIONS: Adjuvant chemotherapy is a safe treatment for patients undergoing RC and NB substitution. Hence, the option of orthotopic NB should not be denied in selected bladder cancer patients with high risk for recurrent disease.

  2. Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity

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    Karen A.O. Martins

    2016-01-01

    Full Text Available Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol, MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

  3. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations

    Science.gov (United States)

    Mold, Matthew; Shardlow, Emma; Exley, Christopher

    2016-08-01

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al3+ in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

  4. Adjuvant radiotherapy is not supported in patients with verrucous carcinoma of the oral cavity.

    Science.gov (United States)

    Mohan, Suresh; Pai, Sara I; Bhattacharyya, Neil

    2017-06-01

    To analyze the impact of adjuvant radiation therapy (RT) on overall survival (OS) and disease-specific survival (DSS) in patients with verrucous carcinoma (VC) as compared to squamous cell carcinoma (SCC) of the oral cavity. Cross-sectional population analysis. Cases of nonmetastatic VC/SCC of the oral cavity were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (1988-2013). Kaplan-Meier survivals, stratified according to T stage, were compared between VC and SCC for treatment with or without adjuvant RT. A total of 18,819 VC/SCC cases were identified. There were 581 (3.1%) VC (mean age 69.6 years, 48.9% female) versus 18,238 (97.0%) SCC (mean age, 65.3, 37.1% female) patients. Verrucous carcinoma patients receiving surgery alone (N = 539) demonstrated a trend toward improved OS versus VC patients receiving surgery and RT (N = 40) (117.0 vs. 71.4 months, respectively, P = 0.119). There was a statistically significant improvement in DSS in VC patients receiving surgery alone (217.2 vs. 110.9 months, P = 0.05). Verrucous carcinoma patients treated with adjuvant RT demonstrated a trend toward a worse OS (71.4 vs. 93.0 months, P = 0.992) and DSS (110.9 vs. 162.3 months, P = 0.275) compared to SCC treated with adjuvant RT, suggesting a different biology and radiosensitivity between VC and SCC. Verrucous carcinoma treated with adjuvant RT had a worse OS and DSS compared to both VC treated with surgery alone and SCC treated with surgery and adjuvant RT. Consideration should be given to surgical re-section rather than adjuvant RT in patients with positive margins or local recurrence. 2C. Laryngoscope, 127:1334-1338, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  5. Review: Adjuvant effects of saponins on animal immune responses

    Institute of Scientific and Technical Information of China (English)

    RAJPUT Zahid Iqbal; HU Song-hua; XIAO Chen-wen; ARIJO Abdullah G.

    2007-01-01

    Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines,ISCOMs (immunostimulating complexes), Freund's complete adjuvant, Freund's incomplete adjuvant, alums, bacterial toxins etc.,are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed.

  6. Cost-utility analysis of adjuvant goserelin (Zoladex and adjuvant chemotherapy in premenopausal women with breast cancer

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    Cheng Tsui

    2012-01-01

    Full Text Available Abstract Background Increased health care costs have made it incumbent on health-care facilities and physicians to demonstrate both clinical and cost efficacy when recommending treatments. Though studies have examined the cost-effectiveness of adjuvant goserelin with radiotherapy for locally advanced prostate cancer, few have compared the cost-effectiveness of adjuvant goserelin to adjuvant chemotherapy alone in premenopausal breast cancer. Methods In this retrospective study at one hospital, the records of 152 patients with stage Ia to IIIa ER + breast cancer who received goserelin or chemotherapy were reviewed. Survival analysis was assessed by the Kaplan-Meier method. Patients were interviewed to evaluate their quality of life using the European Organization for Research and Treatment Quality of Life questionnaire (EORTC-QLQ-C30, version 4.0, and to obtain the utility value by the standard gamble (SG and visual scale (VS methods. Total medical cost was assessed from the (National Health Insurance NHI payer's perspective. Results Survival at 11 years was significantly better in the groserelin group (P Conclusions Goserelin therapy results in better survival and higher utility-weighted life-years, and is more cost-effective than TC or TEC chemotherapy.

  7. Gamma ray sterilization of delta inulin adjuvant particles (Advax™) makes minor, partly reversible structural changes without affecting adjuvant activity.

    Science.gov (United States)

    Cooper, P D; Barclay, T G; Ginic-Markovic, M; Petrovsky, N

    2014-01-23

    We earlier identified a developmental series of seven isoforms/polymorphs of microparticulate inulin by comparing non-covalent bonding strengths. Their pharmaceutical utility lies in the modulation of cellular immunity, exploited as vaccine adjuvants (Advax™) especially for delta inulin (DI). As such particles cannot be sterilized by filtration we explore the effect of (60)Co gamma radiation (GR) on inulin isoforms, particularly DI. Its adjuvant activity and overt physical properties were unaffected by normal GR sterilizing doses (up to 25kGy). Heating irradiated isoform suspensions near their critical dissolution temperature revealed increased solubility deduced to reflect a single lethal event in one component of a multi-component structure. Local oxidative effects of GR on DI were not found. The observed DI loss was almost halved by re-annealing at the critical temperature: surviving inulin chains apparently reassemble into smaller amounts of the original type of structure. Colorimetric tetrazolium assay revealed increases in reducing activity after GR of raw inulin powder, which yielded DI with normal physical properties but only 25% normal recovery yet 4× normal reducing ability, implying final retention of some GR-changed inulin chains. These findings suggest minimal inulin chain cleavage and confirm that GR may be a viable strategy for terminal sterilization of microparticulate inulin adjuvants.

  8. Toll-Like Receptor Ligand-Based Vaccine Adjuvants Require Intact MyD88 Signaling in Antigen-Presenting Cells for Germinal Center Formation and Antibody Production

    Science.gov (United States)

    Mosaheb, Munir M.; Reiser, Michael L.; Wetzler, Lee M.

    2017-01-01

    Vaccines are critical in the fight against infectious diseases, and immune-stimulating adjuvants are essential for enhancing vaccine efficacy. However, the precise mechanisms of action of most adjuvants are unknown. There is an urgent need for customized and adjuvant formulated vaccines against immune evading pathogens that remain a risk today. Understanding the specific role of various cell types in adjuvant-induced protective immune responses is vital for an effective vaccine design. We have investigated the role of cell-specific MyD88 signaling in vaccine adjuvant activity in vivo, using Neisserial porin B (PorB), a TLR2 ligand-based adjuvant, compared with an endosomal TLR9 ligand (CpG) and toll-like receptor (TLR)-independent (alum, MF59) adjuvants. We found that intact MyD88 signaling is essential, separately, in all three antigen-presenting cell types [B cells, macrophages, and dendritic cells (DCs)] for optimal TLR ligand-based adjuvant activity. The role of MyD88 signaling in B cell and DC in vaccine adjuvant has been previously investigated. In this study, we now demonstrate that the immune response was also reduced in mice with macrophage-specific MyD88 deletion (Mac-MyD88−/−). We demonstrate that TLR-dependent adjuvants are potent inducers of germinal center (GC) responses, but GCs are nearly absent in Mac-MyD88−/− mice following immunization with TLR-dependent adjuvants PorB or CpG, but not with TLR-independent adjuvants MF59 or alum. Our findings reveal a unique and here-to-for unrecognized importance of intact MyD88 signaling in macrophages, to allow for a robust vaccine-induced immune responses when TLR ligand-based adjuvants are used.

  9. Adjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation.

    Science.gov (United States)

    Seibel, Ira; Riechardt, Aline I; Heufelder, Jens; Cordini, Dino; Joussen, Antonia M

    2017-06-01

    This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures. Retrospective cohort study. All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included. A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95.9% and 94.8% after 5 years, respectively. A total of 110 (4.4%) patients required secondary enucleation. Unresponsive neovascular glaucoma was the leading cause of secondary enucleation in 78 of the 2499 patients (3.1%). The 5-year enucleation-free survival rate was 94.8% in the endoresection group, 94.3% in the endodrainage group, and 93.5% in the comparator group. The log-rank test showed P = .014 (comparator group vs endoresection group) and P = .06 (comparator group vs endodrainage-vitrectomy group). Patients treated with endoresection or endodrainage-vitrectomy developed less radiation retinopathy (30.5% and 37.4% after 5 years, P = .001 and P = .048 [Kaplan-Meier], respectively) and less neovascular glaucoma (11.6% and 21.3% after 5 years, P = .001 and P = .01 [Kaplan-Meier], respectively) compared with the comparator group (52.3% radiation retinopathy and 57.8% neovascular glaucoma after 5 years). This study suggests that in larger tumors the enucleation and neovascular glaucoma rates might be reduced by adjuvant surgical procedures. Although endoresection is the most promising adjuvant treatment option, the endodrainage-vitrectomy is recommended in patients who are ineligible for endoresection. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Long-term results of International Breast Cancer Study Group Trial VIII: adjuvant chemotherapy plus goserelin compared with either therapy alone for premenopausal patients with node-negative breast cancer.

    Science.gov (United States)

    Karlsson, P; Sun, Z; Braun, D; Price, K N; Castiglione-Gertsch, M; Rabaglio, M; Gelber, R D; Crivellari, D; Collins, J; Murray, E; Zaman, K; Colleoni, M; Gusterson, B A; Viale, G; Regan, M M; Coates, A S; Goldhirsch, A

    2011-10-01

    The International Breast Cancer Study Group Trial VIII compared long-term efficacy of endocrine therapy (goserelin), chemotherapy [cyclophosphamide, methotrexate and fluorouracil (CMF)], and chemoendocrine therapy (CMF followed by goserelin) for pre/perimenopausal women with lymph-node-negative breast cancer. From 1990 to 1999, 1063 patients were randomized to receive (i) goserelin for 24 months (n = 346), (ii) six courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or (iii) six courses of CMF plus 18 months goserelin (CMF→ goserelin; n = 357). Tumors were classified as estrogen receptor (ER) negative (19%), ER positive (80%), or ER unknown (1%); 19% of patients were younger than 40. Median follow-up was 12.1 years. For the ER-positive cohort, sequential therapy provided a statistically significant benefit in disease-free survival (DFS) (12-year DFS = 77%) compared with CMF alone (69%) and goserelin alone (68%) (P = 0.04 for each comparison), due largely to the effect in younger patients. Patients with ER-negative tumors whose treatment included CMF had similar DFS (12-year DFS CMF = 67%; 12-year DFS CMF→ goserelin = 69%) compared with goserelin alone (12-year DFS = 61%, P= NS). For pre/perimenopausal women with lymph-node-negative ER-positive breast cancer, CMF followed by goserelin improved DFS in comparison with either modality alone. The improvement was the most pronounced in those aged below 40, suggesting an endocrine effect of prolonged CMF-induced amenorrhea.

  11. Adjuvant radiotherapy for stage I endometrial cancer.

    Science.gov (United States)

    Kong, Anthony; Johnson, Nick; Kitchener, Henry C; Lawrie, Theresa A

    2012-04-18

    This is an updated version of the original Cochrane review published in Issue 2, 2007. The role of radiotherapy (both pelvic external beam radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I endometrial cancer following hysterectomy remains controversial. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end-2005 for the original review, and extended the search to January 2012 for the update. We included randomised controlled trials (RCTs) that compared post-operative adjuvant radiotherapy (either EBRTor VBT, or both) versus no radiotherapy or VBT in women with stage I endometrial cancer. Two review authors independently assessed trials and extracted data to a specifically designed data collection form. The primary outcome was overall survival. Secondary outcomes were endometrial cancer-related deaths, locoregional recurrence and distant recurrence. Meta-analyses were performed using Cochrane Review Manager Software 5.1. We included eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and one trial (645 women) compared VBTwith no additional treatment. We considered six of the eight trials to be of a high quality. Time-to-event data were not available for all trials and all outcomes.EBRT (with or without VBT) compared with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly reduced locoregional recurrence (time-to-event data: five trials, 2965 women; Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to 0.47). This reduced risk of locoregional recurrence did not translate into improved overall survival (time-to-event data: five trials, 2,965 women; HR 0.99, 95% CI 0.82 to1.20; and dichotomous data: seven trials, 3628 women; RR 0.98, 95

  12. (Neo)adjuvant systemic therapy for melanoma.

    Science.gov (United States)

    van Zeijl, M C T; van den Eertwegh, A J; Haanen, J B; Wouters, M W J M

    2017-03-01

    Surgery still is the cornerstone of treatment for patients with stage II and III melanoma, but despite great efforts to gain or preserve locoregional control with excision of the primary tumour, satellites, intransits, sentinel node biopsy and lymphadenectomy, surgery alone does not seem to improve survival any further. Prognosis for patients with high risk melanoma remains poor with 5-year survival rates of 40 to 80%. Only interferon-2b has been approved as adjuvant therapy since 1995, but clinical integration is low considering the high risk-benefit ratio. In recent years systemic targeted- and immunotherapy have proven to be beneficial in advanced melanoma and could be a promising strategy for (neo)adjuvant treatment of patients with resectable high risk melanomas as well. Randomised, placebo- controlled phase III trials on adjuvant systemic targeted- and immunotherapy are currently being performed using new agents like ipilimumab, pembrolizumab, nivolumab, vemurafenib and dabrafenib plus trametinib. In this article we review the literature on currently known adjuvant therapies and currently ongoing trials of (neo)adjuvant therapies in high risk melanomas.

  13. Mycophenolate mofetil as adjuvant in pemphigus vulgaris

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    Sarma Nilendu

    2007-01-01

    Full Text Available Pemphigus vulgaris (PV is a life threatening autoimmune blistering disease of skin and mucous membranes. Advent of systemic steroids has greatly reduced the mortality rate. However, steroids and adjuvant immunosuppressive therapy are nowadays frequent contributory agents of morbidity and mortality of PV. Mycophenolate mofetil (MMF has been reported to be an effective adjuvant to systemic steroids. It helps in increasing the immunosuppressive effect and minimizing the toxicities by steroid sparing effect. However, its efficacy in refractory cases of PV is not well documented. The lowest possible dose with satisfactory therapeutic efficacy and least side effects is known. We used MMF 1 g/day and systemic steroids in 3 Indian patients with pemphigus vulgaris who were resistant to systemic steroid monotherapy or combination treatment with azathioprine. In our experience, MMF offers an effective adjuvant with minimal side-effects in the treatment of resistant PV.

  14. Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

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    Lima Carmen SP

    2011-03-01

    Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

  15. Effects of adjuvant Montanide™ ISA 763 A VG in rainbow trout injection vaccinated against Yersinia ruckeri.

    Science.gov (United States)

    Jaafar, Rzgar M; Chettri, Jiwan K; Dalsgaard, Inger; Al-Jubury, Azmi; Kania, Per W; Skov, Jakob; Buchmann, Kurt

    2015-12-01

    Enteric redmouth disease (ERM) caused by the fish pathogen Yersinia ruckeri is a major threat to freshwater production of rainbow trout (Oncorhynchus mykiss) throughout all life stages. Injection vaccination of rainbow trout against Y. ruckeri infection has been shown to confer better protection compared to the traditionally applied immersion vaccination. It may be hypothesized, based on experience from other vaccines, that adjuvants may increase the protective level of ERM injection vaccines even more. Controlled comparative vaccination studies have been performed to investigate effects of the oil adjuvant Montanide™ ISA 763 A VG (Seppic) when added to an experimental Y. ruckeri bacterin (containing both biotype 1 and 2 of serotype O1). A total of 1000 fish with mean weight 19 g was divided into five different groups (in duplicated tanks 2 × 100 fish per group) 1) non-vaccinated control fish (NonVac), 2) fish injected with a commercial vaccine (AquaVac(®) Relera™) (ComVac), 3) fish injected with an experimental vaccine (ExpVac), 4) fish injected with an experimental vaccine + adjuvant (ExpVacAdj) and 5) fish injected with adjuvant alone (Adj). Injection of the experimental vaccine (both adjuvanted and non-adjuvanted) induced a significantly higher antibody (IgM) level, increased occurrence of IgM(+) cells in spleen tissue and significant up-regulation of several immune genes. Additional experiments using a higher challenge dosage suggested an immune enhancing effect of the adjuvant as the challenge produced 100% mortality in the NonVac group, 60% mortality in both of ComVac and Adj groups and only 13 and 2.5% mortalities in the ExpVac and the ExpVacAdj groups, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Montanide ISA 71 VG is Advantageous to Freund's Adjuvant in Immunization Against S. aureus Infection of Mice.

    Science.gov (United States)

    Klimka, A; Michels, L; Glowalla, E; Tosetti, B; Krönke, M; Krut, O

    2015-05-01

    The enormous capacity of Staphylococcus aureus to acquire antibiotic resistance makes it a permanent task to search for and to develop new anti-infectives. One of the possible approaches is the early active immunization of risk patients and animal stocks to prevent S. aureus infections. Based on a S. aureus proteome screen with S. aureus-specific human antiserum, we have previously identified several anchorless cell wall proteins to be used as novel vaccine candidates. To develop an efficient anti-S. aureus vaccine, the supplemented adjuvants Montanide(™) ISA 71 VG and ISA 206 were compared to Freund's adjuvant in terms of handling, induction of cytokine profile, triggering antigen-specific immunoglobulin production of different IgG subclasses and provision of increased survival rates in our S. aureus sepsis mouse model. Immunization with ISA 71 VG in comparison with Freund's adjuvant induced slightly delayed but comparably strong increase of antigen-specific antibody titres and conferred protective effect against S. aureus challenge. In contrast using ISA 206 as adjuvant, significantly lower IgG titres and consequently, no protective effect against S. aureus infection were observed. Handling and tolerability of the Montanide is superior to Freund's adjuvant. Montanide(™) ISA 71 VG can serve as an effective adjuvant replacement for Freund's adjuvant in research with a prospective usage in animal and human vaccines against bacterial pathogens. © 2015 John Wiley & Sons Ltd.

  17. Microbiota Influences Vaccine and Mucosal Adjuvant Efficacy

    Science.gov (United States)

    2017-01-01

    A symbiotic relationship between humans and the microbiota is critical for the maintenance of our health, including development of the immune system, enhancement of the epithelial barrier, and acquisition of nutrients. Recent research has shown that the microbiota impacts immune cell development and differentiation. These findings suggest that the microbiota may also influence adjuvant and vaccine efficacy. Indeed, several factors such as malnutrition and poor sanitation, which affect gut microbiota composition, impair the efficacy of vaccines. Although there is little evidence that microbiota alters vaccine efficacy, further understanding of human immune system-microbiota interactions may lead to the effective development of adjuvants and vaccines for the treatment of diseases. PMID:28261017

  18. [Adjuvant chemotherapy for patients with rectal cancer].

    Science.gov (United States)

    Qvortrup, Camilla; Mortensen, John Pløen; Pfeiffer, Per

    2013-09-09

    A new Cochrane meta-analysis evaluated adjuvant chemotherapy (5-fluorouracil (5FU)-based, not modern combination chemotherapy) in almost 10,000 patients with rectal cancer and showed a 17% reduction in mortality corresponding well to the efficacy observed in recent studies, which reported a reduction in mortality just about 20%. The authors recommend adjuvant chemotherapy which is in accordance with the Danish national guidelines where 5-FU-based chemotherapy is recommended for stage III and high-risk stage II rectal cancer.

  19. Adjuvants and vector systems for allergy vaccines.

    Science.gov (United States)

    Moingeon, Philippe; Lombardi, Vincent; Saint-Lu, Nathalie; Tourdot, Sophie; Bodo, Véronique; Mascarell, Laurent

    2011-05-01

    Allergen-specific immunotherapy represents a curative treatment of type I allergies. Subcutaneous immunotherapy is conducted with allergens adsorbed on aluminum hydroxide or calcium phosphate particles, whereas sublingual immunotherapy relies on high doses of soluble allergen without any immunopotentiator. There is a potential benefit of adjuvants enhancing regulatory and Th1 CD4+T cell responses during specific immunotherapy. Molecules affecting dendritic cells favor the induction of T regulatory cell and Th1 responses and represent valid candidate adjuvants for allergy vaccines. Furthermore, the interest in viruslike particles and mucoadhesive particulate vector systems, which may better address the allergen(s) to tolerogenic antigen-presenting cells, is documented.

  20. Adjuvanted rush immunotherapy using CpG oligodeoxynucleotides in experimental feline allergic asthma.

    Science.gov (United States)

    Reinero, Carol R; Cohn, Leah A; Delgado, Cherlene; Spinka, Christine M; Schooley, Elizabeth K; DeClue, Amy E

    2008-02-15

    Allergic asthma is driven by relative overexpression of Th2 cell-derived cytokines in response to aeroallergens. In independent studies, both allergen-specific rush immunotherapy (RIT) and CpG oligodeoxynucleotides (ODN) showed promise in blunting eosinophilic inflammation in a model of feline allergic asthma. We hypothesized that RIT using allergen and CpG ODN would work synergistically to dampen the asthmatic phenotype in experimentally asthmatic cats. Twelve cats with asthma induced using Bermuda grass allergen (BGA) were studied. Of these, six were administered adjuvanted BGA RIT using CpG ODN #2142; six were administered placebo (saline) RIT and later crossed over to adjuvanted RIT. Over 2 days, subcutaneous CpG ODN (0.5ng/kg) with BGA (increasing doses every 2h from 20 to 200microg) was administered. Adverse events were recorded and compared with historical controls. Percentage of eosinophils in bronchoalveolar lavage fluid (BALF), % peripheral CD4+CD25+ T regulatory cells (Tregs), lymphocyte proliferation in response to ConA, and cytokine concentrations in BALF were measured over 2 months. Group mean BALF % eosinophils for the adjuvanted RIT cats were significantly lower at week 1 and month 1 (p=0.03 for both), and marginally significantly lower at month 2 (p=0.09) compared with placebo RIT cats. By the end of the study, 8/12 treated cats had BALF % eosinophils within the reference range for healthy cats. Adjuvanted RIT, but not placebo RIT, cats had significant decreases in the ConA stimulation index over time (p=0.05). BALF IL-4 concentrations were significantly higher at week 1 in adjuvanted RIT cats compared with baseline and month 2, and also with placebo RIT cats at week 1. No significant differences were detected between treatments or over time for IL-10 or IFN-gamma concentrations in BALF or for %Tregs cells in peripheral blood. Adjuvanted RIT using CpG ODN in experimental feline asthma dampens eosinophilic airway inflammation. Adverse effects

  1. Capecitabine with radiation is an effective adjuvant therapy in gastric cancers

    Institute of Scientific and Technical Information of China (English)

    Chee; Kian; Tham; Su; Pin; Choo; Donald; Yew; Hee; Poon; Han; Chong; Toh; Simon; Yew; Kuang; Ong; Sze; Huey; Tan; Michael; Lian; Chek; Wang; Kian; Fong; Foo

    2010-01-01

    AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers.METHODS:All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed.Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT o...

  2. Gastric carcinoma: curative resection and adjuvant chemotherapy.

    Science.gov (United States)

    Carrillo Hernández, J F; Ernesto de Obaldía Castillo, G; Ramírez Ortega, C; Frías Mendivil, M; Pardo, M

    1994-01-01

    A retrospective study of gastric adenocarcinoma treated with surgery as curative attempt was performed at the Oncology Service, in the Hospital Regional 20 de Noviembre, ISSSTE. Morbidity and mortality of the surgical procedures were evaluated, the significance of several risk factors and the survival impact of adjuvant chemotherapy with 5-fluorouracil (5-FU) and mitomycin C (MMC). In the period from 1975 to 1991 a total of 483 new cases were seen. In only 54 patients (11.2%) was it possible to undertake a curative resection. The patients were assigned to three groups of treatment: surgery alone (14 cases), surgery + 5-FU (19 cases), and surgery + 5-FU+MMC (21 cases). Three different types of surgical techniques are regularly performed in our service for gastric cancer treatment: Billroth II distal gastrectomy, total gastrectomy with Roux-En-Y reconstruction, and esophagogastrectomy with esophagogastrostomy. Surgical morbidity and mortality was low, with 9% of duodenal stump fistulas and 27% with partial stenosis of esophagojejunostomy; the operative mortality was zero. Chemotherapy toxicity was transient and low, no related deaths were recorded. The prognostic factors associated significantly with survival were lymph node status and tumor penetration. The histologic differentiation as well as the tumor location and type of surgery had no significance. The estimated 5-year survival of the patients treated with surgery alone was 62%, while that of the patients treated with surgery plus chemotherapy was 38%. These groups were not comparable, however, because of important differences in their prognostic factors. The groups treated with 5-FU alone or in combination with MMC had no survival difference between them.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Soluble proteins modified with acetaldehyde and malondialdehyde are immunogenic in the absence of adjuvant.

    Science.gov (United States)

    Thiele, G M; Tuma, D J; Willis, M S; Miller, J A; McDonald, T L; Sorrell, M F; Klassen, L W

    1998-11-01

    Recent studies have shown that the alcohol metabolites malondialdehyde and acetaldehyde can combine to form a stable adduct (MAA) on proteins. This adduct has been detected in the livers of rats chronically consuming ethanol, and serum antibodies to MAA have been observed at significantly higher concentrations in ethanol-fed when compared with pair-fed or chow-fed control rats. More recently, preliminary studies have strongly suggested that the MAA adduct is capable of stimulating antibody responses to soluble proteins in the absence of adjuvants. The antibodies produced recognize either the MAA epitope or the carrier protein itself. Therefore, it was the purpose of this study to examine the potential immunogenicity of MAA-modified exogenous proteins in the absence of adjuvants. Balb/c mice were immunized in the presence or absence of adjuvant with different concentrations of unmodified or MAA-modified proteins. The antibody response to both the MAA epitope and unmodified protein epitopes were determined by ELISA. In the absence of adjuvant, significant antibody responses were induced to both the MAA epitope and nonmodified protein epitopes. Smaller immunizing doses of MAA-protein conjugate favored the production of antibodies to nonmodified proteins, whereas larger doses induced a strong anti-MAA response. In studies to begin determining a mechanism for the specificity of the response in the absence of adjuvants, peritoneal macrophages were found to bind and degrade MAA-adducted proteins through the use of a scavenger receptor. This indicated that MAA-adducted proteins may be specifically taken up and epitopes presented to the humoral immune system in the absence of adjuvants. Importantly, these are the first data showing that an alcohol-related metabolite can induce an antibody response in the absence of adjuvant and suggesting a mechanism by which antibody to the MAA adduct or its carrier (exogenous or endogenous) proteins may be generated in vivo.

  4. Gaps in knowledge and prospects for research of adjuvanted vaccines.

    Science.gov (United States)

    Seder, Robert; Reed, Steven G; O'Hagan, Derek; Malyala, Padma; D'Oro, Ugo; Laera, Donatello; Abrignani, Sergio; Cerundolo, Vincenzo; Steinman, Lawrence; Bertholet, Sylvie

    2015-06-08

    A panel of researchers working in different areas of adjuvanted vaccines deliberated over the topic, "Gaps in knowledge and prospects for research of adjuvanted vaccines" at, "Enhancing Vaccine Immunity and Value" conference held in July 2014. Several vaccine challenges and applications for new adjuvant technologies were discussed.

  5. Computational prediction of multidisciplinary team decision-making for adjuvant breast cancer drug therapies: a machine learning approach.

    Science.gov (United States)

    Lin, Frank P Y; Pokorny, Adrian; Teng, Christina; Dear, Rachel; Epstein, Richard J

    2016-12-01

    Multidisciplinary team (MDT) meetings are used to optimise expert decision-making about treatment options, but such expertise is not digitally transferable between centres. To help standardise medical decision-making, we developed a machine learning model designed to predict MDT decisions about adjuvant breast cancer treatments. We analysed MDT decisions regarding adjuvant systemic therapy for 1065 breast cancer cases over eight years. Machine learning classifiers with and without bootstrap aggregation were correlated with MDT decisions (recommended, not recommended, or discussable) regarding adjuvant cytotoxic, endocrine and biologic/targeted therapies, then tested for predictability using stratified ten-fold cross-validations. The predictions so derived were duly compared with those based on published (ESMO and NCCN) cancer guidelines. Machine learning more accurately predicted adjuvant chemotherapy MDT decisions than did simple application of guidelines. No differences were found between MDT- vs. ESMO/NCCN- based decisions to prescribe either adjuvant endocrine (97%, p = 0.44/0.74) or biologic/targeted therapies (98%, p = 0.82/0.59). In contrast, significant discrepancies were evident between MDT- and guideline-based decisions to prescribe chemotherapy (87%, p machine learning models. A machine learning approach based on clinicopathologic characteristics can predict MDT decisions about adjuvant breast cancer drug therapies. The discrepancy between MDT- and guideline-based decisions regarding adjuvant chemotherapy implies that certain non-clincopathologic criteria, such as patient preference and resource availability, are factored into clinical decision-making by local experts but not captured by guidelines.

  6. Trastuzumab-Associated Cardiac Events at 8 Years of Median Follow-Up in the Herceptin Adjuvant Trial (BIG 1-01)

    NARCIS (Netherlands)

    de Azambuja, Evandro; Procter, Marion J.; van Veldhuisen, Dirk J.; Agbor-Tarh, Dominique; Metzger-Filho, Otto; Steinseifer, Jutta; Untch, Michael; Smith, Ian E.; Gianni, Luca; Baselga, Jose; Jackisch, Christian; Cameron, David A.; Bell, Richard; Leyland-Jones, Brian; Dowsett, Mitch; Gelber, Richard D.; Piccart-Gebhart, Martine J.; Suter, Thomas M.

    2014-01-01

    Purpose To document the rate and outcome of trastuzumab-associated cardiac dysfunction in patients following 1 or 2 years of adjuvant therapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial comparing 2 years or 1 year of trastuzumab with observation in 5,10

  7. Vitamins as influenza vaccine adjuvant components.

    Science.gov (United States)

    Quintilio, Wagner; de Freitas, Fábio Alessandro; Rodriguez, Dunia; Kubrusly, Flavia Saldanha; Yourtov, Dimitri; Miyaki, Cosue; de Cerqueira Leite, Luciana Cezar; Raw, Isaias

    2016-10-01

    A number of adjuvant formulations were assayed in mice immunized with 3.75 µg of A/California/7/2009 (H1N1) pdm09 influenza vaccine with vitamins A, D and/or E in emulsions or B2 and/or B9 combined with Bordetella pertussis MPLA and/or alum as adjuvants. Squalene was used as positive control, as well as MPLA with alum. The immune response was evaluated by a panel of tests, including a hemagglutination inhibition (HAI) test, ELISA for IgG, IgG1, and IgG2a and IFN-γ, IL-2, IL-6 and IL-10 quantification in splenocyte culture supernatant after stimulus with influenza antigen. Immunological memory was evaluated using a 1/10 dose booster 60 days after the first immunization followed by assessment of the response by HAI, IgG ELISA, and determination of the antibody affinity index. The highest increases in HAI, IgG1 and IgG2a titers were obtained with the adjuvant combinations containing vitamin E, or the hydrophilic combinations containing MPLA and alum or B2 and alum. The IgG1/IgG2a ratio indicates that the response to the combination of B2 with alum would have more Th2 character than the combination of MPLA with alum. In an assay to investigate the memory response, a significant increase in HAI titer was observed with a booster vaccine dose at 60 days after immunization with vaccines containing MPLA with alum or B2 with alum. Overall, of the 27 adjuvant combinations, MPLA with alum and B2 with alum were the most promising adjuvants to be evaluated in humans.

  8. Review article: surgical, neo-adjuvant and adjuvant management strategies in biliary tract cancer.

    Science.gov (United States)

    Skipworth, J R A; Olde Damink, S W M; Imber, C; Bridgewater, J; Pereira, S P; Malagó, M

    2011-11-01

    The majority of patients with cholangiocarcinoma present with advanced, irresectable tumours associated with poor prognosis. The incidence and mortality rates associated with cholangiocarcinoma continue to rise, mandating the development of novel strategies for early detection, improved resection and treatment of residual lesions. To review the current evidence base for surgical, adjuvant and neo-adjuvant techniques in the management of cholangiocarcinoma. A search strategy incorporating PubMed/Medline search engines and utilising the key words biliary tract carcinoma; cholangiocarcinoma; management; surgery; chemotherapy; radiotherapy; photodynamic therapy; and radiofrequency ablation, in various combinations, was employed. Data on neo-adjuvant and adjuvant techniques remain limited, and much of the literature concerns palliation of inoperable disease. The only opportunity for long-term survival remains surgical resection with negative pathological margins or liver transplantation, both of which remain possible in only a minority of selected patients. Neo-adjuvant and adjuvant techniques currently provide only limited success in improving survival. The development of novel strategies and treatment techniques is crucial. However, the shortage of randomised controlled trials is compounded by the low feasibility of conducting adequately powered trials in liver surgery, due to the large sample sizes that are required. © 2011 Blackwell Publishing Ltd.

  9. Side effects in melanoma patients receiving adjuvant interferon alfa-2b therapy: a nurse's perspective.

    Science.gov (United States)

    Rubin, Krista M; Vona, Karen; Madden, Kathleen; McGettigan, Suzanne; Braun, Ilana M

    2012-08-01

    The aim of this review was to examine the toxicity profile of adjuvant interferon (IFN) alfa-2b in melanoma patients from a nursing perspective and to summarize practical information to guide the effective management of common IFN toxicities to improve patient comfort. This is a narrative summary of both research and review articles identified by searching PubMed, National Cancer Institute, and American Cancer Society websites. It also assesses recognized guidelines on the management of adjuvant IFN toxicity relevant to nurses who are caring for patients receiving adjuvant IFN therapy. Adjuvant high-dose IFN alfa-2b (HDI) as compared with observation significantly prolongs relapse-free survival in patients with melanoma at high risk for recurrence after surgical resection; however, treatment compliance and patient quality of life can be compromised by its toxicity profile. HDI toxicities affect a number of organ systems and the majority of patients will experience some side effects. Common toxicities such as flu-like symptoms, fatigue, anorexia, neuropsychiatric symptoms, and laboratory abnormalities are discussed, along with both pharmacological and nonpharmacological management strategies. The considerable side effects of HDI can be managed using established strategies. Oncology nurses play a significant role in the management of patients with melanoma receiving adjuvant HDI, and their prompt recognition of side effects, together with an understanding of effective pharmacological and nonpharmacological interventions, will improve patient comfort; this has the potential to positively influence treatment adherence and completion of the recommended treatment course.

  10. Stage I testicular seminoma: a SEER analysis of contemporary adjuvant radiotherapy trends.

    Science.gov (United States)

    Thong, Alan E; Lichtensztajn, Daphne Y; Almario, Leanne; Ingels, Alexandre; Gomez, Scarlett Lin; Gonzalgo, Mark L

    2013-10-01

    Patients with clinical stage I testicular seminoma have historically been treated with adjuvant radiotherapy in the United States. However, nearly 80% of patients on surveillance will not experience relapse and even with relapse, salvage rates approach 100%. It remains unclear how practice patterns have changed with recently accumulating evidence and changes in guidelines. In a population based setting we evaluated contemporary trends and factors that may affect the use of adjuvant radiotherapy. A total of 8,151 men diagnosed with stage I testicular seminoma from 2000 to 2009 were identified in the national SEER (Surveillance, Epidemiology, and End Results) registry. A multivariate regression model was constructed to analyze the association of year, age, race, socioeconomic status, SEER region, pathological stage and tumor size with the administration of adjuvant radiotherapy. The use of adjuvant radiotherapy decreased significantly from 2000 to 2009. In 2000, 74.7% of patients received radiation, compared with only 37.7% of patients in 2009 (p seminoma has decreased significantly in the last decade. Older age and higher socioeconomic status are associated with higher rates of adjuvant radiotherapy. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. Effects of adjuvants on IgG subclasses elicited by virus-like Particles

    Directory of Open Access Journals (Sweden)

    Visciano Maria Luisa

    2012-01-01

    Full Text Available Abstract Background Virus-Like Particles (VLPs represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C adjuvants, has been evaluated in an animal model. Results Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced TH2 pattern, VLPs formulated with either adjuvant elicited a TH1-biased IgG subclasses (IgG2a and IgG3, with poly(I:C more potent than CpG ODN1826. Conclusions The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.

  12. Beryllium, an adjuvant that promotes gamma interferon production.

    Science.gov (United States)

    Lee, J Y; Atochina, O; King, B; Taylor, L; Elloso, M; Scott, P; Rossman, M D

    2000-07-01

    Beryllium is associated with a human pulmonary granulomatosis characterized by an accumulation of CD4(+) T cells in the lungs and a heightened specific lymphocyte proliferative response to beryllium (Be) with gamma interferon (IFN-gamma) release (i.e., a T helper 1 [Th1] response). While an animal model of Be sensitization is not currently available, Be has exhibited adjuvant effects in animals. The effects of Be on BALB/c mice immunized with soluble leishmanial antigens (SLA) were investigated to determine if Be had adjuvant activity for IFN-gamma production, an indicator of the Th1 response. In this strain of Leishmania-susceptible BALB/c mice, a Th2 response is normally observed after in vivo SLA sensitization and in vitro restimulation with SLA. If interleukin-12 (IL-12) is given during in vivo sensitization with SLA, markedly increased IFN-gamma production and decreased IL-4 production are detected. We show here that when beryllium sulfate (BeSO(4)) was added during in vivo sensitization of BALB/c mice with SLA and IL-12, significantly increased IFN-gamma production and decreased IL-4 production from lymph node and spleen cells were detected upon in vitro SLA restimulation. No specific responses were observed to Be alone. Lymph node and spleen cells from all mice proliferated strongly and comparably upon in vitro restimulation with SLA and with SLA plus Be; no differences were noted among groups of mice that received different immunization regimens. In vivo, when Be was added to SLA and IL-12 for sensitization of BALB/c mice, more effective control of Leishmania infection was achieved. This finding has implications for understanding not only the development of granulomatous reactions but also the potential for developing Be as a vaccine adjuvant.

  13. New generation adjuvants--from empiricism to rational design.

    Science.gov (United States)

    O'Hagan, Derek T; Fox, Christopher B

    2015-06-08

    Adjuvants are an essential component of modern vaccine development. Despite many decades of development, only a few types of adjuvants are currently included in vaccines approved for human use. In order to better understand the reasons that development of some adjuvants succeeded while many others failed, we discuss some of the common attributes of successful first generation adjuvants. Next, we evaluate current trends in the development of second generation adjuvants, including the potential advantages of rationally designed synthetic immune potentiators appropriately formulated. Finally, we discuss desirable attributes of next generation adjuvants. Throughout, we emphasize that the importance of formulation and analytical characterization in all aspects of vaccine adjuvant development is often underappreciated. We highlight the formulation factors that must be evaluated in order to optimize interactions between vaccine antigens, immune potentiators, and particulate formulations, and the resulting effects on safety, biological activity, manufacturability, and stability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. [Gastrointestinal surgeons should master the adjuvant therapy of colorectal cancer].

    Science.gov (United States)

    Gu, Jin; Chen, Pengju

    2015-10-01

    The diagnosis and treatment of colorectal cancer is one of the main diseases of gastrointestinal surgeons. It is very important to master the adjuvant chemotherapy of colorectal cancer for gastrointestinal surgeons. In recent years, with the development of a number of clinical trials and the appearance of new drugs, fluorouracil combined with oxaliplatin had been established as the standard regimen of adjuvant chemotherapy for colorectal cancer. In the current guidelines, stage III( colon cancer is the indication for adjuvant chemotherapy, while stage II( colon cancer should receive adjuvant chemotherapy is uncertain. Unlike colon cancer, adjuvant therapy of rectal cancer is not evidence-based. Especially, the indication and duration of adjuvant chemotherapy for rectal cancer after neoadjuvant chemoradiotherapy remain controversial. Adjuvant therapy of colorectal cancer still needs further investigation.

  15. Meta-Analysis on Randomized Controlled Trials of Vaccines with QS-21 or ISCOMATRIX Adjuvant: Safety and Tolerability.

    Directory of Open Access Journals (Sweden)

    Emilia Bigaeva

    Full Text Available QS-21 shows in vitro hemolytic effect and causes side effects in vivo. New saponin adjuvant formulations with better toxicity profiles are needed. This study aims to evaluate the safety and tolerability of QS-21 and the improved saponin adjuvants (ISCOM, ISCOMATRIX and Matrix-M™ from vaccine trials.A systematic literature search was conducted from MEDLINE, EMBASE, Cochrane library and Clinicaltrials.gov. We selected for the meta-analysis randomized controlled trials (RCTs of vaccines adjuvanted with QS-21, ISCOM, ISCOMATRIX or Matrix-M™, which included a placebo control group and reported safety outcomes. Pooled risk ratios (RRs and their 95% confidence intervals (CIs were calculated using a random-effects model. Jadad scale was used to assess the study quality.Nine RCTs were eligible for the meta-analysis: six trials on QS-21-adjuvanted vaccines and three trials on ISCOMATRIX-adjuvanted, with 907 patients in total. There were no studies on ISCOM or Matrix-M™ adjuvanted vaccines matching the inclusion criteria. Meta-analysis identified an increased risk for diarrhea in patients receiving QS21-adjuvanted vaccines (RR 2.55, 95% CI 1.04-6.24. No increase in the incidence of the reported systemic AEs was observed for ISCOMATRIX-adjuvanted vaccines. QS-21- and ISCOMATRIX-adjuvanted vaccines caused a significantly higher incidence of injection site pain (RR 4.11, 95% CI 1.10-15.35 and RR 2.55, 95% CI 1.41-4.59, respectively. ISCOMATRIX-adjuvanted vaccines also increased the incidence of injection site swelling (RR 3.43, 95% CI 1.08-10.97.Our findings suggest that vaccines adjuvanted with either QS-21 or ISCOMATRIX posed no specific safety concern. Furthermore, our results indicate that the use of ISCOMATRIX enables a better systemic tolerability profile when compared to the use of QS-21. However, no better local tolerance was observed for ISCOMATRIX-adjuvanted vaccines in immunized non-healthy subjects. This meta-analysis is limited by the

  16. Assessment of the adjuvant activity of mesoporous silica nanoparticles in recombinant Mycoplasma hyopneumoniae antigen vaccines

    Directory of Open Access Journals (Sweden)

    Veridiana Gomes Virginio

    2017-01-01

    Full Text Available The adjuvant potential of two mesoporous silica nanoparticles (MSNs, SBa-15 and SBa-16, was assessed in combination with a recombinant HSP70 surface polypeptide domain from Mycoplasma hyopneumoniae, the etiological agent of porcine enzootic pneumonia (PEP. The recombinant antigen (HSP70212-600, previously shown as immunogenic in formulation with classic adjuvants, was used to immunize BALB/c mice in combination with SBa-15 or SBa-16 MSNs, and the effects obtained with these formulations were compared to those obtained with alum, the adjuvant traditionally used in anti-PEP bacterins. The HSP70212-600 + SBa-15 vaccine elicited a strong humoral immune response, with high serum total IgG levels, comparable to those obtained using HSP70212-600 + alum. The HSP70212-600 + SBa-16 vaccine elicited a moderate humoral immune response, with lower levels of total IgG. The cellular immune response was assessed by the detection of IFN-γ, IL-4 and IL-10 in splenocyte culture supernatants. The HSP70212-600 + SBa-15 vaccine increased IFN-γ, IL-4 and IL-10 levels, while no stimulation was detected with the HSP70212-600 + SBa-16 vaccine. The HSP70212-600 + SBa-15 vaccine induced a mixed Th1/Th2-type response, with an additional IL-10 mediated anti-inflammatory effect, both of relevance for an anti-PEP vaccine. Alum adjuvant controls stimulated an unspecific cellular immune response, with similar levels of cytokines detected in mice immunized either with HSP70212-600 + alum or with the adjuvant alone. The better humoral and cellular immune responses elicited in mice indicated that SBa-15 has adjuvant potential, and can be considered as an alternative to the use of alum in veterinary vaccines. The use of SBa-15 with HSP70212-600 is also promising as a potential anti-PEP subunit vaccine formulation.

  17. The effect of different adjuvants on immune parameters and protection following vaccination of sheep with a larval-specific antigen of the gastrointestinal nematode, Haemonchus contortus.

    Directory of Open Access Journals (Sweden)

    David Piedrafita

    Full Text Available It has recently been recognised that vaccine adjuvants play a critical role in directing the nature of a vaccine induced effector response. In the present study, several adjuvants were evaluated for their ability to protect sheep after field vaccination with the larval-specific Haemonchus contortus antigen, HcsL3. Using a suboptimal antigen dose, aluminium adjuvant was shown to reduce the cumulative faecal egg counts (cFEC and worm burden by 23% and 25% respectively, in agreement with a previous study. The addition of Quil A to the aluminium-adjuvanted vaccine brought cFEC back to control levels. Vaccination with the adjuvant DEAE-dextran almost doubled the protection compared to the aluminium-adjuvanted vaccine resulting in 40% and 41% reduction in cFEC and worm counts compared to controls. Examination of skin responses following i.d. injection of exsheathed L3, revealed that cFEC was negatively correlated with wheal size and tissue eosinophils for the DEAE-dextran and aluminium-adjuvanted groups respectively. These studies have for the first time shown the potential of DEAE-dextran adjuvant for helminth vaccines, and discovered significant cellular correlates of vaccine-induced protection.

  18. Sucrose fatty acid sulphate esters as novel vaccine adjuvants: effect of the chemical composition

    NARCIS (Netherlands)

    Blom, A.G.; Hilgers, L.A.T.

    2004-01-01

    Adjuvant activity of novel, synthetic sucrose derivatives towards a recombinant glycoprotein was determined in large, non-rodent animal species. Compared to antigen alone, up to 3000-fold higher virus neutralizing antibody titres (VNTs) and 10-fold higher cellular responses against classical swine f

  19. Fluorescence imaging for investigating the efficiency of formulations, adjuvants and application systems

    NARCIS (Netherlands)

    Ruiter, de H.; Schoor, van der R.; Jalink, H.

    2005-01-01

    Several herbicides reduce, directly or indirectly, the efficiency of photosynthesis of plants. As a consequence, the fluorescence of the chlorophyll increases. The relative increase of fluorescence [(Fm-F0)/Fm] can be used to compare the influence of formulations and adjuvants on the activity of her

  20. Persistent pain, sensory disturbances and functional impairment after adjuvant chemotherapy for breast cancer

    DEFF Research Database (Denmark)

    Andersen, Kenneth Geving; Jensen, Maj-Britt; Kehlet, Henrik

    2012-01-01

    Background. Taxanes used in adjuvant therapy for breast cancer are neurotoxic, and thereby being a potential risk factor for persistent pain after breast cancer treatment (PPBCT) and sensory disturbances. The purpose was to compare patients treated with cyclophosphamide, epirubicin and fluorourac...

  1. Sucrose fatty acid sulphate esters as novel vaccine adjuvants: effect of the chemical composition

    NARCIS (Netherlands)

    Blom, A.G.; Hilgers, L.A.T.

    2004-01-01

    Adjuvant activity of novel, synthetic sucrose derivatives towards a recombinant glycoprotein was determined in large, non-rodent animal species. Compared to antigen alone, up to 3000-fold higher virus neutralizing antibody titres (VNTs) and 10-fold higher cellular responses against classical swine

  2. Evaluation of Montanide ISA 71 VG adjuvant during profilin vaccination against experimental coccidiosis

    Science.gov (United States)

    Chickens were immunized subcutaneously with an Eimeria recombinant profilin protein plus ISA 70 VG (ISA 70) or ISA 71 VG (ISA 71) water-in-oil adjuvants, or with profilin alone, and comparative RNA microarray hybridizations were performed to ascertain global transcriptome changes induced by profilin...

  3. The adherence and tolerance of adjuvant endocrine therapy in geriatric breast cancer patients

    Directory of Open Access Journals (Sweden)

    Meng-Ting Peng

    2016-09-01

    Conclusions: The completion rate for patients who underwent oral ET in our study was similar to previous studies. The switch method of adjuvant oral endocrine therapy demonstrated a better tolerance and adherence in elderly breast cancer patients, compared with tamoxifen or aromatase inhibitor alone.

  4. The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes

    DEFF Research Database (Denmark)

    Korsholm, Karen Smith; Agger, Else Marie; Foged, Camilla

    2007-01-01

    Cationic liposomes are being used increasingly as efficient adjuvants for subunit vaccines but their precise mechanism of action is still unknown. Here, we investigated the adjuvant mechanism of cationic liposomes based on the synthetic amphiphile dimethyldioctadecylammonium (DDA). The liposomes...... concentrations. This efficient adsorption onto the liposomes led to an enhanced uptake of OVA by BM-DCs as assessed by flow cytometry and confocal fluorescence laser-scanning microscopy. This was an active process, which was arrested at 4 degrees and by an inhibitor of actin-dependent endocytosis, cytochalasin D....... In vivo studies confirmed the observed effect because adsorption of OVA onto DDA liposomes enhanced the uptake of the antigen by peritoneal exudate cells after intraperitoneal injection. The liposomes targeted antigen preferentially to antigen-presenting cells because we only observed a minimal uptake...

  5. Glucocorticosteroids: as Adjuvant Therapy for Bacterial Infections

    OpenAIRE

    2015-01-01

    Glucocorticoids (GCs), synthetic analogues of the natural steroid hormones, are well known for their antiinflammatory and immunosuppressive properties in the periphery. They are widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, and transplant rejection. Nowadays, GCs are claimed to have a beneficial role being as adjunct therapy in various infections. Different studies have been conducted to investigate their use as adjuvant therapy for different bact...

  6. Inflammatory responses following intramuscular and subcutaneous immunization with aluminum-adjuvanted or non-adjuvanted vaccines.

    Science.gov (United States)

    Kashiwagi, Yasuyo; Maeda, Mika; Kawashima, Hisashi; Nakayama, Tetsuo

    2014-06-05

    Aluminum-adjuvanted vaccines are administered through an intramuscular injection (IM) in the US and EU, however, a subcutaneous injection (SC) has been recommended in Japan because of serious muscle contracture previously reported following multiple IMs of antibiotics. Newly introduced adjuvanted vaccines, such as the human papillomavirus (HPV) vaccines, have been recommended through IM. In the present study, currently available vaccines were evaluated through IM in mice. Aluminum-adjuvanted vaccines induced inflammatory nodules at the injection site, which expanded into the intra-muscular space without any muscle degeneration or necrosis, whereas non-adjuvanted vaccines did not. These nodules consisted of polymorph nuclear neutrophils with some eosinophils within the initial 48h, then monocytes/macrophages 1 month later. Inflammatory nodules were observed 6 months after IM, had decreased in size, and were absorbed 12 months after IM, which was earlier than that after SC. Cytokine production was examined in the injected muscular tissues and AS04 adjuvanted HPV induced higher IL-1β, IL-6, KC, MIP-1, and G-CSF levels in muscle tissues than any other vaccine, but similar serum cytokine profiles were observed to those induced by the other vaccines. Currently available vaccines did not induce muscular degeneration or fibrotic scar as observed with muscle contracture caused by multiple IMs of antibiotics in the past.

  7. Adjuvant and neoadjuvant treatment in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies,ranking 4th among causes for cancer-related death in the Western world including the United States.Surgical resection offers the only chance of cure,but only 15 to 20 percent of cases are potentially resectable at presentation.Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy.Currently there is no consensus around the world on what constitutes "standard"adjuvant therapy for pancreatic cancer.This controversy derives from several studies,each fraught with its own limitations.Standards of care also vary somewhat with regard to geography and economy,for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe.Regardless of the efforts in adjuvant and neoadjuvant improved therapy,the major goal to combat pancreatic cancer is to find diagnostic markers,identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients.In this review,authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

  8. Effects of 3% trehalose as an adjuvant treatment after LASIK

    Science.gov (United States)

    Mateo Orobia, Antonio J; Casas Pascual, Paula; Cristóbal Bescós, José Á; Perez García, Diana; Peiro Embid, Carlos; del Buey Sayas, M Ángeles; Korobko Kulikova, Valentyna; Lafuente Ojeda, Noelia

    2017-01-01

    Purpose To evaluate the effect of 3% trehalose as an adjuvant in the standard treatment after laser-assisted in situ keratomileusis. Design Interventional prospective comparative single-blind study. Setting Department of Ophthalmology, Hospital Quirón Zaragoza, Spain. Methods A total of 26 eyes (13 patients) were included, of which 12 eyes (group 1) received conventional treatment with lubricant drops of hyaluronic acid (0.15%) and 14 eyes (group 2) received, additionally, an ophthalmic solution of 3% trehalose. Pre- and postoperative quality-of-life tests and vital stains, tear breakup time, and osmolarity measurements were made. Results We obtained statistically significant differences between the groups in the Symptom Assessment in Dry Eye test in all visits with respect to severity, and in the postoperative day 1 visit with respect to frequency, in all cases favoring the trehalose treatment. The values of osmolarity were not significantly different between groups. However, we did find significant differences in the Oxford scale in day 90 for the trehalose treatment (P<0.001), and in the National Eye Institute scale in day 30 (P=0.02). Conclusion The results of this exploratory study indicate that the adjuvant treatment with 3% trehalose could be superior with respect to the standard treatment, with improvements in the objective and subjective parameters of tear quality. PMID:28243058

  9. Use of melatonin as an adjuvant therapy in neonatal sepsis.

    Science.gov (United States)

    El Frargy, M; El-Sharkawy, H M; Attia, G F

    2015-01-01

    The objective of this study is to evaluate the therapeutic efficacy of melatonin as an adjuvant therapy in treating neonatal sepsis. A prospective clinical trial study was conducted on 50 infants with neonatal sepsis diagnosed on the basis of both clinical and laboratory criteria. Enrolled infants were divided into two groups. Intervention group (n = 25) received melatonin and antibiotics, while the control group (n = 25) was treated with antibiotics only. Melatonin was administered as a single oral dose of 20 mg and antibiotics were administered according to a standard protocol. Both groups were compared using a predefined sepsis score utilizing both clinical and laboratory parameters. There was no significant difference in sepsis score between both groups before starting melatonin (p-value = 0.99), while there was significant difference in sepsis score between groups after 24 hours, 48 hours and 72 hours of starting melatonin with (p-value = 0.008, 0.006 and 0.002, respectively). There was significant improvement sepsis score in both groups with more improvement of sepsis score in the intervention group. Administration of melatonin as an adjuvant therapy in the treatment of neonatal sepsis is associated with improvement of clinical and laboratory outcomes.

  10. Mucosal and systemic adjuvant activity of alphavirus replicon particles

    Science.gov (United States)

    Thompson, Joseph M.; Whitmore, Alan C.; Konopka, Jennifer L.; Collier, Martha L.; Richmond, Erin M. B.; Davis, Nancy L.; Staats, Herman F.; Johnston, Robert E.

    2006-03-01

    Vaccination represents the most effective control measure in the fight against infectious diseases. Local mucosal immune responses are critical for protection from, and resolution of, infection by numerous mucosal pathogens. Antigen processing across mucosal surfaces is the natural route by which mucosal immunity is generated, as peripheral antigen delivery typically fails to induce mucosal immune responses. However, we demonstrate in this article that mucosal immune responses are evident at multiple mucosal surfaces after parenteral delivery of Venezuelan equine encephalitis virus replicon particles (VRP). Moreover, coinoculation of null VRP (not expressing any transgene) with inactivated influenza virions, or ovalbumin, resulted in a significant increase in antigen-specific systemic IgG and fecal IgA antibodies, compared with antigen alone. Pretreatment of VRP with UV light largely abrogated this adjuvant effect. These results demonstrate that alphavirus replicon particles possess intrinsic systemic and mucosal adjuvant activity and suggest that VRP RNA replication is the trigger for this activity. We feel that these observations and the continued experimentation they stimulate will ultimately define the specific components of an alternative pathway for the induction of mucosal immunity, and if the activity is evident in humans, will enable new possibilities for safe and inexpensive subunit and inactivated vaccines. vaccine vector | Venezuelan equine encephalitis virus | viral immunology | RNA virus

  11. Survival After Chemoradiation in Resected Pancreatic Cancer: The Impact of Adjuvant Gemcitabine

    Energy Technology Data Exchange (ETDEWEB)

    Baschnagel, Andrew; Shah, Chirag [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Margolis, Jeffrey; Nadeau, Laura [Department of Medical Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Stein, Julie; Jury, Robert [Department of Surgery, William Beaumont Hospital, Royal Oak, Michigan (United States); Robertson, John M., E-mail: jrobertson@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States)

    2012-07-01

    Purpose: To evaluate survival in patients with resected pancreatic cancer treated with concurrent chemoradiation with or without adjuvant gemcitabine (Gem). Methods and Materials: From 1998 to 2010, 86 patients with pancreatic adenocarcinoma who underwent resection were treated with adjuvant concurrent chemoradiation. Thirty-four patients received concurrent 5-fluorouracil-based chemoradiation (5-FU/RT) with traditional field radiation (range, 45-61.2 Gy; median, 50.4 Gy) without further adjuvant therapy. Thirty patients received traditional field 5-FU/RT (range, 45-60.4 Gy; median, 50.4 Gy) with Gem (1,000 mg/m{sup 2} weekly) either before and after radiotherapy or only after radiotherapy. Twenty-two patients received concurrent full-dose Gem (1,000 mg/m{sup 2} weekly)-based chemoradiation (Gem/RT), consisting of involved-field radiation (range, 27-38 Gy; median, 36 Gy) followed by further adjuvant Gem. Results: The median age of the cohort was 65 years (range, 40-80 years). Of the patients, 58 had T3 tumors (67%), 22 had T2 tumors (26%), and 6 had T1 tumors (7%). N1 disease was present in 61 patients (71%), whereas 18 patients (21%) had R1 resections. Performance status, lymph node status, and margin status were all similar among the treatment groups. Median follow-up was 19.0 months. Median overall survival (OS) (19.2 months, 19.0 months, and 21.0 months) and 3-year OS rates (26.5%, 27.2%, and 32.1%) were similar among patients with 5-FU/RT with no adjuvant Gem, those with 5-FU/RT with adjuvant Gem, and those with Gem/RT with adjuvant Gem, respectively (p = 0.88). Patients who received adjuvant Gem had a similar median OS (22.1 months) and 3-year OS rate (29%) compared to patients who did not (19.2 months and 26.5%, respectively) (p = 0.62). There was a trend for improved 3-year OS rates in patients with R0 vs. R1 resections (28.1% vs. 14.2%, p = 0.06) and in patients with T1 and T2 vs. T3 tumors (38% vs. 20%, p = 0.09). Node-negative patients had an improved 3

  12. Adjuvant chemotherapy for early-stage cervical cancer.

    Science.gov (United States)

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-04-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  13. Neoadjuvant vs adjuvant pelvic radiotherapy for locally advanced rectal cancer:Which is superior?

    Institute of Scientific and Technical Information of China (English)

    Sarah Popek; Vassiliki Liana Tsikitis

    2011-01-01

    The treatment of locally advanced rectal cancer including timing and dosage of radiotherapy,degree of sphincter preservation with neoadjuvant radiotherapy,and short and long term effects of radiotherapy are controversial topics.The MEDLINE,Cochrane Library databases,and meeting proceedings from the American Society of Clinical Oncology,were searched for reports of randomized controlled trials and meta-analyses comparing neoadjuvant and adjuvant radiotherapy with surgery to surgery alone for rectal cancer.Neoadjuvant radiotherapy shows superior results in terms of local control compared to adjuvant radiotherapy.Neither adjuvant or neoadjuvant radiotherapy impacts overall survival.Short course versus long course neoadjuvant radiotherapy remains controversial.There is insufficient data to conclude that neoadjuvant therapy improves rates of sphincter preserving surgery.Radiation significantly impacts anorectal and sexual function and includes both acute and long term toxicity.Data demonstrate that neoadjuvant radiation causes less toxicity compared to adjuvant radiotherapy,and specifically short course neoadjuvant radiation results in less toxicity than long course neoadjuvant radiation.Neoadjuvant radiotherapy is the preferred modality for administering radiation in locally advanced rectal cancer.There are significant side effects from radiation,including anorectal and sexual dysfunction,which may be less with short course neoadjuvant radiation.

  14. Successful adjuvant bi-weekly gemcitabine chemotherapy for pancreatic cancer without impairing patients’ quality of life

    Directory of Open Access Journals (Sweden)

    Toyama Yoichi

    2013-01-01

    Full Text Available Abstract Background Although adjuvant gemcitabine (GEM chemotherapy for pancreatic cancer is standard, the quality of life (QOL in those patients is still impaired by the standard regimen of GEM. Therefore, we studied whether mild dose-intensity adjuvant chemotherapy with bi-weekly GEM administration could provide a survival benefit with acceptable QOL to the patients with pancreatic cancer. Methods After a phase I trial, an adjuvant bi-weekly 1,000 mg/m2 of GEM chemotherapy was performed in 58 patients with pancreatic cancer for at least 12 courses (Group A. In contrast, 36 patients who declined the adjuvant bi-weekly GEM chemotherapy underwent traditional adjuvant 5FU-based chemotherapy (Group B. Careful periodical follow-ups for side effects of GEM and disease recurrence, and assessment of patients’ QOL using the EORTC QOL questionnaire (QLQ-C30 and pancreatic cancer-specific supplemental module (QLQ-PAN26 were performed. Retrospectively, the degree of side effects, patients’ QOL, compliance rate, disease-free survival (DFS, and overall survival (OS in Group A were compared with those in Group B. Results No severe side effects (higher than Grade 2 according to the common toxicity criteria of ECOG were observed, except for patients in Group B, who were switched to the standard GEM chemotherapy. Patients’ QOL was better in Group A than B (fatigue: 48.9 ± 32.1 versus 68.1 ± 36.3, nausea and vomiting: 26.8 ± 20.4 versus 53.7 ± 32.6, diarrhea: 21.0 ± 22.6 versus 53.9 ± 38.5, difficulty gaining weight: 49.5 ± 34.4 versus 67.7 ± 40.5, P P P Conclusions Adjuvant chemotherapy with bi-weekly GEM offered not only the advantage of survival benefits but the excellent compliance with acceptable QOL for postoperative pancreatic cancer patients.

  15. Evaluation of efficacy of saponin and freund's incomplete adjuvanted paratuberculosis vaccine in murine model

    Directory of Open Access Journals (Sweden)

    Jubeda Begum

    2014-07-01

    Full Text Available Aim: To compare the efficacy between saponin adjuvanted paratuberculosis killed vaccine and Freund's incomplete (FIC adjuvanted paratuberculosis vaccine in mice model. Materials and Methods: The study was conducted for a period of 11 months using 80 Swiss albino mice by dividing into four groups (Group I-mice vaccinated with killed Mycobacterium avium subspp. paratuberculosis (MAP adjuvanted with saponin, Group II- for FIC, Group III- Saponin control and Gr IV- FIC control. Faecal shedding, changes in body weight, presence of local reactions and clinical symptoms, were evaluated. Serological assays for humoral and cell mediated immune response were determined by agar gel immunodiffusion (AGID and nitric oxide test (NO respectively. A total of 76 serum samples, 52 faecal samples and 20 tissue samples were collected at different intervals during the study period. ZN staining; AGID test and nitric oxide test were employed for analysis of samples. Results: A total of 38 samples (37 faecal and 1 tissue sample and 18 serum samples were recorded as positive by ZN staining and AGID test respectively from all four groups of mice. Significant decrease in faecal shedding of organisms was observed in Group I mice vaccinated with saponin adjuvanted vaccine in comparison to Group II. Gain in body weight of Group I mice was recorded as higher than Group II. NO test revealed increase in the concentration of NO level in both vaccinated group but more significant in Group I. Conclusion: The tests results obtained revealed that killed MAP vaccine adjuvanted with saponin have higher protective efficacy in terms of reduced faecal shedding, gain in body weight, less side effects, absence of attributable specific symptoms of Johne's disease, etc. in comparison to killed MAP vaccine adjuvanted with FIC. The present study also reveals that AGID and NO estimation tests are specific tests which can be employed for diagnosis and comparison of efficacy of paratuberculosis

  16. [Assessment of the MF59-adjuvanted pandemic influenza A/H1N1 vaccine. Systematic review of literature].

    Science.gov (United States)

    Ruiz-Aragón, J; Grande Tejada, A M; Márquez-Peláez, S; Molina Linde, J M; Yang, R

    2013-10-01

    To assess the efficacy and safety of MF59-adjuvanted pandemic influenza A/H1N1 vaccine in children. A systematic review of the literature was performed after searching the MedLine and Embase electronic databases, and manual search in specialties journals, with MeSH terms and and free terms. Inclusion criteria were clinical trials with children vaccinated with MF59-adjuvanted influenza A/H1N1 vaccine, compared with other vaccines doses with/without MF59-adjuvanted. The immunogenicity and safety of the vaccine was recorded. The quality of the studies included was assessed by CASPe checklist. Four clinical trials with moderate quality were selected. The local and systemic adverse effects were rare and mild, with no differences between groups. Seroconversion and seroprotection levels were higher with MF59-adjuvanted vaccines. Antibody titres were also higher with the adjuvant vaccines. The adjuvant vaccine has a good efficacy and safety profile. The adverse effects that may occur are common and appear similarly in both vaccination groups. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  17. Incidence of radiation toxicity in cervical cancer and endometrial cancer patients treated with radiotherapy alone versus adjuvant radiotherapy

    Science.gov (United States)

    Roszak, Andrzej; Wareńczak-Florczak, Żaneta; Bratos, Krystyna; Milecki, Piotr

    2012-01-01

    Aim The study was made to evaluate early and late toxicity in a diversified group of patients receiving definitive or adjuvant radiotherapy in terms of clinical diagnosis and treatment methods. Background Radiotherapy is a standard way of treatment in cervical and endometrial cancer patients, both as definitive and adjuvant therapy. But every radiation treatment may be involved with toxicity. Materials and methods A detailed analysis was performed of 263 patients with gynaecological cancer treated with definitive (90 patients with cervical cancer received radiochemotherapy or radiotherapy exclusively) and adjuvant radiotherapy (38 with cervical and 135 with endometrial cancer). Results Acute reactions were found in 51.3% and late reactions were found in 14.8% of patients. It was stated that early (p radiotherapy. The analysis of the whole group revealed higher rate of toxicity, both early and late, in the gastrointestinal tract than in the urinary system (p radiotherapy group than in the adjuvant one. The occurrence of side effects was associated with the prolongation of total irradiation time due to necessary interruptions of radiotherapy. The comparison of the subgroups showed that interruptions occurred more frequently in patients receiving definitive rather than adjuvant radiotherapy (17.7–2.9%). Conclusions Definitive radiotherapy compared with adjuvant treatment may by associated with higher percentage of side effects caused by dose of therapy and correlation with chemotherapy. PMID:24377035

  18. From discovery to licensure, the Adjuvant System story

    Science.gov (United States)

    Garçon, Nathalie; Di Pasquale, Alberta

    2017-01-01

    ABSTRACT Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80 years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it. This knowledge opens the door to more rational vaccine design with implications for developing new and better vaccines. PMID:27636098

  19. Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy.

    Science.gov (United States)

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.

  20. Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

    Science.gov (United States)

    Wu, Peipei; Lu, Jihu; Feng, Lei; Wu, Hongzhuan; Zhang, Xuehua; Mei, Mei; Hou, Jibo; Liu, Xiufan; Tang, Yinghua

    2017-01-01

    We previously described that immunopotentiators, CVCVA5, increased the efficacy of H5 and H9 subtype avian influenza vaccines in chickens, ducks, and geese. In this study, we further investigated the effects of the CVCVA5 for improving the efficacy of other univalent or multivalent inactivated vaccines. The immune response administrated with half-dose of monovalent vaccine plus CVCVA5 were higher than those of one dose of monovalent vaccine without immunopotentiators as measured by levels of antibodies from serum, tears and bronchoalveolar lavage fluids, and cytokines of IFNγ and IL-4 from serum. Vaccines included the univalent vaccine of Newcastle Disease virus (ND), Egg Drop Syndrome virus (EDS), Infectious Bronchitis virus (IB), and Infectious Bursal Disease virus (IBD). The CVCVA5 also improved the immune response of both ND and IBD vaccines with less dosage. The sterile protective immunity was monitored with one- or a half-dose of adjuvanted ND vaccine or one dose of adjuvanted IBD vaccine, respectively. The improved immune efficacy was observed in a half-dose of adjuvanted bivalent vaccines compared to one dose of vaccines without CVCVA5 as measured by the antibody levels, including bivalent vaccine of ND-H9, ND-IB, and ND-IBD. The CVCVA5 also boosted the immune efficacy of the tetravalent vaccine (ND-IB-EDS-H9). A half-dose of adjuvanted commercial vaccine or 75% antigen-sparing adjuvanted vaccine elicited similar antibody levels to those of one dose non-adjuvanted commercial vaccines. The CVCVA5 improved the effect of a booster vaccination as measured by the antibody levels against H5 or H9 virus antigens, in which chickens primed with the adjuvanted ND-IB vaccines given a booster with H5–H9 bivalent vaccines without CVCVA5 using 5-day intervals. The inflammatory response may contribute to these additional effects by increasing the levels of IFNγ and IL-4 after the injection of the adjuvanted ND-IB vaccines. Results indicated that the CVCVA5 improved

  1. Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

    Directory of Open Access Journals (Sweden)

    Peipei Wu

    2017-05-01

    Full Text Available We previously described that immunopotentiators, CVCVA5, increased the efficacy of H5 and H9 subtype avian influenza vaccines in chickens, ducks, and geese. In this study, we further investigated the effects of the CVCVA5 for improving the efficacy of other univalent or multivalent inactivated vaccines. The immune response administrated with half-dose of monovalent vaccine plus CVCVA5 were higher than those of one dose of monovalent vaccine without immunopotentiators as measured by levels of antibodies from serum, tears and bronchoalveolar lavage fluids, and cytokines of IFNγ and IL-4 from serum. Vaccines included the univalent vaccine of Newcastle Disease virus (ND, Egg Drop Syndrome virus (EDS, Infectious Bronchitis virus (IB, and Infectious Bursal Disease virus (IBD. The CVCVA5 also improved the immune response of both ND and IBD vaccines with less dosage. The sterile protective immunity was monitored with one- or a half-dose of adjuvanted ND vaccine or one dose of adjuvanted IBD vaccine, respectively. The improved immune efficacy was observed in a half-dose of adjuvanted bivalent vaccines compared to one dose of vaccines without CVCVA5 as measured by the antibody levels, including bivalent vaccine of ND-H9, ND-IB, and ND-IBD. The CVCVA5 also boosted the immune efficacy of the tetravalent vaccine (ND-IB-EDS-H9. A half-dose of adjuvanted commercial vaccine or 75% antigen-sparing adjuvanted vaccine elicited similar antibody levels to those of one dose non-adjuvanted commercial vaccines. The CVCVA5 improved the effect of a booster vaccination as measured by the antibody levels against H5 or H9 virus antigens, in which chickens primed with the adjuvanted ND-IB vaccines given a booster with H5–H9 bivalent vaccines without CVCVA5 using 5-day intervals. The inflammatory response may contribute to these additional effects by increasing the levels of IFNγ and IL-4 after the injection of the adjuvanted ND-IB vaccines. Results indicated that the

  2. Survival Benefit of Adjuvant Radiation Therapy for Gastric Cancer following Gastrectomy and Extended Lymphadenectomy

    Directory of Open Access Journals (Sweden)

    R. A. Snyder

    2012-01-01

    Full Text Available Purpose. Although randomized trials suggest a survival benefit of adjuvant chemotherapy and radiation therapy (XRT for gastric adenocarcinoma, its use in patients who undergo an extended lymphadenectomy is less clear. The purpose of this study was to determine if a survival benefit exists in gastric cancer patients who receive adjuvant XRT following resection with extended lymphadenectomy. Methods. The SEER registry was queried for records of patients with resected gastric adenocarcinoma from 1988 to 2007. Multivariable Cox regression models were used to assess independent prognostic factors affecting overall survival (OS and disease-specific survival (DSS. Results. Of 15,060 patients identified, 3,208 (21% received adjuvant XRT. Adjuvant XRT was independently associated with improved OS (HR 0.67, CI 0.64–0.71 and DSS (HR 0.69, CI 0.65–0.73 in stages IB through IV (M0. This OS and DSS benefit persisted regardless of the extent of lymphadenectomy. Furthermore, lymphadenectomy with >25 LN resected was associated with improved OS and DSS compared with 25 LNs results in improved OS and DSS compared with patients who have fewer LNs resected.

  3. Tubular carcinoma of the breast: prognosis and response to adjuvant systemic therapy.

    Science.gov (United States)

    Kitchen, P R; Smith, T H; Henderson, M A; Goldhirsch, A; Castiglione-Gertsch, M; Coates, A S; Gusterson, B; Brown, R W; Gelber, R D; Collins, J P

    2001-01-01

    Tubular carcinoma of the breast is an uncommon and usually small tumour, and is thought to have a favourable prognosis. The present study examined the long-term prognosis of patients with tubular breast carcinoma and the roles of axillary dissection and adjuvant therapy. Eighty-six tubular cases were identified from a large worldwide database of 9520 breast carcinoma patients entered into randomized adjuvant therapy trials run by the International Breast Cancer Study Group from 1978 to 1999. These patients were followed for a median of 12 years. Forty-two (49%) cases were node-positive, of which 33 (79%) had 1-3 nodes involved. Ten (32%) of the 31 smaller tumours (survival (P = 0.006) and survival (P survival was similar for node-positive and node-negative tubular carcinoma. Overall, 71 patients (83%) received some form of adjuvant systemic therapy. Of the 86 cases, 43 (50%) received more than one course of chemotherapy. There was an 85% decrease in the risk of death for patients who received more than one course of chemotherapy compared to those who did not (hazard ratio 0.15, 95% confidence interval (CI): 0.03-0.82; P = 0.03). Compared to other histological types of breast cancer, tubular carcinoma has a better long-term prognosis. Adjuvant chemotherapy may further improve prognosis and involvement of axillary nodes may not be an indicator for early death due to breast carcinoma.

  4. Towards an understanding of the adjuvant action of aluminium

    Science.gov (United States)

    Marrack, Philippa; McKee, Amy S.; Munks, Michael W.

    2011-01-01

    The efficacy of vaccines depends on the presence of an adjuvant in conjunction with the antigen. Of these adjuvants, the ones that contain aluminium, which were first discovered empirically in 1926, are currently the most widely used. However, a detailed understanding of their mechanism of action has only started to be revealed. In this Timeline article, we briefly describe the initial discovery of aluminium adjuvants and discuss historically important advances. We also summarize recent progress in the field and discuss their implications and the remaining questions on how these adjuvants work. PMID:19247370

  5. Immunogenicity and immunization costs of adjuvanted versus non-adjuvanted hepatitis B vaccine in chronic kidney disease patients.

    Science.gov (United States)

    Vilajeliu, Alba; Sequera, Víctor-Guillermo; García-Basteiro, Alberto L; Sicuri, Elisa; Aldea, Marta; Velasco, César; Bayas, José M

    2016-09-01

    Hepatitis B virus (HBV) vaccination is recommended for all susceptible chronic pre-hemodialysis and hemodialysis patients. This study assessed the immunogenicity of HBV vaccines (adjuvanted and non-adjuvanted) in chronic kidney disease patients vaccinated at the Hospital Clinic of Barcelona (Spain) between January 2007 and July 2012. In addition, the costs for the health system were evaluated accor-ding to the proportion of vaccine responders after receiving either vaccine. Patients receiving 3 doses of hepatitis B adjuvanted vaccine were 3 times more likely to seroconvert than patients immunized with non-adjuvanted vaccines, OR 3.56 (95% CI 1.84-6.85). This resulted in fewer patients requiring a second course of HBV vaccination and fewer outpatient visits, saving more than €9,500 per 100 patients. The higher immunogenicity of the adjuvanted HBV vaccine would counterbalance the lower costs associated with the non-adjuvanted vaccine.

  6. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant.

    Science.gov (United States)

    Coler, Rhea N; Bertholet, Sylvie; Moutaftsi, Magdalini; Guderian, Jeff A; Windish, Hillarie Plessner; Baldwin, Susan L; Laughlin, Elsa M; Duthie, Malcolm S; Fox, Christopher B; Carter, Darrick; Friede, Martin; Vedvick, Thomas S; Reed, Steven G

    2011-01-26

    Innate immune responses to vaccine adjuvants based on lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, are driven by Toll-like receptor (TLR) 4 and adaptor proteins including MyD88 and TRIF, leading to the production of inflammatory cytokines, type I interferons, and chemokines. We report here on the characterization of a synthetic hexaacylated lipid A derivative, denoted as glucopyranosyl lipid adjuvant (GLA). We assessed the effects of GLA on murine and human dendritic cells (DC) by combining microarray, mRNA and protein multiplex assays and flow cytometry analyses. We demonstrate that GLA has multifunctional immunomodulatory activity similar to naturally-derived monophosphory lipid A (MPL) on murine DC, including the production of inflammatory cytokines, chemokines, DC maturation and antigen-presenting functions. In contrast, hexaacylated GLA was overall more potent on a molar basis than heterogeneous MPL when tested on human DC and peripheral blood mononuclear cells (PBMC). When administered in vivo, GLA enhanced the immunogenicity of co-administered recombinant antigens, producing strong cell-mediated immunity and a qualitative T(H)1 response. We conclude that the GLA adjuvant stimulates and directs innate and adaptive immune responses by inducing DC maturation and the concomitant release of pro-inflammatory cytokines and chemokines associated with immune cell trafficking, activities which have important implications for the development of future vaccine adjuvants.

  7. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant.

    Directory of Open Access Journals (Sweden)

    Rhea N Coler

    Full Text Available Innate immune responses to vaccine adjuvants based on lipopolysaccharide (LPS, a component of gram-negative bacterial cell walls, are driven by Toll-like receptor (TLR 4 and adaptor proteins including MyD88 and TRIF, leading to the production of inflammatory cytokines, type I interferons, and chemokines. We report here on the characterization of a synthetic hexaacylated lipid A derivative, denoted as glucopyranosyl lipid adjuvant (GLA. We assessed the effects of GLA on murine and human dendritic cells (DC by combining microarray, mRNA and protein multiplex assays and flow cytometry analyses. We demonstrate that GLA has multifunctional immunomodulatory activity similar to naturally-derived monophosphory lipid A (MPL on murine DC, including the production of inflammatory cytokines, chemokines, DC maturation and antigen-presenting functions. In contrast, hexaacylated GLA was overall more potent on a molar basis than heterogeneous MPL when tested on human DC and peripheral blood mononuclear cells (PBMC. When administered in vivo, GLA enhanced the immunogenicity of co-administered recombinant antigens, producing strong cell-mediated immunity and a qualitative T(H1 response. We conclude that the GLA adjuvant stimulates and directs innate and adaptive immune responses by inducing DC maturation and the concomitant release of pro-inflammatory cytokines and chemokines associated with immune cell trafficking, activities which have important implications for the development of future vaccine adjuvants.

  8. Postoperative adjuvant chemoradiotherapy in rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Sei Kyung; Kim, Jong Woo; Oh, Do Yeun; Chong, So Young; Shin, Hyun Soo [Bundang CHA General Hospital, Pochon CHA University, Seongnam (Korea, Republic of)

    2006-09-15

    To evaluate the role of postoperative adjuvant chemoradiotherapy in rectal cancer, we retrospectively analyzed the treatment outcome of patients with rectal cancer taken curative surgical resection and postoperative adjuvant chemoradiotherapy. A total 46 patients with AJCC stage II and III carcinoma of rectum were treated with curative surgical resection and postoperative adjuvant chemoradiotherapy. T3 and T4 stage were 38 and 8 patients, respectively. N0, N1, and N2 stage were 12, 16, 18 patients, respectively. Forty patients received bolus infusions of 5-fluorouracil (500 mg/m{sup 2}/day) with leucovorin (20 mg/m{sup 2}/day), every 4 weeks interval for 6 cycles. Oral Uracil/Tegafur on a daily basis for 6 {approx} 12 months was given in 6 patients. Radiotherapy with 45 Gy was delivered to the surgical bed and regional pelvic lymph node area, followed by 5.4 {approx} 9 Gy boost to the surgical bed. The follow up period ranged from 8 to 75 months with a median 35 months. Treatment failure occurred in 17 patients (37%). Locoregional failure occurred in 4 patients (8.7%) and distant failure in 16 patients (34.8%). There was no local failure only. Five year actuarial overall survival (OS) was 51.5% and relapse free survival (RFS) was 58.7%. The OS and RFS were 100%, 100% in stage N0 patients, 53.7%, 47.6% in N1 patients, and 0%, 41.2% in N2 patients ({rho} = 0.012, {rho} = 0.009). The RFS was 55%, 78.5%, and 31.2% in upper, middle, and lower rectal cancer patients, respectively ({rho} = 0.006). Multivariate analysis showed that N stage ({rho} = 0.012) was significant prognostic factor for OS and that N stage ({rho} = 0.001) and location of tumor ({rho} = 0.006) were for RFS. Bowel complications requiring surgery occurred in 3 patients. Postoperative adjuvant chemoradiotherapy was an effective modality for locoregional control of rectal cancer. But further investigations for reducing the distant failure rate are necessary because distant failure rate is still high.

  9. 丹参注射液与丹红注射液辅助治疗急性脑梗死临床疗效的对比研究%Comparative Study for Clinical Effect in the Adjuvant Therapy for Acute Cerebral Infarction between Danshen Injection and Danhong Injection

    Institute of Scientific and Technical Information of China (English)

    卢蓉; 景端

    2016-01-01

    Objective To compare the clinical effect in the adjuvant therapy for acute cerebral infarction between danshen injection and danhong injection. Methods A total of 106 patients with acute cerebral infarction were selected in the People's Hospital of Baoji from February 2015 to February 2016,and they were randomly divided into control group and observation group,each of 53 cases. Based on conventional treatment,patients of A group received extra danhong injection, while patients of B group received extra danshen injection;both groups continuously treated for 2 weeks. Clinical effect,NIHSS score,Barthel index and serum homocysteine level before treatment,after 8 days and 14 days of treatment,and incidence of adverse reactions were compared between the two groups. Results The clinical effect of A group was statistically significantly better than that of B group( P ﹤ 0. 05). No statistically significant differences of NIHSS score or Barthel index was found between the two groups before treatment or after 8 days of treatment(P ﹥ 0. 05);after 14 days of treatment,NIHSS score of A group was statistically significantly lower than that of B group,while Barthel index of A group was statistically significantly higher than that of B group(P ﹤ 0. 05). No statistically significant differences of serum homocysteine level was found between the two groups before treatment(P ﹥ 0. 05),while serum homocysteine level of A group was statistically significantly lower than that of B group after 8 and 14 days of treatment,respectively(P ﹤ 0. 05). No one of the two group occurred any serious adverse reactions during the treatment. Conclusion Danhong injection has better clinical effect than danshen injection in the adjuvant therapy for acute cerebral infarction,can more effectively improve the neurological function and reduce the serum homocysteine level.%目的:比较丹参注射液与丹红注射液辅助治疗急性脑梗死的临床疗效。方法选取2015年2月—2016年2

  10. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy

    DEFF Research Database (Denmark)

    Eggermont, Alexander M M; Chiarion-Sileni, Vanna; Grob, Jean-Jacques;

    2016-01-01

    Background On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had...... undergone complete resection of stage III melanoma. Methods After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months...... patients (1.1%) died owing to immune-related adverse events. Conclusions As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo...

  11. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy

    DEFF Research Database (Denmark)

    Eggermont, Alexander M M; Chiarion-Sileni, Vanna; Grob, Jean-Jacques

    2016-01-01

    Background On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had...... undergone complete resection of stage III melanoma. Methods After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months...... patients (1.1%) died owing to immune-related adverse events. Conclusions As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo...

  12. Lactic acid bacteria as adjuvants for sublingual allergy vaccines.

    Science.gov (United States)

    Van Overtvelt, Laurence; Moussu, Helene; Horiot, Stéphane; Samson, Sandrine; Lombardi, Vincent; Mascarell, Laurent; van de Moer, Ariane; Bourdet-Sicard, Raphaëlle; Moingeon, Philippe

    2010-04-01

    We compared immunomodulatory properties of 11 strains of lactic acid bacteria as well as their capacity to enhance sublingual immunotherapy efficacy in a murine asthma model. Two types of bacterial strains were identified, including: (i) potent inducers of IL-12p70 and IL-10 in dendritic cells, supporting IFN-gamma and IL-10 production in CD4+ T cells such as Lactobacillus helveticus; (ii) pure Th1 inducers such as L. casei. Sublingual administration in ovalbumin-sensitized mice of L. helveticus, but not L. casei, reduced airways hyperresponsiveness, bronchial inflammation and proliferation of specific T cells in cervical lymph nodes. Thus, probiotics acting as a Th1/possibly Treg, but not Th1 adjuvant, potentiate tolerance induction via the sublingual route.

  13. Caffeine as an opioid analgesic adjuvant in fibromyalgia.

    Science.gov (United States)

    Scott, J Ryan; Hassett, Afton L; Brummett, Chad M; Harris, Richard E; Clauw, Daniel J; Harte, Steven E

    2017-01-01

    Caffeine's properties as an analgesic adjuvant with nonsteroidal anti-inflammatory drugs/acetaminophen are well documented. However, little clinical research has explored caffeine's effects on opioid analgesia. This study assessed the effects of caffeine consumption on pain and other symptoms in opioid-using and nonusing chronic pain patients meeting the survey criteria for fibromyalgia. Patients presenting to a university-based pain clinic completed validated self-report questionnaires assessing symptoms. Patients (N=962) meeting the fibromyalgia survey criteria were stratified by opioid use and further split into groups based on caffeine amount consumed per day (no caffeine, or low, moderate, high caffeine). Analysis of covariance with Dunnett's post hoc testing compared pain and symptom severity between the no caffeine group and the caffeine consuming groups. In opioid users, caffeine consumption had modest but significant effects on pain, catastrophizing, and physical function. Lower levels of pain interference were associated with low and moderate caffeine use compared to no caffeine intake. Lower pain catastrophizing and higher physical function were observed in all caffeine dose groups, relative to the no caffeine group. Lower pain severity and depression were observed only in the moderate caffeine group. In opioid nonusers, low caffeine intake was associated with higher physical function; however, no other significant effects were observed. Caffeine consumption was associated with decreased pain and symptom severity in opioid users, but not in opioid nonusers, indicating caffeine may act as an opioid adjuvant in fibromyalgia-like chronic pain patients. These data suggest that caffeine consumption concomitant with opioid analgesics could provide therapeutic benefits not seen with opioids or caffeine alone.

  14. Vaccination with self-adjuvanted protein nanoparticles provides protection against lethal influenza challenge.

    Science.gov (United States)

    Karch, Christopher P; Li, Jianping; Kulangara, Caroline; Paulillo, Sara M; Raman, Senthil K; Emadi, Sharareh; Tan, Anmin; Helal, Zeinab H; Fan, Qing; Khan, Mazhar I; Burkhard, Peter

    2017-01-01

    Current influenza vaccines should be improved by the addition of universal influenza vaccine antigens in order to protect against multiple virus strains. We used our self-assembling protein nanoparticles (SAPNs) to display the two conserved influenza antigens M2e and Helix C in their native oligomerization states. To further improve the immunogenicity of the SAPNs, we designed and incorporated the TLR5 agonist flagellin into the SAPNs to generate self-adjuvanted SAPNs. We demonstrate that addition of flagellin does not affect the ability of SAPNs to self-assemble and that they are able to stimulate TLR5 in a dose-dependent manner. Chickens vaccinated with the self-adjuvanted SAPNs induce significantly higher levels of antibodies than those with unadjuvanted SAPNs and show higher cross-neutralizing activity compared to a commercial inactivated virus vaccine. Upon immunization with self-adjuvanted SAPNs, mice were completely protected against a lethal challenge. Thus, we have generated a self-adjuvanted SAPN with a great potential as a universal influenza vaccine.

  15. Adherence to endocrine therapy in breast cancer adjuvant and prevention settings.

    Science.gov (United States)

    Chlebowski, Rowan T; Kim, Jisang; Haque, Reina

    2014-04-01

    Adherence to oral endocrine therapy in adjuvant breast cancer settings is a substantial clinical problem. To provide current perspective on adherence to oral endocrine therapies, a comprehensive literature review was conducted. In adjuvant trials, endocrine therapy adherence is relatively high with greater adherence for aromatase inhibitors compared with tamoxifen. In contrast, adherence to adjuvant therapy in clinical practice is relatively poor, with only about 50% of women successfully completing 5-year therapy. Importantly, good adherence (>80% use) has been associated with lower recurrence risk. Endocrine therapy adherence in primary breast cancer prevention trials parallels that seen in adjuvant trials. Factors associated with nonadherence include low recurrence risk perception, side effects, age extremes, medication cost, suboptimal patient-physician communication, and lack of social support. Few prospective studies have evaluated interventions designed to improve adherence. Interventions currently proposed reflect inferences from clinical trial procedures in which clinical contacts are commonly greater than in usual practice settings. In conclusion, for optimal breast cancer outcome, adherence to endocrine therapy must improve. Although general recommendations likely to improve adherence can be made based on clinical trial results and preliminary prospective trial findings, research specifically targeting this issue is needed to establish effective intervention strategies.

  16. Dose-dense and sequential strategies in adjuvant breast cancer therapy.

    Science.gov (United States)

    Untch, M; Von Koch, F; Crohns, C; Sobotta, K; Kahlert, S; Konecny, G; Hepp, H

    2001-05-01

    Several attempts have been made to improve the survival rates of breast cancer patients. The benefit of adjuvant chemotherapy was clearly shown, but the absolute difference of 2% to 11% in overall survival, depending on the patient group, is disappointingly small. In particular, high-risk patients, such as those with > or = 10 involved lymph nodes, extracapsular spread, or vascular invasion, still have an excessive risk of recurrence even after standard adjuvant chemotherapy. To increase the survival rates after adjuvant therapy, new chemotherapeutic agents and new strategies of application are currently being evaluated in clinical trials. Chemotherapy with cyclophosphamide (Cytoxan, Neosar), methotrexate, and fluorouracil (CMF) seems to be safe and effective in patients with breast cancer. In addition, in metastatic patients, dose-intensified chemotherapy is being investigated. The introduction of epirubicin (Ellence), an agent less cardiotoxic and equally active compared to doxorubicin, enabled the escalation of anthracyclines in adjuvant therapy without serious cardiotoxic effects. The combination of dose-intensified chemotherapy and sequential application in the treatment of breast cancer is reviewed.

  17. Evaluation of immune response elicited by inulin as an adjuvant with filarial antigens in mice model.

    Science.gov (United States)

    Mahalakshmi, N; Aparnaa, R; Kaliraj, P

    2014-10-01

    Filariasis caused by infectious parasitic nematodes has been identified as the second leading source of permanent and long-term disability in Sub-Saharan Africa, Asia and Latin America. Several vaccine candidates were identified from infective third-stage larvae (L3) which involves in the critical transition from arthropod to human. Hitherto studies of these antigens in combination with alum adjuvant have shown to elicit its characteristic Th2 responses. Inulin is a safe, non-toxic adjuvant that principally stimulates the innate immune response through the alternative complement pathway. In the present study, the immune response elicited by inulin and alum as adjuvants were compared with filarial antigens from different aetiological agents: secreted larval acidic protein 1 (SLAP1) from Onchocerca volvulus and venom allergen homologue (VAH) from Brugia malayi as single or as cocktail vaccines in mice model. The study revealed that inulin can induce better humoral response against these antigens than alum adjuvant. Antibody isotyping disclosed inulin's ability to elevate the levels of IgG2a and IgG3 antibodies which mediates in complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC), respectively, in mice. Splenocyte analysis showed that T cells prestimulated with inulin have higher stimulation index (P inulin formulation had induced higher cytotoxicity with filarial antigens (as single P inulin to deplete the levels of Treg and brought a balance in Th1/Th2 arms against filarial antigens in mice.

  18. The importance of adjuvant chemotherapy and pelvic radiotherapy in high-risk early stage endometrial carcinoma.

    Science.gov (United States)

    Jutzi, Leah; Hoskins, Paul; Lim, Peter; Aquino-Parsons, Christina; Tinker, Anna; Kwon, Janice S

    2013-12-01

    To determine the impact of a policy change in which women with high-risk early stage endometrioid endometrial cancer (EEC) received adjuvant chemoradiotherapy. This is a population-based retrospective cohort study of British Columbia Cancer Registry patients diagnosed from 2008 to 2012 with high-risk early stage EEC, who received adjuvant chemoradiotherapy after primary surgery. High-risk early stage was defined as the presence of two or more high-risk uterine factors: grade 3 tumor, more than 50% myometrial invasion, and/or cervical stromal involvement. Adjuvant therapy consisted of 3 or 4 cycles of carboplatin and paclitaxel chemotherapy, followed by pelvic radiotherapy. Sites and rate of recurrence were compared to a historical cohort diagnosed from 2005 to 2008 in which none of the patients received adjuvant chemoradiotherapy. Five-year progression-free and overall survival rates were calculated. The study includes 55 patients. All patients except for 2 received at least 3 cycles of chemotherapy. All patients received pelvic radiotherapy except for 2 who received brachytherapy only. Median follow-up was 27 months (7-56 months). Four patients (7.3%) recurred, including three with distant recurrence only and one with both a pelvic and paraaortic nodal recurrence. The historical cohort had a 29.4% recurrence rate, and therefore the hazard ratio for recurrence was 0.27 (95% CI 0.02-4.11). Five-year progression-free and overall survival rates were 88.6% and 97.3%, respectively. Patients with high-risk early stage endometrial carcinoma treated with adjuvant chemoradiotherapy have a low rate of recurrence compared to those not receiving such therapy. © 2013.

  19. Changes in adjuvant therapy utilization in stage I seminoma: are they enough to prevent overtreatment?

    Science.gov (United States)

    Kohut, Robert M; Minnillo, Brian J; Kypriotakis, Georgios; Abouassaly, Robert; Zhu, Hui

    2014-12-01

    To determine if utilization of surveillance or adjuvant chemotherapy has increased compared with that of adjuvant radiotherapy (ART) in clinical stage I seminoma (CSIS) and to estimate the impact of this utilization trend on secondary malignancies. The National Cancer Data Base, a web-based data analysis tool was examined for first-course adjuvant therapy management in CSIS from 2000 to 2008. We assessed the utilization in academic vs community practice settings and changes in tumor stage. We also estimated the number of secondary malignancies based on the change in practice. There were 52,672 patients of testicular cancer diagnosed. Of those, 28,974 (55.0%) patients had seminoma with 22,210 (84.2%) patients classified as CSIS. Overall, 14,005 (65.4%), 6430 (30.1%), and 951 (4.4%) patients received ART, surveillance, and adjuvant chemotherapy (AC), respectively. In 2000, most patients received ART (71.7%), followed by surveillance (26.5%), and AC (1.9%). In 2008, the majority of patients still received ART (47.7%) but surveillance (39.6%) and AC (12.6%) totaled a larger proportion. We calculated that this ART utilization rate would lead to an additional 372 solid tumor cases per year, 40 years later, whereas the current surveillance rate would lead to 34 cases of secondary malignancy annually in the United States. ART was the leading adjuvant management strategy for CSIS, but its share drastically decreased with a concomitant increase in surveillance and AC, particularly after 2004. These trends were similar in both academic and community settings. The current level of ART, although decreasing, may nevertheless lead to additional cases of solid cancer comparable with testicular cancer deaths. Published by Elsevier Inc.

  20. Vaccine priming is restricted to draining lymph nodes and controlled by adjuvant-mediated antigen uptake.

    Science.gov (United States)

    Liang, Frank; Lindgren, Gustaf; Sandgren, Kerrie J; Thompson, Elizabeth A; Francica, Joseph R; Seubert, Anja; De Gregorio, Ennio; Barnett, Susan; O'Hagan, Derek T; Sullivan, Nancy J; Koup, Richard A; Seder, Robert A; Loré, Karin

    2017-06-07

    The innate immune mechanisms by which adjuvants enhance the potency and protection of vaccine-induced adaptive immunity are largely unknown. We introduce a model to delineate the steps of how adjuvant-driven innate immune activation leads to priming of vaccine responses using rhesus macaques. Fluorescently labeled HIV-1 envelope glycoprotein (Env) was administered together with the conventional aluminum salt (alum) adjuvant. This was compared to Env given with alum with preabsorbed Toll-like receptor 7 (TLR7) ligand (alum-TLR7) or the emulsion MF59 because they show superiority over alum for qualitatively and quantitatively improved vaccine responses. All adjuvants induced rapid and robust immune cell infiltration to the injection site in the muscle. This resulted in substantial uptake of Env by neutrophils, monocytes, and myeloid and plasmacytoid dendritic cells (DCs) and migration exclusively to the vaccine-draining lymph nodes (LNs). Although less proficient than monocytes and DCs, neutrophils were capable of presenting Env to memory CD4(+) T cells. MF59 and alum-TLR7 showed more pronounced cell activation and overall higher numbers of Env(+) cells compared to alum. This resulted in priming of higher numbers of Env-specific CD4(+) T cells in the vaccine-draining LNs, which directly correlated with increased T follicular helper cell differentiation and germinal center formation. Thus, strong innate immune activation promoting efficient vaccine antigen delivery to infiltrating antigen-presenting cells in draining LNs is an important mechanism by which superior adjuvants enhance vaccine responses. Copyright © 2017, American Association for the Advancement of Science.

  1. 21 CFR 178.3010 - Adjuvant substances used in the manufacture of foamed plastics.

    Science.gov (United States)

    2010-04-01

    ...: ADJUVANTS, PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants and Production Aids § 178.3010 Adjuvant... weight of finished foamed polyethylene. 1,1-Difluoroethane (CAS Reg. No. 75-37-6) For use as a blowing...

  2. Human Phase 1 trial of low-dose inactivated seasonal influenza vaccine formulated with Advax™ delta inulin adjuvant.

    Science.gov (United States)

    Gordon, David L; Sajkov, Dimitar; Honda-Okubo, Yoshikazu; Wilks, Samuel H; Aban, Malet; Barr, Ian G; Petrovsky, Nikolai

    2016-07-19

    Influenza vaccines are usually non-adjuvanted but addition of adjuvant may improve immunogenicity and permit dose-sparing, critical for vaccine supply in the event of an influenza pandemic. The aim of this first-in-man study was to determine the effect of delta inulin adjuvant on the safety and immunogenicity of a reduced dose seasonal influenza vaccine. Healthy male and female adults aged 18-65years were recruited to participate in a randomized controlled study to compare the safety, tolerability and immunogenicity of a reduced-dose 2007 Southern Hemisphere trivalent inactivated influenza vaccine formulated with Advax™ delta inulin adjuvant (LTIV+Adj) when compared to a full-dose of the standard TIV vaccine which does not contain an adjuvant. LTIV+Adj provided equivalent immunogenicity to standard TIV vaccine as assessed by hemagglutination inhibition (HI) assays against each vaccine strain as well as against a number of heterosubtypic strains. HI responses were sustained at 3months post-immunisation in both groups. Antibody landscapes against a large panel of H3N2 influenza viruses showed distinct age effects whereby subjects over 40years old had a bimodal baseline HI distribution pattern, with the highest HI titers against the very oldest H3N2 isolates and with a second HI peak against influenza isolates from the last 5-10years. By contrast, subjects >40years had a unimodal baseline HI distribution with peak recognition of H3N2 isolates from approximately 20years ago. The reduced dose TIV vaccine containing Advax adjuvant was well tolerated and no safety issues were identified. Hence, delta inulin may be a useful adjuvant for use in seasonal or pandemic influenza vaccines. Australia New Zealand Clinical Trial Registry: ACTRN12607000599471.

  3. The mode of action of immunological adjuvants.

    Science.gov (United States)

    Allison, A C

    1998-01-01

    Adjuvants augment immune responses to antigens and influence the balance between cell-mediated and humoral responses, as well as the isotypes of antibodies formed. New adjuvant formulations include antigen-carrying vehicles and small molecules with immunomodulating activity. Widely used two-phase vehicles comprise liposomes and microfluidized squalene or squalane emulsions. These are believed to target antigens to antigen-presenting cells, including dendritic cells (DC), follicular dendritic cells (FDC) and B-lymphocytes. Activation of complement generates C3d, which binds CR2 (CD21) on FDC and B-lymphocytes, thereby stimulating the proliferation of the latter and the generation of B-memory. Targeting of antigens to DC may favour cell-mediated immunity. Immunomodulating agents induce the production of cytokine cascades. In a primary cascade at injection sites TNF-alpha, GM-CSF and IL-1 are produced. TNF-alpha promotes migration of DC to lymphoid tissues, while GM-CSF and IL-1 accelerate the maturation of DC into efficient antigen-presenting cells for T-lymphocytes. In a secondary cytokine cascade in draining lymph nodes, DC produce IL-12, which induces Th1 responses with the production of IFN-gamma. The cytokines elicit cell-mediated immune responses and the formation of antibodies of protective isotypes, such as IgG2a in the mouse and IgG1 in humans. Antibodies of these isotypes activate complement and collaborate with antibody-dependent effector cells in protective immune responses.

  4. The role of postoperative adjuvant radiotherapy in resected esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chang Geol; Kim, Choong Bae; Chung, Kyung Young; Lee, Doo Yun; Seong Jin Sil; Kim, Gwi Eon; Suh, Chang Ok [Yonsei University College of Medicine, Yonsei Cancer Center, Seoul (Korea, Republic of)

    2002-12-15

    A retrospective study was performed to evaluate whether postoperative adjuvant radiotherapy can improve survival and decrease recurrence as compared with surgery alone in resected esophageal cancer. From Jan. 1985 to Dec. 1993, among 94 esophageal cancer patients treated with surgery, fifty-one patients were included in this study. Transthoracic esophagectomy was performed in 35 patients and transhiatal esophagectomy in 16. Postoperative adjuvant radiotherapy was performed 4 weeks after surgery in 26 among 38 patients in stage II and III. A total dose of 30 {approx} 60 Gy in 1.8 Gy daily fraction, median 54 Gy over 6 weeks, was delivered in the mediastinum + both supraclavicular lymph nodes or celiac lymph nodes according to the tumor location. Forty-seven patients (92%) had squamous histology. The median follow-up period was 38 months. The overall 2-year and 5-year survival and median survival were 56.4%, 36.8% and 45 months. Two-year and 5-year survival and median survival by stage were 92%, 60.3% for stage I, 63%, 42% and 51 months for stage II and 34%, 23% and 19 months for stage III ({rho} = 0.04). For stage II and III patients, 5-year survival and median survival were 22.8%. 45 months for the surgery alone group and 37.8%, 22 months for the postoperative RT group ({rho} = 0.89). For stage III patients, 2-year survival and median survival were 0%, 11 months for the surgery alone group and 36.5%, 20 months for the postoperative RT group ({rho} = 0.14). Local and distant failure rates for stage II and III were 50%, 16% for the surgery alone and 39%, 31% for the postoperative RT group. For N1 patients, local failure rate was 71% for the surgery alone group and 37% for the postoperative RT group ({rho} = 0.19). Among 10 local failures in the postoperative RT group, in-field failures were 2, marginal failures 1, out-field 5 and anastomotic site failures 2. There were no statistically significant differences in either the overall survival or the patterns of failure

  5. Silica nanoparticles as the adjuvant for the immunisation of mice using hepatitis B core virus-like particles.

    Directory of Open Access Journals (Sweden)

    Dace Skrastina

    Full Text Available Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10-20 nm with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs formed by recombinant full-length Hepatitis B virus core (HBc protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component.

  6. Protein antigen adsorption to the DDA/TDB liposomal adjuvant

    DEFF Research Database (Denmark)

    Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber;

    2013-01-01

    Understanding the nature of adjuvant-antigen interactions is important for the future design of efficient and safe subunit vaccines, but remains an analytical challenge. We studied the interactions between three model protein antigens and the clinically tested cationic liposomal adjuvant composed...

  7. Comparative study on the clinical effect of minocycline hydrochloride ointment and lodine glycerin as adju-vant therapy for pericoronitis with parulis%米诺环素软膏与碘甘油辅助治疗第三磨牙冠周炎伴牙龈脓肿的效果比较

    Institute of Scientific and Technical Information of China (English)

    葛光华; 李晋芳; 江小平; 吴琼

    2016-01-01

    目的:比较盐酸米诺环素软膏与碘甘油辅助治疗第三磨牙冠周炎伴牙龈脓肿的临床效果。方法164例患第三磨牙冠周炎伴牙龈脓肿的青年大学生患者,随机分为2组,每组82例,2组均行牙龈脓肿切开排脓、冠周冲洗上药、口服替硝唑、头孢拉啶和复方硼砂含漱液含漱等综合治疗,试验组冠周上质量分数2%的盐酸米诺环素软膏,每3天1次;对照组冠周上质量分数1%的碘甘油,每天1次。治疗3d后复诊,对比2组的疗效。结果试验组总有效率为93.9%,对照组为78.0%,差异有统计学意义(χ2=8.546,P=0.003)。2组均未发生药物不良反应。结论盐酸米诺环素软膏辅助治疗第三磨牙冠周炎伴牙龈脓肿可收到良好的临床效果。%Objective To compare the clinical effects of minocycline hydrochloride ointment (Periocline) and lo⁃dine glycerin as adjuvant therapy for pericoronitis with parulis. Methods 164 college students suffering from pericoro⁃nitis with parulis were divided into 2 groups randomly: observation group (82 cases) and control group (82 cases). All cases were treated with incision and drainage of the parulis, and then pericoronal rinsing. What's more, tinidazole and cefradine plus compound borax gargle mouthwash were given to them. 2% Periocline was filled into the periodontal pocket for the observation group (q3d) while 1% lodine glycerin was filled into the periodontal pocket for the control group (qd). Clinical effects of the two groups were observed and compared 3 days later. Results The effective rate of observation group (93.9%) was higher than that of control group (78.0%) with statistically significance (χ2=8.546, P=0.003). No drug adverse reaction occured. Conclusion It shows good effects when Periocline is applied as an adju⁃vant therapy for pericoronitis with parulis.

  8. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    OpenAIRE

    Samantha Sayers; Guerlain Ulysse; Zuoshuang Xiang; Yongqun He

    2012-01-01

    Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bi...

  9. Immune adjuvant activity of the olive, soybean and corn oils

    Directory of Open Access Journals (Sweden)

    Ana Claudia Marinho da Silva

    2016-08-01

    Full Text Available In the last half of the century, a large amount of substances has been used as immune adjuvant. The immune adjuvant effect of olive, soybean and corn oils in Swiss mice immunized with ovalbumin (OVA plus aluminum hydroxide or emulsified in Marcol, soybean, olive or corn oils was evaluated through the OVA-specific antibodies determined by ELISA and Passive Cutaneous Anaphylaxis. In this work the comparison of the intensity of the immune response was established by the Bayesian analysis. The adjuvant effect of the vegetable oils was shown to be more effective than aluminium hydroxide. Regarding to OVA-specific IgE synthesis, olive oil had the slowest adjuvant effect of the three vegetable oils. Accordingly, olive oil was the most convenient among the vegetable oils to be used as immune adjuvant, since it stimulated a higher production of OVA-specific Ig and lower levels of anti-OVA IgE.

  10. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    Directory of Open Access Journals (Sweden)

    Samantha Sayers

    2012-01-01

    Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.

  11. Underuse of Breast Cancer Adjuvant Treatment: Patient Knowledge, Beliefs, and Medical Mistrust

    Science.gov (United States)

    Bickell, Nina A.; Weidmann, Jessica; Fei, Kezhen; Lin, Jenny J.; Leventhal, Howard

    2009-01-01

    Purpose Little is known about why women with breast cancer who have surgery do not receive proven effective postsurgical adjuvant treatments. Methods We surveyed 258 women who recently underwent surgical treatment at six New York City hospitals for early-stage breast cancer about their care, knowledge, and beliefs about breast cancer and its treatment. As per national guidelines, all women should have received adjuvant treatment. Adjuvant treatment data were obtained from inpatient and outpatient charts. Factor analysis was used to create scales scored to 100 of treatment beliefs and knowledge, medical mistrust, and physician communication about treatment. Bivariate and multivariate analyses assessed differences between treated and untreated women. Results Compared with treated women, untreated women were less likely to know that adjuvant therapies increase survival (on a 100-point scale; 66 v 75; P < .0001), had greater mistrust (64 v 53; P = .001), and had less self-efficacy (92 v 97; P < .05); physician communication about treatment did not affect patient knowledge of treatment benefits (r = 0.8; P = .21). Multivariate analysis found that untreated women were more likely to be 70 years or older (adjusted relative risk [aRR], 1.11; 95% CI, 1.00 to 1.13), to have comorbidities (aRR, 1.10; 95% CI, 1.04 to 1.12), and to express mistrust in the medical delivery system (aRR, 1.003; 95% CI, 1.00 to 1.007), even though they were more likely to believe adjuvant treatments were beneficial (aRR, 0.99; 95% CI, 0.98 to 0.99; model c, 0.84; P ≤ .0001). Conclusion Patient knowledge and beliefs about treatment and medical mistrust are mutable factors associated with underuse of effective adjuvant therapies. Physicians may improve cancer care by ensuring that discussions about adjuvant therapy include a clear presentation of the benefits, not just the risks of treatment, and by addressing patient trust in and concerns about the medical system. PMID:19770368

  12. The benefit of adjuvant chemotherapy combined with postoperative radiotherapy for endometrial cancer: a meta-analysis.

    Science.gov (United States)

    Park, Hyun Jong; Nam, Eun Ji; Kim, Sunghoon; Kim, Yong Bae; Kim, Young Tae

    2013-09-01

    The objective of our study was to determine whether adjuvant chemotherapy combined with postoperative radiotherapy would have benefits for the disease-free survival and overall survival in patients with high-risk endometrial cancer. Electronic searches for studies of adjuvant chemotherapy combined with postoperative radiotherapy in endometrial cancer patients between March 1971 and March 2012 were made on MEDLINE, SCOPUS, and the Cochrane library. Articles with more than 4 stars on the Newcastle-Ottawa scale or a score of more than 4 on the modified Jadad scale were included. A meta-analysis was performed, and pooled hazard ratios (HR) of progression-free survival (PFS) and overall survival (OS) between patients whose adjuvant chemotherapy was combined with radiotherapy (the CTx+RTx group) and patients with adjuvant radiotherapy only (the RTx group) were derived from the fixed effect model or random effect model. Three observational studies and 3 randomized clinical trials (RCTs) were included in the final analysis. Subgroup analysis for FIGO stage showed that the CTx+RTx group had a more significant survival benefit compared to that of the RTx group in advanced stage endometrial cancer (OS HR 0.53, 95% CI 0.36-0.80; PFS HR 0.54, 95% CI 0.37-0.77), but no significant benefit in early stage endometrial cancer (OS HR 0.96, 95% CI 0.70-1.32; PFS HR 1.00, 95% CI 0.39-2.58). This meta-analysis suggests that adjuvant chemotherapy combined with postoperative radiotherapy could probably reduce disease progression and overall death in patients with advanced-stage disease. In order to examine whether the multimodal treatment has benefit in high-risk endometrial cancer, we need further large-scale RCTs. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    Directory of Open Access Journals (Sweden)

    Signe Tandrup Schmidt

    2016-03-01

    Full Text Available The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI. Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs, which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the

  14. Surveillance versus adjuvant radiotherapy for patients with high-risk stage I seminoma.

    Science.gov (United States)

    Mortensen, Mette S; Bandak, Mikkel; Kier, Maria G G; Lauritsen, Jakob; Agerbaek, Mads; Holm, Niels V; von der Maase, Hans; Daugaard, Gedske

    2017-04-01

    The optimal treatment strategy for patients with clinical stage I (CS-1) seminoma is controversial. The objective of the current study was to evaluate the outcomes for patients considered to be at high risk of disease recurrence with a tumor size ≥6 cm. Patients were treated with either adjuvant radiotherapy (RT) or followed with surveillance. From the Danish Testicular Cancer database, the authors identified 473 patients with CS-1 seminoma with a tumor size ≥6 cm. Of these, 254 patients underwent adjuvant RT and 219 were followed with surveillance. Cumulative incidence function was applied to estimate the risk of disease recurrence, risk of second malignant neoplasm, and risk of receiving >1 line of treatment. Survival of the 2 groups was compared with the log-rank test and Cox model including age at diagnosis. No significant differences were found with regard to overall survival or risk of a second malignant neoplasm. Patients undergoing adjuvant RT received more treatments per patient than patients followed with surveillance, but there was no significant difference noted with regard to the risk of receiving >1 line of treatment. The 10-year cumulative incidence of disease recurrence was 32% versus 2.8%, respectively, for patients followed with surveillance and adjuvant RT. In patients followed with surveillance who developed disease recurrence, there was a high incidence of second recurrences after RT. The 10-year overall survival was found to be similar irrespective of primary treatment. Adjuvant RT was found to effectively reduce the rate of disease recurrence but resulted in the overtreatment of approximately two-thirds of the patients. The high incidence of second disease recurrences after RT in the patients followed with surveillance needs be addressed in future studies. Cancer 2017;123:1212-1218. © 2016 American Cancer Society. © 2016 American Cancer Society.

  15. Retroperitoneal liposarcoma; The role of adjuvant radiation therapy and the prognostic factors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hong Seok; Yu, Jeong Il; Lim, Do Hoon; Kim, Sung Joo [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2016-09-15

    To evaluate the benefit of adjuvant radiation therapy (RT) for retroperitoneal liposarcoma (RPLS) following gross tumor removal. We reviewed 77 patients with primary RPLS surgically treated between January 2000 and December 2013. Cases with gross residual disease were excluded. Tumor grade was evaluated according to the French Federation of Cancer Centers Sarcoma Group (FNCLCC) system. Adjuvant RT was delivered to 32 patients (42%) using external beam RT alone. Median follow-up time was 36 months (range, 5 to 169). Among 77 patients, 33 (43%) presented with well-differentiated, 31 (40%) with de-differentiated, 8 (10%) with myxoid/round and 4 (5%) with pleomorphic morphology. The RT group included less well-differentiated subtype than surgery group (28% vs. 53%). During follow up, 34 patients (44%) showed local recurrence. Local recurrence rate was lower in the RT group (38%) compared to the surgery group (49%). The 3-year local control rate (LC) was 55.6%, and the 3-year overall survival (OS) was 82.1%. Tumor histology and FNCLCC grade were significantly associated with local recurrence. There was no statistical significance of adding adjuvant RT in LC (p = 0.312). However, patients with tumor histology other than well-differentiated subtype showed marginally decreased local recurrence rate after adjuvant RT (3-year LC, RT 43.9% vs. no RT 35.3%; p = 0.087). RPLS patients receiving RT experienced less local recurrence. We suggest that the addition of adjuvant RT may be related to improvement of LCs, especially in patients with non-favorable histologic subtypes.

  16. Tolerability and toxicity of adjuvant cisplatin and gemcitabine for treating non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    YANG Fan; LI Xiao; CHEN Ke-zhong; JIANG Guan-chao; WANG Jun

    2013-01-01

    Background The combination of cisplatin and vinorelbine is an evidence-supported regimen for adjuvant chemotherapy for treating non-small cell lung cancer (NSCLC).But this doublet has considerable toxicity and unfavorable tolerability,and results in poor compliance.The cisplatin and gemcitabine regimen is one of the most active and well-tolerated regimens against advanced NSCLC,but its toxicity and tolerability has not been adequately evaluated in the adjuvant setting.Methods From a lung cancer database we retrospectively reviewed NSCLC patients receiving adjuvant chemotherapy of cisplatin (75 mg/m2) and gemcitabine (1250 mg/m2) between January 2005 and December 2011.Postoperative demographics,compliance to adjuvant therapy and toxicity were retrieved from medical records.Results A total of 132 patients met the criteria and were included in the study,96 were male (72.7%) and 36 were female (27.3%).Median age was 60.5 years old,range 29-75 years,and 41.7% of patients were ≥65 years old.Overall,68.2%patients received all four planned cycles,and the cumulative dose delivered for gemcitabine was 8333 mg (83.3% of the planned dose) and cisplatin 248 mg (82.7% of the planned dose).There were no treatment-related deaths.Grade 3/4neutropenia developed in 47 patients (35.6%) and was the predominant hematologic toxicity.Common grade 3/4 nonhematologic toxicities were nausea/vomiting (22.0%),infection (12.3%),and febrile neutropenia (11.4%).Conclusion Cisplatin and gemcitabine are feasible for use in the adjuvant setting with a favorable toxicity profile and superior tolerability compared with published data on cisplatin and vinorelbine.

  17. Parenteral adjuvant effects of an enterotoxigenic Escherichia coli (ETEC natural heat-labile toxin variant

    Directory of Open Access Journals (Sweden)

    Catarina Joelma Magalhães Braga

    2014-01-01

    Full Text Available Native type I heat-labile toxins (LTs produced by enterotoxigenic Escherichia coli (ETEC strains exert strong adjuvant effects on both antibody and T cell responses to soluble and particulate antigens following co-administration via mucosal routes. However, inherent enterotoxicity and neurotoxicity (following intranasal delivery had reduced the interest in the use of these toxins as mucosal adjuvants. LTs can also behave as powerful and safe adjuvants following delivery via parenteral routes, particularly for activation of cytotoxic lymphocytes. In the present study, we evaluated the adjuvant effects of a new natural LT polymorphic form (LT2, after delivery via intradermal (i.d. and subcutaneous (s.c. routes, with regard to both antibody and T cell responses. A recombinant HIV-1 p24 protein was employed as a model antigen for determination of antigen-specific immune responses while the reference LT (LT1, produced by the ETEC H10407 strain, and a non-toxigenic LT form (LTK63 were employed as previously characterized LT types. LT-treated mice submitted to a four dose-base immunization regimen elicited similar p24-specific serum IgG responses and CD4+ T cell activation. Nonetheless, mice immunised with LT1 or LT2 induced higher numbers of antigen-specific CD8+ T cells and in vivo cytotoxic responses compared to mice immunised with the non-toxic LT derivative. These effects were correlated with stronger activation of local dendritic cell populations. In addition, mice immunized with LT1 and LT2, but not with LTK63, via s.c. or i.d. routes developed local inflammatory reactions. Altogether, the present results confirmed that the two most prevalent natural polymorphic LT variants (LT1 or LT2 display similar and strong adjuvant effects for subunit vaccines administered via i.d. or s.c. routes.

  18. Laparoscopy mitigates adverse oncological effects of delayed adjuvant chemotherapy for colon cancer.

    Science.gov (United States)

    Gantt, Gerald A; Ashburn, Jean; Kiran, Ravi P; Khorana, Alok A; Kalady, Matthew F

    2015-02-01

    Delaying initiation of adjuvant chemotherapy more than 8 weeks after surgical resection for colorectal cancer adversely affects overall patient survival. The effect of a laparoscopic surgical approach on initiation of chemotherapy has not been studied. The goal of this study was to determine if a laparoscopic approach to colon cancer resection affects the timing of adjuvant chemotherapy and outcomes. Patients who underwent curative surgery for stage II or III colon cancer and received adjuvant chemotherapy between 2003 and 2010 were identified from a prospectively maintained database. Patients were categorized according to surgical approach: open or laparoscopic. Patient demographics, clinicopathologic variables, postoperative complications, time from surgery to initiation of chemotherapy, and long-term oncologic outcomes were compared. Age, gender, ASA class, BMI, tumor stage, and postoperative complications were similar for laparoscopic and open cases, while length of stay was 2 days shorter for laparoscopic cases (5.4 vs 7.6 days, p < 0.01). The proportion of patients who received adjuvant chemotherapy more than 8 weeks after surgery did not differ between the groups (35.6 % open vs 38.7 % laparoscopic, p = 0.77). In the open group, delay in chemotherapy after surgery was associated with decreased disease-free and overall survival (p = 0.01, 0.01, respectively). However, delay in chemotherapy more than 8 weeks did not affect disease-free or overall survival in the laparoscopy group (p = 0.93, 0.51, respectively). The benefits of quicker recovery after laparoscopic surgery did not translate into earlier initiation of adjuvant chemotherapy in this retrospective study. However, a laparoscopic approach negated the inferior oncologic outcomes of patients who received delayed initiation of chemotherapy.

  19. Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant.

    Science.gov (United States)

    Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita; Merkel, Tod J

    2014-04-01

    Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy.

  20. Advax-Adjuvanted Recombinant Protective Antigen Provides Protection against Inhalational Anthrax That Is Further Enhanced by Addition of Murabutide Adjuvant

    Science.gov (United States)

    Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita

    2014-01-01

    Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy. PMID:24554695

  1. Construction and preclinical evaluation of mmCT, a novel mutant cholera toxin adjuvant that can be efficiently produced in genetically manipulated Vibrio cholerae.

    Science.gov (United States)

    Lebens, Michael; Terrinoni, Manuela; Karlsson, Stefan L; Larena, Maximilian; Gustafsson-Hedberg, Tobias; Källgård, Susanne; Nygren, Erik; Holmgren, Jan

    2016-04-19

    There is an urgent need for new adjuvants that are effective with mucosally administered vaccines. Cholera toxin (CT) is the most powerful known mucosal adjuvant but is much too toxic for human use. In an effort to develop a useful mucosal adjuvant we have generated a novel non-toxic mutant CT molecule that retains much of the adjuvant activity of native CT. This was achieved by making the enzymatically active A subunit (CTA) recalcitrant to the site-specific proteolytic cleavage ("nicking") required for toxicity, which was found to require mutations not only in the two residues rendering the molecule resistant to trypsin but also in neighboring sites protecting against cleavage by Vibrio cholerae proteases. This multiple-mutated CT (mmCT) adjuvant protein could be efficiently produced in and purified from the extracellular medium of CT-deleted V. cholerae. The mmCT completely lacked detectable enterotoxicity in an infant mouse model and had >1000-fold reduced cAMP inducing activity compared to native CT in a sensitive mammalian target cell system. It nonetheless proved to have potent adjuvant activity on mucosal and systemic antibody as well as cellular immune responses to mucosally co-administered antigens including oral cholera and intranasal influenza vaccines. We conclude that mmCT is an attractive novel non-toxic mucosal adjuvant for enhancing immune responses to co-administered mucosal vaccines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Antibody and Cytokine Responses of Koalas (Phascolarctos cinereus Vaccinated with Recombinant Chlamydial Major Outer Membrane Protein (MOMP with Two Different Adjuvants.

    Directory of Open Access Journals (Sweden)

    Shahneaz Ali Khan

    Full Text Available Developing a vaccine against Chlamydia is key to combating widespread mortalities and morbidities associated with this infection in koalas (Phascolarctos cinereus. In previous studies, we have shown that two or three doses of a Recombinant Major Outer Membrane Protein (rMOMP antigen-based vaccine, combined with immune stimulating complex (ISC adjuvant, results in strong cellular and humoral immune responses in koalas. We have also separately evaluated a single dose vaccine, utilising a tri-adjuvant formula that comprises polyphosphazine based poly I: C and host defense peptides, with the same antigen. This formulation also produced strong cellular and humoral immune responses in captive koalas. In this current study, we directly compared the host immune responses of two sub-groups of wild Chlamydia negative koalas in one population vaccinated with the rMOMP protein antigen and adjuvanted with either the ISC or tri-adjuvant formula. Overall, both adjuvants produced strong Chlamydia-specific cellular (IFN-γ and IL-17A responses in circulating PBMCs as well as MOMP-specific and functional, in vitro neutralising antibodies. While the immune responses were similar, there were adjuvant-specific immune differences between the two adjuvants, particularly in relation to the specificity of the MOMP epitope antibody responses.

  3. Antibody and Cytokine Responses of Koalas (Phascolarctos cinereus) Vaccinated with Recombinant Chlamydial Major Outer Membrane Protein (MOMP) with Two Different Adjuvants.

    Science.gov (United States)

    Khan, Shahneaz Ali; Desclozeaux, Marion; Waugh, Courtney; Hanger, Jon; Loader, Jo; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

    2016-01-01

    Developing a vaccine against Chlamydia is key to combating widespread mortalities and morbidities associated with this infection in koalas (Phascolarctos cinereus). In previous studies, we have shown that two or three doses of a Recombinant Major Outer Membrane Protein (rMOMP) antigen-based vaccine, combined with immune stimulating complex (ISC) adjuvant, results in strong cellular and humoral immune responses in koalas. We have also separately evaluated a single dose vaccine, utilising a tri-adjuvant formula that comprises polyphosphazine based poly I: C and host defense peptides, with the same antigen. This formulation also produced strong cellular and humoral immune responses in captive koalas. In this current study, we directly compared the host immune responses of two sub-groups of wild Chlamydia negative koalas in one population vaccinated with the rMOMP protein antigen and adjuvanted with either the ISC or tri-adjuvant formula. Overall, both adjuvants produced strong Chlamydia-specific cellular (IFN-γ and IL-17A) responses in circulating PBMCs as well as MOMP-specific and functional, in vitro neutralising antibodies. While the immune responses were similar, there were adjuvant-specific immune differences between the two adjuvants, particularly in relation to the specificity of the MOMP epitope antibody responses.

  4. Modern Vaccines/Adjuvants Formulation Session 6: Vaccine &Adjuvant Formulation & Production 15-17 May 2013, Lausanne, Switzerland.

    Science.gov (United States)

    Fox, Christopher B

    2013-09-01

    The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characterization of adjuvant-antigen interactions, the rational formulation design of a CD8+ T cell-inducing adjuvant based on immunological principles, and the development and production of a rabies vaccine by a developing country manufacturer. Throughout the session, the practical importance of sound formulation and manufacturing design accompanied by analytical characterization was highlighted.

  5. Comparison and Prognostic Analysis of Adjuvant Radiotherapy versus Salvage Radiotherapy for Treatment of Radically Resected Locally Advanced Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Xin Xu

    2016-01-01

    Full Text Available Objective. To compare adjuvant radiotherapy and salvage radiotherapy after radical resection for treatment of esophageal squamous cell carcinoma (ESCC. Methods. Data from 155 patients with locally advanced ESCC who underwent radical resection and received postoperative radiotherapy from 2005 to 2011 were reviewed. Seventy-nine patients received adjuvant radiotherapy and 76 received salvage radiotherapy after locoregional recurrence. Results. The median disease-free survival (DFS and overall survival (OS were significantly higher in the adjuvant radiotherapy group than the salvage radiotherapy group (DFS 25.73 months versus 10.73 months, P 65 years or with PS ≥ 2. Conclusion. Compared to salvage radiotherapy, postoperative adjuvant radiotherapy can prolong DFS and OS for patients with radically resected local advanced ESCC but cannot improve survival for patients aged > 65 years or with PS ≥ 2.

  6. Quantitative detection of HER2 protein concentration in breast cancer tissue does not increase the number of patients eligible for adjuvant HER2-targeted therapy

    DEFF Research Database (Denmark)

    Bechmann, Troels; Olsen, Dorte Aalund; Jakobsen, Erik Hugger;

    2013-01-01

    Human epidermal growth factor receptor-2 (HER2) is overexpressed in 15-20% of breast cancer patients and is associated with an aggressive tumor and a poor prognosis. Currently, patients are selected for adjuvant HER2-targeted therapy based on HER2 status by immunohistochemistry (IHC...... by Centaur, but not treated with adjuvant HER2-targeted therapy, compared to patients defined as HER2-positive by IHC/FISH and therefore treated with adjuvant HER2-targeted therapy. Tumor tissue was obtained at primary surgery from 415 breast cancer patients between 2004 and 2010. HER2 status was determined...... by quantitative immunoassay of fresh-frozen tissue and by IHC/FISH of corresponding paraffin-embedded tissue. We compared the clinical outcome in four groups of patients defined by tissue HER2 status and adjuvant HER2-targeted therapy. The final analysis included 379 patients after a median follow-up of 3.9 years...

  7. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

    Institute of Scientific and Technical Information of China (English)

    Hyung-Sik Lee; Min-Chan Kim; Youngmin Choi; Won-Joo Hur; Hyo-Jin Kim; Hyuk-Chan Kwon; Sung-Hyun Kim; Jae-Seok Kim; Jong-Hoon Lee; Ghap-Joong Jung

    2006-01-01

    AIM: To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection.METHODS: Thirty-one patients who had underwent a potentially curative resection for Stage Ⅲ and Ⅳ (MO) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m2 on d 1 to 5 and cisplatin 60 mg/m2 on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m2 daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo.RESULTS: The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy.Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed.CONCLUSION: These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival.

  8. Ranitidine as adjuvant treatment in colorectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F;

    2002-01-01

    by oral ranitidine 150 mg or placebo twice daily for 5 years. Adjuvant cytotoxic or radiation therapy was not given. An observer-blinded interim analysis performed after 40 months showed that there was no effect of ranitidine on overall survival, and the study was discontinued in accordance......BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS...... curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications....

  9. An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT™ is functionally superior to Freund's adjuvant.

    Science.gov (United States)

    Stevens, Natalie E; Fraser, Cara K; Alsharifi, Mohammed; Brown, Michael P; Diener, Kerrilyn R; Hayball, John D

    2013-01-01

    Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund's adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund's adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.

  10. Which is better for gastric cancer patients, perioperative or adjuvant chemotherapy: a meta-analysis

    OpenAIRE

    2016-01-01

    Background The preferred chemotherapy method for gastric cancer continues to be matter of debate. We performed a meta-analysis to comparing prognosis and safety between perioperative chemotherapy and adjuvant chemotherapy to identify the better chemotherapy option for gastric cancer. Methods We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until February 2016. The main endpoints were prognostic value (hazard ratio [HR] for overall survival [OS] and 1-,...

  11. Development and controversies of adjuvant therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C. H. Lai

    2008-01-01

    BACKGROUND:Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES:A Medline database search was performed to identify relevant articles using the keywords"pancreatic neoplasm", and"adjuvant therapy". Additional papers were identiifed by a manual search of the references from the key articles. RESULTS:Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identiifed. The results for adjuvant regimens based on systemic 5-lfuorouracil with or without external radiotherapy were conlficting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS:Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.

  12. Progress in adjuvant chemotherapy for breast cancer: an overview.

    Science.gov (United States)

    Anampa, Jesus; Makower, Della; Sparano, Joseph A

    2015-01-01

    Breast cancer is the most common cause of cancer and cancer death worldwide. Although most patients present with localized breast cancer and may be rendered disease-free with local therapy, distant recurrence is common and is the primary cause of death from the disease. Adjuvant systemic therapies are effective in reducing the risk of distant and local recurrence, including endocrine therapy, anti-HER2 therapy, and chemotherapy, even in patients at low risk of recurrence. The widespread use of adjuvant systemic therapy has contributed to reduced breast cancer mortality rates. Adjuvant cytotoxic chemotherapy regimens have evolved from single alkylating agents to polychemotherapy regimens incorporating anthracyclines and/or taxanes. This review summarizes key milestones in the evolution of adjuvant systemic therapy in general, and adjuvant chemotherapy in particular. Although adjuvant treatments are routinely guided by predictive factors for endocrine therapy (hormone receptor expression) and anti-HER2 therapy (HER2 overexpression), predicting benefit from chemotherapy has been more challenging. Randomized studies are now in progress utilizing multiparameter gene expression assays that may more accurately select patients most likely to benefit from adjuvant chemotherapy.

  13. Adjuvants for veterinary vaccines--types and modes of action.

    Science.gov (United States)

    Gerdts, Volker

    2015-01-01

    Adjuvants are used to improve the immune response to vaccines. Formulation with adjuvants can result in an earlier onset of immunity, an overall stronger immune response, a specific type of immunity, or a longer duration of immunity to the vaccine. Adjuvants were discovered empirically, and for decades, have been used in both humans and animals without understanding the mechanisms of action. With an improved understanding of the immune system, and in particular the interplay between innate and adaptive immunity, we are now getting better insight into the function of adjuvants. As a result, new adjuvants are being developed that are safe and highly effective for common use in humans and animals, as well as for use in high risk populations such as immunocompromised animals, neonates or very old animals. Furthermore, adjuvants can help to reduce the amount of antigen needed in the vaccine, increase the stability of the vaccine and enable alternatiye administration routes such as needle-free delivery of the vaccine. Here, I will provide an over view of the existing adjuvant technologies for veterinary vaccines and provide an outlook into some of the new technologies in preclinical and clinical development.

  14. Use of adjuvant containing mycobacterial cell-wall skeleton, monophosphoryl lipid A, and squalane in malaria circumsporozoite protein vaccine.

    Science.gov (United States)

    Rickman, L S; Gordon, D M; Wistar, R; Krzych, U; Gross, M; Hollingdale, M R; Egan, J E; Chulay, J D; Hoffman, S L

    1991-04-27

    Human immune responses to modern synthetic and recombinant peptide vaccines administered with the standard adjuvant, aluminum hydroxide, tend to be poor, hence the search for better adjuvants. Antibody responses to a Plasmodium falciparum circumsporozoite (CS) protein vaccine, R32NS1(81), administered with an adjuvant containing cell-wall skeleton of mycobacteria and monophosphoryl lipid A in squalane (MPL/CWS) have been compared to responses to the same immunogen administered with aluminum hydroxide. 2 weeks after the third dose the following indices were greater in the 5 patients who received MPL/CWS than in controls (p less than 0.05): the geometric mean concentration (2.0 vs 25.4 microgram/ml) and avidity index of antibodies to the P falciparum CS protein by ELISA, the geometric mean titre to P falciparum sporozoites by IFAT (1/115 vs 1/1600), and the geometric mean inhibition of sporozoite invasion of hepatoma cells in vitro (37.6 vs 90.3%). For R32NS1(81) MPL/CWS is superior to aluminum hydroxide as an adjuvant, and the data support the evaluation of this complex as an adjuvant for other vaccines.

  15. Endocine™, N3OA and N3OASq; three mucosal adjuvants that enhance the immune response to nasal influenza vaccination.

    Directory of Open Access Journals (Sweden)

    Tina Falkeborn

    Full Text Available Annual outbreaks of seasonal influenza are controlled or prevented through vaccination in many countries. The seasonal vaccines used are either inactivated, currently administered parenterally, or live-attenuated given intranasally. In this study three mucosal adjuvants were examined for the influence on the humoral (mucosal and systemic and cellular influenza A-specific immune responses induced by a nasally administered vaccine. We investigated in detail how the anionic Endocine™ and the cationic adjuvants N3OA and N3OASq mixed with a split inactivated influenza vaccine induced influenza A-specific immune responses as compared to the vaccine alone after intranasal immunization. The study showed that nasal administration of a split virus vaccine together with Endocine™ or N3OA induced significantly higher humoral and cell-mediated immune responses than the non-adjuvanted vaccine. N3OASq only significantly increased the cell-mediated immune response. Furthermore, nasal administration of the influenza vaccine in combination with any of the adjuvants; Endocine™, N3OA or N3OASq, significantly enhanced the mucosal immunity against influenza HA protein. Thus the addition of these mucosal adjuvants leads to enhanced immunity in the most relevant tissues, the upper respiratory tract and the systemic circulation. Nasal influenza vaccination with an inactivated split vaccine can therefore provide an important mucosal immune response, which is often low or absent after traditional parenteral vaccination.

  16. Adjuvants for vaccines to drugs of abuse and addiction.

    Science.gov (United States)

    Alving, Carl R; Matyas, Gary R; Torres, Oscar; Jalah, Rashmi; Beck, Zoltan

    2014-09-22

    Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, because induction of high and prolonged levels of antibodies is required for an effective vaccine, and because injection of T-independent haptenic drugs of abuse does not induce memory recall responses, the role of adjuvants during immunization plays a critical role. As reviewed herein, preclinical studies often use strong adjuvants such as complete and incomplete Freund's adjuvant and others that cannot be, or in the case of many newer adjuvants, have never been, employed in humans. Balanced against this, the only adjuvant that has been included in candidate vaccines in human clinical trials to nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have been widely utilized worldwide in numerous licensed vaccines, the experience with human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse has suggested that the immune responses are too weak to allow development of a successful vaccine. What is needed is an adjuvant or combination of adjuvants that are safe, potent, widely available, easily manufactured, and cost-effective. Based on our review of the field we recommend the following adjuvant combinations either for research or for product development for human use: aluminum salt with adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)]; L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water emulsion containing MPLA.

  17. Adjuvant Strategies for Resectable Pancreatic Cancer: Have We Made Progress?

    Directory of Open Access Journals (Sweden)

    Suzanne Russo

    2012-03-01

    Full Text Available Substantial controversy remains regarding the optimal adjuvant treatment for patients with resectable pancreatic adenocarcinoma. Despite improvements in radiation techniques, systemic therapies, and incorporation of targeted agents, the 5-year survival rates for early stage patients remains less than 25% and the optimal adjuvant treatment approach remains unclear. Here we summarize the data presented at the 2012 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium regarding controversial issues surrounding the role, timing, and selection of patients for adjuvant chemoradiation strategies following curative resection for pancreatic adenocarcinoma. (Abstracts #301, #333, and #206.

  18. The effect of natural adjuvants (G2, G2F on lung inflammation of sensitized guinea pigs

    Directory of Open Access Journals (Sweden)

    Ali Neamati

    2013-07-01

    Full Text Available Objective: The effects of natural adjuvants were examined on total and differential WBC counts in lung lavage of sensitized guinea pigs. Materials and Methods: In three sensitized groups of guinea pigs including: untreated sensitized animals (S, sensitized animals treated with adjuvant G2 (S+G2 and G2F (S+G2F as well as non-sensitized group (C (n=6 for each group, total and differential WBC counts of lung lavage were examined. Sensitization of animals was achieved by injection and inhalation of ovalbumin (OA. Results: The results showed increased total WBC, eosinophil, neutrophil, and basophil counts, and decreased lymphocytes in lung lavage of sensitized animals compared with the control group (pConclusion: These results indicate important preventive effects of two natural adjuvants, especially G2, on lung inflammation of sensitized guinea pigs.  

  19. Two cycles of adjuvant carboplatin in stage I seminoma: 8-year experience by the Hellenic Cooperative Oncology Group (HECOG).

    Science.gov (United States)

    Koutsoukos, Konstantinos; Tzannis, Kimon; Christodoulou, Christos; Karavasilis, Vasilios; Bakoyiannis, Charalambos; Makatsoris, Thomas; Papandreou, C N; Pectasides, Dimitrios; Dimopoulos, Meletios A; Bamias, Aristotelis

    2016-06-01

    Following the establishment of adjuvant carboplatin in stage I testicular seminoma as a standard, we adopted this treatment for all stage I seminoma patients. We report our 8-year experience and compare these results with our previous adjuvant etoposide/cisplatin (EP) strategy. Patients with stage I seminoma, treated with adjuvant carboplatin and with a minimum follow-up of 1 year, were included. Two cycles of carboplatin [area under the curve (AUC) 6] were administered. A total of 138 patients with median age of 34 years, treated from September 2003 to December 2011, were selected. There were 5 relapses [5-year relapse-free rate (RFR) 96.8 % (95 % confidence interval 91.6-98.8)]: 3 relapses at retroperitoneal lymph nodes, 1 relapse at the adrenal gland, and 1 isolated brain metastasis. Four patients with relapse were cured with salvage chemotherapy. All patients with relapse had tumor diameter ≥4 cm and/or age ≤34 years. Patients with at least 1 of the above risk factors (n = 111) had a significantly higher relapse rate compared with a similar population (n = 64) treated with 2 cycles of adjuvant EP: 5-year RFR was 95 % (SE 2 %) versus 100 % (SE 0 %), (p = 0.067). Age and tumor diameter were associated with relapse in stage I seminoma treated with adjuvant carboplatin. Although adjuvant carboplatin in patients with age ≤34 and/or tumor diameter ≥4 cm is associated with higher relapse rates than EP, the prognosis of these patients is excellent, and therefore, the use of less toxic treatment is justified.

  20. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    DEFF Research Database (Denmark)

    Schmidt, Signe Tandrup; Foged, Camilla; Korsholm, Karen Smith;

    2016-01-01

    for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce......The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens...... been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI). Adjuvants constitute a heterogeneous group of compounds, which can broadly...

  1. Fungicides, seed dresser adjuvants and storage time in the control of Drechslera teres in barley seeds

    Directory of Open Access Journals (Sweden)

    Erlei Melo Reis

    2012-09-01

    Full Text Available In experiments conducted in laboratory, the effect of fungicides, seed dresser adjuvants and storage time in the control of Drechslera teres in seeds of barley cultivar BRS Elis, with 58% incidence, was quantified. Fungicides indicated by barley research (carboxin + thiram, difenoconazole and triadimenol compared with the mixture carbendazim + iprodione were tested. As seed dresser adjuvants, water (500m mL/100 Kg and a polymer (150 mL/100 Kg were used. Treated seeds were stored in paper bags and kept in the refrigerator at 5ºC. At 30-day intervals during six months, seeds were plated on semi-selective Reis's medium (1983. The best control was obtained by the mixtures carboxin + thiram and carbendazim + iprodione and the polymer as seed dresser. The control efficiency was improved by the storage time without negatively affecting seed germination. Due to the transmission efficiency, the fungus eradication in seeds should be pursued.

  2. A comparison of weekly versus 3-weekly cisplatin during adjuvant radiotherapy for high-risk head and neck cancer

    NARCIS (Netherlands)

    Oosting, Sjoukje F.; Chen, Tom W. W.; Huang, Shao H.; Wang, Lisa; Waldron, John; Gilbert, Ralph; Goldstein, David; Halmos, Gyorgy B.; Witjes, Max J. H.; Gietema, Jourik A.; O'Sullivan, Brian; Langendijk, Johannes A.; Siu, Lillian L.; Hansen, Aaron R.

    2016-01-01

    Objectives: To compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus weekly cisplatin during adjuvant radiotherapy for high-risk head and neck squamous cell carcinoma (HNSCC). Materials and methods: Consecutive HNSCC patients with involved resection margins and

  3. CAF01 adjuvant increases the protection conferred by a commercially available influenza split vaccine in a ferret model

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Jensen, Trine Hammer; Nielsen, Lars Peter;

    , we compared the immune response in ferrets vaccinated with a commercial influenza split vaccine with the same vaccine mixed with the CAF01 adjuvant and furthermore used two recently circulating H1N1 viruses for the challenge of the animals. We investigated antibody levels in serum and nasal washes...

  4. The Vaccine Formulation Laboratory: a platform for access to adjuvants.

    Science.gov (United States)

    Collin, Nicolas; Dubois, Patrice M

    2011-07-01

    Adjuvants are increasingly used by the vaccine research and development community, particularly for their ability to enhance immune responses and for their dose-sparing properties. However, they are not readily available to the majority of public sector vaccine research groups, and even those with access to suitable adjuvants may still fail in the development of their vaccines because of lack of knowledge on how to correctly formulate the adjuvants. This shortcoming led the World Health Organization to advocate for the establishment of the Vaccine Formulation Laboratory at the University of Lausanne, Switzerland. The primary mission of the laboratory is to transfer adjuvants and formulation technology free of intellectual property rights to academic institutions, small biotechnology companies and developing countries vaccine manufacturers. In this context, the transfer of an oil-in-water emulsion to Bio Farma, an Indonesian vaccine manufacturer, was initiated to increase domestic pandemic influenza vaccine production capacity as part of the national pandemic influenza preparedness plan.

  5. Editorial: Short-course adjuvant trastuzumab will increase cure rates ...

    African Journals Online (AJOL)

    Editorial: Short-course adjuvant trastuzumab will increase cure rates in patients with human epidermal growth factor receptor 2-positive breast cancer. ... Journal Home > Vol 107, No 8 (2017) >. Log in or Register to get ... from 32 Countries:.

  6. Endometrial adenocarcinoma, adjuvant radiotherapy tailored to prognostic factors.

    Science.gov (United States)

    Meerwaldt, J H; Hoekstra, C J; van Putten, W L; Tjokrowardojo, A J; Koper, P C

    1990-02-01

    The optimal adjuvant radiotherapy for surgically treated endometrial cancer has not yet been defined. We report on 389 patients treated between 1970 and 1985 with adjuvant radiotherapy. The treatment was tailored to the known prognostic factors: myometrial invasion and grade of differentiation of the tumor. Ten-year overall survival was 67%, 10-year relapse-free survival 77%; 23% relapse, of which 21% distant and 6% locoregional relapse. In a multivariate analysis, stage (pT), grade, and myometrial invasion were prognostic factors. The number of locoregional failures was very small (n = 23). This small number, the fact that radiation treatment was tailored to prognostic factors, and the absence of a nontreated control group precluded an analysis of the effect of the adjuvant irradiation. Large randomized studies with a control (no treatment) arm should be performed to determine the value of adjuvant radiotherapy.

  7. Triple negative breast cancer: adjuvant chemotherapy effect on survival

    National Research Council Canada - National Science Library

    Steponaviciene, L; Lachej-Mikeroviene, N; Smailyte, G; Aleknavicius, E; Meskauskas, R; Didziapetriene, J

    2011-01-01

    Purpose: The purpose of this study was to evaluate the overall survival of patients with triple negative breast cancer and the impact of different adjuvant chemotherapy regimens on survival.Material/Methods...

  8. Mx bio adjuvant for enhancing immune responses against influenza virus

    Directory of Open Access Journals (Sweden)

    Sina Soleimani

    2015-06-01

    Conclusion: These data revealed that Mx1 as biological adjuvant was able to increase antibody titer and induction memory immune responses against influenza immunization without causing any side effects.

  9. Adjuvant Radiation Therapy and Survival for Pure Tubular Breast Carcinoma-Experience From the SEER Database

    Energy Technology Data Exchange (ETDEWEB)

    Li Baoqing, E-mail: bal9018@med.cornell.edu [Department of Radiation Oncology, Weill Cornell Medical College, New York, New York (United States); Chen, Margaret [Department of Surgery, Weill Cornell Medical College, New York, New York (United States); Nori, Dattatreyudu; Chao, K.S. Clifford [Department of Radiation Oncology, Weill Cornell Medical College, New York, New York (United States); Chen, Allen M. [Department of Radiation Oncology, University of California Davis Cancer Center, Sacramento, California (United States); Chen, Steven L. [Department of Surgery, University of California Davis Cancer Center, Sacramento, California (United States)

    2012-09-01

    Purpose: Pure tubular carcinoma of the breast (PTCB) represents a distinct subtype of invasive ductal carcinoma (IDC) that is generally thought to be associated with better prognosis than even low-grade IDC. There has been controversy as to the role of adjuvant radiation therapy (RT) in this population. We hypothesized that adjuvant RT would demonstrate a survival improvement. Methods and Materials: We queried the Surveillance, Epidemiology and End Results database for the years 1992-2007 to identify patients with pure tubular carcinomas of the breast. Patient demographics, tumor characteristics, and surgical and RT treatments were collected. Survival analysis was performed using the Kaplan-Meier method for univariate comparisons and Cox proportional hazards modeling for multivariate comparisons, stratifying on the basis of age with a cutoff age of 65. Results: A total of 6465 patients were identified: 3624 (56.1%) patients underwent lumpectomy with RT (LUMP+RT), 1525 (23.6%) patients underwent lumpectomy alone (LUMP), 1266 (19.6%) patients received mastectomy alone (MAST), and 50 (0.8%) patients underwent mastectomy with RT (MAST+RT). When we compared the LUMP+RT and LUMP groups directly, those receiving adjuvant RT tended to be younger and were less likely to be hormone receptor-positive. Overall survival was 95% for LUMP+RT and 90% for LUMP patients at 5 years. For those 65 or younger, the absolute overall survival benefit of LUMP+RT over LUMP was 1% at 5 years and 3% at 10 years. On stratified multivariate analysis, adjuvant RT remained a significant predictor in both age groups (P=.003 in age {<=}65 and P=.04 in age >65 patients). Other significant unfavorable factors were older age and higher T stage (age >65 only). Conclusions: Since sufficiently powered large scale clinical trials are unlikely, we would recommend that adjuvant radiation be considered in PTCB patients age 65 or younger, although consideration of the small absolute survival benefit is

  10. Adjuvant endocrine therapy alone in patients with node-positive, luminal A type breast cancer.

    Science.gov (United States)

    Park, Sungmin; Lee, Se Kyung; Paik, Hyun-June; Ryu, Jai Min; Kim, Isaac; Bae, Soo Youn; Yu, Jonghan; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin

    2017-06-01

    Luminal A breast cancer has a much better prognosis than other subtypes, with a low risk of local or regional recurrence. However, there is controversy around under- versus overtreatment with regard to adjuvant treatment of node-positive, luminal A breast cancer. The purpose of this study was to identify whether adjuvant systemic chemotherapy has any benefit in node-positive, luminal A breast cancer and to evaluate feasibility of endocrine therapy without chemotherapy in this group.This was a retrospective study of 11,025 patients who were surgically treated for invasive breast cancer at Samsung Medical Center between January 2004 and December 2013. Luminal A subtype was defined as ER+, HER2-, and Ki-67 < 14%. We compared AC based (AC: doxorubicin or epirubicin, plus cyclophosphamide) adjuvant chemotherapy versus endocrine therapy without chemotherapy in patients with node-positive, luminal A breast cancer.We performed 1: n matching, with a maximum n of 8 on endocrine therapy group (n = 50) to chemotherapy group (n = 642). The median age of the patients in each group at the time of surgery was 58.3 ± 9.5 years in the chemotherapy group and 58.7 ± 11.7 in the endocrine therapy only group. The median follow-up time was 51.9 months (range, 1-125 months). In multivariable analysis, omission of adjuvant chemotherapy in luminal A cancer had no influence on OS and DFS. Axillary lymph node metastasis and progesterone receptor (PR) status were significantly different between the endocrine therapy alone group and the chemotherapy group in terms of OS. Nuclear grade, PR status, and adjuvant radiotherapy were significantly different between the endocrine therapy alone group and the chemotherapy group with regard to DFS. In survival analysis, there were no differences in OS (P = .137) and DFS (P = .225) between the 2 groups.Adjuvant chemotherapy could provide little benefit to postmenopausal patients with luminal A, node-positive breast cancer, and

  11. Teaching adjuvant endocrine breast cancer treatment to medical students.

    Science.gov (United States)

    de Visser, M; Fluit, C; Timmer-Bonte, J; Ottevanger, P; Verhagen, C; Klaassen, T; van Laarhoven, H W M

    2013-05-01

    In undergraduate medical education, students are supposed to acquire knowledge and understanding about the basic principles of adjuvant breast cancer treatment. The best education method in this context is unknown. In this randomised study we assessed the effect of designing a patient education poster on knowledge, perceived participation and students' satisfaction compared with case-oriented education concerning endocrine therapy for breast cancer patients. This study was conducted in the Bachelor Oncology Course for undergraduate students in Medical Science of the Radboud University Nijmegen Medical Centre. In the experimental group, students designed and created a patient education poster in small groups. In the control group, students answered case-based questions in small groups. Knowledge was tested at different moments using multiple-choice questions. To assess perceived participation and satisfaction, students filled out questionnaires. 329 students participated in the study. No difference in knowledge was observed between the experimental and control group. However, students in the control group reported a higher perceived participation and satisfaction compared with the students in the experimental group (pstudents' perceived participation and satisfaction. Working on case-based questions may be appreciated by medical students as most relevant for their future profession. We advocate more attention to the importance of patient education in the medical curriculum, to help students realise the relevance of this aspect of medical profession.

  12. Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle

    2013-01-01

    The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

  13. Learning impairment in honey bees caused by agricultural spray adjuvants.

    Directory of Open Access Journals (Sweden)

    Timothy J Ciarlo

    Full Text Available BACKGROUND: Spray adjuvants are often applied to crops in conjunction with agricultural pesticides in order to boost the efficacy of the active ingredient(s. The adjuvants themselves are largely assumed to be biologically inert and are therefore subject to minimal scrutiny and toxicological testing by regulatory agencies. Honey bees are exposed to a wide array of pesticides as they conduct normal foraging operations, meaning that they are likely exposed to spray adjuvants as well. It was previously unknown whether these agrochemicals have any deleterious effects on honey bee behavior. METHODOLOGY/PRINCIPAL FINDINGS: An improved, automated version of the proboscis extension reflex (PER assay with a high degree of trial-to-trial reproducibility was used to measure the olfactory learning ability of honey bees treated orally with sublethal doses of the most widely used spray adjuvants on almonds in the Central Valley of California. Three different adjuvant classes (nonionic surfactants, crop oil concentrates, and organosilicone surfactants were investigated in this study. Learning was impaired after ingestion of 20 µg organosilicone surfactant, indicating harmful effects on honey bees caused by agrochemicals previously believed to be innocuous. Organosilicones were more active than the nonionic adjuvants, while the crop oil concentrates were inactive. Ingestion was required for the tested adjuvant to have an effect on learning, as exposure via antennal contact only induced no level of impairment. CONCLUSIONS/SIGNIFICANCE: A decrease in percent conditioned response after ingestion of organosilicone surfactants has been demonstrated here for the first time. Olfactory learning is important for foraging honey bees because it allows them to exploit the most productive floral resources in an area at any given time. Impairment of this learning ability may have serious implications for foraging efficiency at the colony level, as well as potentially many

  14. Effect of Freund's adjuvant on standard dark and pastel mink.

    Science.gov (United States)

    Tabel, H; Ingram, D G

    1971-04-01

    Following a long series of injections of homologous immunoglobulin in complete and incomplete Freund's adjuvant into mink, a moderate elevation in the level of gammaglobulin in the serum was observed in a few animals. Relatively mild pathological changes also were seen in liver, spleen, lymph nodes, lungs and kidney. It is concluded that the injection of Freund's adjuvant, under the experimental conditions described, produced lesions which were readily distinguishable from the lesions characteristic of aleutian disease of mink.

  15. Use of non-opioid analgesics as adjuvants to opioid analgesia for cancer pain management in an inpatient palliative unit: does this improve pain control and reduce opioid requirements?

    Science.gov (United States)

    Shinde, Shivani; Gordon, Pamela; Sharma, Prashant; Gross, James; Davis, Mellar P

    2015-03-01

    Cancer pain is complex, and despite the introduction of the WHO cancer pain ladder, few studies have looked at the prevalence of adjuvant medication use in an inpatient palliative medicine unit. In this study, we evaluate the use of adjuvant pain medications in patients admitted to an inpatient palliative care unit and whether their use affects pain scores or opiate dosing. In this retrospective observational study, patients admitted to the inpatient palliative care unit over a 3-month period with a diagnosis of cancer on opioid therapy were selected. Data pertaining to demographics, diagnosis, oral morphine dose equivalent of the opioid at the time of discharge, adjuvant analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and pain scores as reported by nurses and physicians were collected. Seventy-seven patients were eligible over a 3-month period, out of which 65 (84 %) were taking an adjuvant medication. The most commonly prescribed adjuvant was gabapentin (70 %). Fifty-seven percent were taking more than one adjuvant. There were more women in the group receiving adjuvants (57 vs. 17%, p = 0.010). Those without adjuvants compared with those on adjuvants did not have worse pain scores on discharge as reported by physicians (0.8 ± 0.8 vs. 1.0 ± 0.7, p = 0.58) or nurses (2.0 ± 2.7 vs. 2.1 ± 2.6, p = 0.86). There was no difference in morphine equivalent doses of the opioid in both groups (median (min, max); 112 (58, 504) vs. 200 (30, 5,040)) at the time of discharge; 75-80 % of patients had improvement in pain scores as measured by a two-point reduction in numerical rating scale (NRS). This study shows that adjuvant medications are commonly used for treating pain in patients with cancer. More than half of study population were on two adjuvants or an adjuvant plus NSAID along with an opioid. We did not demonstrate any benefit in terms of improved pain scores or opioid doses with adjuvants, but this could reflect confounding variables and physician choice

  16. Autoimmune/Inflammatory Syndrome Induced by Adjuvants and Thyroid Autoimmunity

    Science.gov (United States)

    Watad, Abdulla; David, Paula; Brown, Stav; Shoenfeld, Yehuda

    2017-01-01

    The autoimmune/inflammatory syndrome induced by adjuvants (ASIA), presented by Shoenfeld and Agmon-Levin in 2011, is an entity that incorporates diverse autoimmune conditions induced by the exposure to various adjuvants. Adjuvants are agents that entail the capability to induce immune reactions. Adjuvants are found in many vaccines and used mainly to increase the response to vaccination in the general population. Silicone has also been reported to be able to induce diverse immune reactions. Clinical cases and series of heterogeneous autoimmune conditions including systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis have been reported to be induced by several adjuvants. However, only a small number of cases of autoimmune thyroid disorder have been included under the umbrella of ASIA syndrome. Indeed, clinical cases of Hashimoto’s thyroiditis and/or subacute thyroiditis were observed after the exposure to vaccines as well as silicone implantation. In our review, we aimed to summarize the current knowledge on ASIA syndrome presented as endocrinopathies, focusing on autoimmune thyroid disorders associated with the various adjuvants. PMID:28167927

  17. Communicating the role and value of vaccine adjuvants.

    Science.gov (United States)

    Gellin, Bruce G; Salisbury, David M

    2015-06-08

    Despite the inclusion of adjuvants in many routinely used vaccines to improve the immune response, their presence and role are neither clear in product details such as the packaging or in the Summaries of Product Characteristics, nor understood by health professionals or the public. For many vaccines the adjuvant may simply be described as 'Adsorbed' without clarification that the adsorbing onto a material such as aluminium hydroxide adjuvants the antigens. As many future vaccines are likely to be adjuvanted, the presence of adjuvants, either those used in existing vaccines or novel formulations, may raise public and professional concerns unless communication materials are prepared in advance to allay anxieties such as those that have arisen over some present vaccine ingredients such as thiomersal. This raises a dilemma about how active such communications should be: over-promotion of the presence of a new adjuvant may cause unneeded anxieties; under-promotion may raise concerns over concealment of information. Research is needed and appropriate communication materials should be prepared. Copyright © 2015. Published by Elsevier Ltd.

  18. Squalene and squalane emulsions as adjuvants.

    Science.gov (United States)

    Allison, A C

    1999-09-01

    Microfluidized squalene or squalane emulsions are efficient adjuvants, eliciting both humoral and cellular immune responses. Microfluidization stabilizes the emulsions and allows sterilization by terminal filtration. The emulsions are stable for years at ambient temperature and can be frozen. Antigens are added after emulsification so that conformational epitopes are not lost by denaturation and to facilitate manufacture. A Pluronic block copolymer can be added to the squalane or squalene emulsion. Soluble antigens administered in such emulsions generate cytotoxic T lymphocytes able to lyse target cells expressing the antigen in a genetically restricted fashion. Optionally a relatively nontoxic analog of muramyl dipeptide (MDP) or another immunomodulator can be added; however, the dose of MDP must be restricted to avoid systemic side effects in humans. Squalene or squalane emulsions without copolymers or MDP have very little toxicity and elicit potent antibody responses to several antigens in nonhuman primates. They could be used to improve a wide range of vaccines. Squalene or squalane emulsions have been administered in human cancer vaccines, with mild side effects and evidence of efficacy, in terms of both immune responses and antitumor activity.

  19. Predictive value of Ki67 for adjuvant chemotherapy in node-negative, hormone receptor-positive breast cancer.

    Science.gov (United States)

    Sutepvarnon, Apisada; Warnnissorn, Malee; Srimuninnimit, Vichien

    2013-02-01

    Ki67 labeling index (Ki67 LI) is a measure of tumor proliferation. In breast cancer, evidence supporting its prognostic value is clear and its predictive value for response to treatment finds some benefits. However studies of Ki67 LI as a predictive marker in early breast cancer are still limited worldwide and there is no data in Thailand. To assess the predictive value of Ki67 expression for adjuvant chemotherapy in patients with node-negative, hormone receptor-positive breast cancer The authors retrospectively evaluated 127 diagnosed early breast cancer with node-negative, hormone receptor-positive patients and receiving adjuvant systemic treatment at Siriraj hospital. Disease free survival (DFS) was compared with the log-rank test according to Ki67 LI and adjuvant systemic treatment (chemoendocrine therapy and endocrine therapy alone). At a median follow-up of 3.3 years. The 5-year DFS rate was 79% for patients with low Ki67 expression and 75% for patients with high Ki67 expression. Of the 127 patients, 56 (44.1%) received chemoendocrine therapy and 71 (55.9%) were treated with endocrine therapy alone. There was no different effect of DFS among those receiving adjuvant endocrine therapy alone and those receiving adjuvant chemoendocrine therapy depending on Ki67 expression. Among patients with node-negative, hormone receptor-positive breast cancer, a high Ki67 LI had worse DFS trend than a low Ki67 LI but the Ki67 LI did not predict the efficacy of adjuvant chemotherapy.

  20. Effects of 3% trehalose as an adjuvant treatment after LASIK

    Directory of Open Access Journals (Sweden)

    Mateo Orobia AJ

    2017-02-01

    Full Text Available Antonio J Mateo Orobia,1–3 Paula Casas Pascual,1,4 José Á Cristóbal Bescós,1 Diana Perez García,1,4 Carlos Peiro Embid,1,4 M Ángeles del Buey Sayas,1,4 Valentyna Korobko Kulikova,1 Noelia Lafuente Ojeda5 1Department of Ophthalmology, Hospital Quirón, 2Department of Ophthalmology, Hospital Universitario Miguel Servet, 3Instituto de Investigación Sanitaria de Aragón (IIS, 4Department of Ophthalmology, Hospital Clínico Universitario Lozano-Blesa, 5Department of Anesthesiology, Hospital Universitario Miguel Servet, Zaragoza, Spain Purpose: To evaluate the effect of 3% trehalose as an adjuvant in the standard treatment after laser-assisted in situ keratomileusis.Design: Interventional prospective comparative single-blind study.Setting: Department of Ophthalmology, Hospital Quirón Zaragoza, Spain.Methods: A total of 26 eyes (13 patients were included, of which 12 eyes (group 1 received conventional treatment with lubricant drops of hyaluronic acid (0.15% and 14 eyes (group 2 received, additionally, an ophthalmic solution of 3% trehalose. Pre- and postoperative quality-of-life tests and vital stains, tear breakup time, and osmolarity measurements were made.Results: We obtained statistically significant differences between the groups in the Symptom Assessment in Dry Eye test in all visits with respect to severity, and in the postoperative day 1 visit with respect to frequency, in all cases favoring the trehalose treatment. The values of osmolarity were not significantly different between groups. However, we did find significant differences in the Oxford scale in day 90 for the trehalose treatment (P<0.001, and in the National Eye Institute scale in day 30 (P=0.02.Conclusion: The results of this exploratory study indicate that the adjuvant treatment with 3% trehalose could be superior with respect to the standard treatment, with improvements in the objective and subjective parameters of tear quality. Keywords: dry eye syndrome, trehalose

  1. Evaluation of Montanide™ ISA 71 VG adjuvant during profilin vaccination against experimental coccidiosis.

    Science.gov (United States)

    Jang, Seung I; Kim, Duk Kyung; Lillehoj, Hyun S; Lee, Sung Hyen; Lee, Kyung Woo; Bertrand, François; Dupuis, Laurent; Deville, Sébastien; Ben Arous, Juliette; Lillehoj, Erik P

    2013-01-01

    Chickens were immunized subcutaneously with an Eimeria recombinant profilin protein plus Montanide™ ISA 70 VG (ISA 70) or Montanide™ ISA 71 VG (ISA 71) water-in-oil adjuvants, or with profilin alone, and comparative RNA microarray hybridizations were performed to ascertain global transcriptome changes induced by profilin/ISA 70 vs. profilin alone and by profilin/ISA 71 vs. profilin alone. While immunization with profilin/ISA 70 vs. profilin alone altered the levels of more total transcripts compared with profilin/ISA 71 vs. profilin alone (509 vs. 296), the latter was associated with a greater number of unique biological functions, and a larger number of genes within these functions, compared with the former. Further, canonical pathway analysis identified 10 pathways that were associated with genes encoding the altered transcripts in animals immunized with profilin/ISA 71 vs. profilin alone, compared with only 2 pathways in profilin/ISA 70 vs. profilin alone. Therefore, ISA 71 was selected as a candidate adjuvant in conjunction with profilin vaccination for in vivo disease protection studies. Vaccination with profilin/ISA 71 was associated with greater body weight gain following E. acervulina infection, and decreased parasite fecal shedding after E. maxima infection, compared with profilin alone. Anti-profilin antibody levels were higher in sera of E. maxima- and E. tenella-infected chickens vaccinated with profilin/ISA 71 compared with profilin alone. Finally, the levels of transcripts encoding interferon-γ, interleukin (IL)-2, IL-10, and IL-17A were increased in intestinal lymphocytes from E. acervulina-, E. maxima-, and/or E. tenella-infected chickens vaccinated with profilin/ISA 71 compared with profilin alone. None of these effects were seen in chickens injected with ISA 71 alone indicating that the adjuvant was not conferring non-specific immune stimulation. These results suggest that profilin plus ISA 71 augments protective immunity against selective

  2. Evaluation of Montanide™ ISA 71 VG adjuvant during profilin vaccination against experimental coccidiosis.

    Directory of Open Access Journals (Sweden)

    Seung I Jang

    Full Text Available Chickens were immunized subcutaneously with an Eimeria recombinant profilin protein plus Montanide™ ISA 70 VG (ISA 70 or Montanide™ ISA 71 VG (ISA 71 water-in-oil adjuvants, or with profilin alone, and comparative RNA microarray hybridizations were performed to ascertain global transcriptome changes induced by profilin/ISA 70 vs. profilin alone and by profilin/ISA 71 vs. profilin alone. While immunization with profilin/ISA 70 vs. profilin alone altered the levels of more total transcripts compared with profilin/ISA 71 vs. profilin alone (509 vs. 296, the latter was associated with a greater number of unique biological functions, and a larger number of genes within these functions, compared with the former. Further, canonical pathway analysis identified 10 pathways that were associated with genes encoding the altered transcripts in animals immunized with profilin/ISA 71 vs. profilin alone, compared with only 2 pathways in profilin/ISA 70 vs. profilin alone. Therefore, ISA 71 was selected as a candidate adjuvant in conjunction with profilin vaccination for in vivo disease protection studies. Vaccination with profilin/ISA 71 was associated with greater body weight gain following E. acervulina infection, and decreased parasite fecal shedding after E. maxima infection, compared with profilin alone. Anti-profilin antibody levels were higher in sera of E. maxima- and E. tenella-infected chickens vaccinated with profilin/ISA 71 compared with profilin alone. Finally, the levels of transcripts encoding interferon-γ, interleukin (IL-2, IL-10, and IL-17A were increased in intestinal lymphocytes from E. acervulina-, E. maxima-, and/or E. tenella-infected chickens vaccinated with profilin/ISA 71 compared with profilin alone. None of these effects were seen in chickens injected with ISA 71 alone indicating that the adjuvant was not conferring non-specific immune stimulation. These results suggest that profilin plus ISA 71 augments protective immunity

  3. Self-Adjuvanting Bacterial Vectors Expressing Pre-Erythrocytic Antigens Induce Sterile Protection against Malaria

    Directory of Open Access Journals (Sweden)

    Elke eBergmann-Leitner

    2013-07-01

    Full Text Available Genetically inactivated, Gram-negative bacteria that express malaria vaccine candidates represent a promising novel self-adjuvanting vaccine approach. Antigens expressed on particulate bacterial carriers not only target directly to antigen-presenting cells but also provide a strong danger signal thus circumventing the requirement for potent extraneous adjuvants. E. coli expressing malarial antigens resulted in the induction of either Th1 or Th2 biased responses that were dependent on both antigen and sub-cellular localization. Some of these constructs induced higher quality humoral responses compared to recombinant protein and most importantly they were able to induce sterile protection against sporozoite challenge in a murine model of malaria. In light of these encouraging results, two major Plasmodium falciparum pre-erythrocytic malaria vaccine targets, the Cell-Traversal protein for Ookinetes and Sporozoites (CelTOS fused to the Maltose-binding protein in the periplasmic space and the Circumsporozoite Protein (CSP fused to the Outer membrane protein A in the outer membrane were expressed in a clinically relevant, attenuated Shigella strain (Shigella flexneri 2a. This type of live attenuated vector has previously undergone clinical investigations as a vaccine against shigellosis. Using this novel delivery platform for malaria, we find that vaccination with the whole organism represents an effective vaccination alternative that induces protective efficacy against sporozoite challenge. Shigella GeMI-Vax expressing malaria targets warrant further evaluation to determine their full potential as a dual disease, multivalent, self-adjuvanting vaccine system, against both shigellosis and malaria.

  4. A genetically adjuvanted influenza B virus vector increases immunogenicity and protective efficacy in mice.

    Science.gov (United States)

    Kittel, Christian; Wressnigg, Nina; Shurygina, Anna Polina; Wolschek, Markus; Stukova, Marina; Romanovskaya-Romanko, Ekatherina; Romanova, Julia; Kiselev, Oleg; Muster, Thomas; Egorov, Andrej

    2015-10-01

    The existence of multiple antigenically distinct types and subtypes of influenza viruses allows the construction of a multivalent vector system for the mucosal delivery of foreign sequences. Influenza A viruses have been exploited successfully for the expression of extraneous antigens as well as immunostimulatory molecules. In this study, we describe the development of an influenza B virus vector whose functional part of the interferon antagonist NS1 was replaced by human interleukin 2 (IL2) as a genetic adjuvant. We demonstrate that IL2 expressed by this viral vector displays immune adjuvant activity in immunized mice. Animals vaccinated with the IL2 viral vector showed an increased hemagglutination inhibition antibody response and higher protective efficacy after challenge with a wild-type influenza B virus when compared to mice vaccinated with a control virus. Our results demonstrate that it is feasible to construct influenza B vaccine strains expressing immune-potentiating foreign sequences from the NS genomic segment. Based on these data, it is now hypothetically possible to create a trivalent (or quadrivalent) live attenuated influenza vaccine in which each component expresses a selected genetic adjuvant with tailored expression levels.

  5. Adjuvant effect enhancement of porcine interleukin-2 packaged into solid lipid nanoparticles.

    Science.gov (United States)

    Chen, Guohua; Zeng, Shuang; Jia, Huaijie; He, Xiaobing; Fang, Yongxiang; Jing, Zhizhong; Cai, Xuepeng

    2014-02-01

    In this paper, we investigated the enhancement of adjuvant effects of porcine IL-2 (pIL-2) by packaging it into a solid lipid nanoparticle (SLN) delivery system. SLN-pIL-2 was prepared using hydrogenated castor oil and Polylactide-co-glycolide by double emulsion solvent evaporation methods (w/o/w). In animal trials, BALB/c mice were immunized with inactivated foot and mouth disease virus (FMDV) antigen combined with the SLN-pIL-2 adjuvant on days 0 and 14. Antibody titer, splenocyte proliferation, and secretion of IFN-γ and IL-4 cytokines were determined. Our results showed that SLN-pIL-2 could significantly enhance FMDV-specific antibody level compared with recombinant pIL-2 alone (pSLN-pIL-2 significantly increased the proliferative responses of antigen-specific spleen cells. Furthermore, SLN-pIL-2 induced the secretion of IFN-γ at a level higher than that induced by recombinant pIL-2 alone. Our results indicate that packaging recombinant pIL-2 in SLNs can be an effective way of boosting the effectiveness of pIL-2 as an adjuvant to enhance immune responses of vaccines.

  6. Comparison of adjuvant formulations for cytotoxic T cell induction using synthetic peptides.

    Science.gov (United States)

    Hioe, C E; Qiu, H; Chend, P D; Bian, Z; Li, M L; Li, J; Singh, M; Kuebler, P; McGee, P; O'Hagan, D; Zamb, T; Koff, W; Allsopp, C; Wang, C Y; Nixon, D F

    1996-04-01

    We have investigated the capacity of synthetic peptides delivered in different adjuvant formulations to induce cytotoxic T lymphocyte (CTL) responses to a class I H-2Kd-restricted Plasmodium berghei circumsporozoite epitope, CS 252-260. Using three immunogen formulations: soybean emulsion; Montanide ISA720; and lipopeptide (P3-CS), we first evaluated the effects of immunization routes on CTL induction. No CTL response was induced in mice immunized s.c. or i.p. with CS peptide formulated in soybean emulsion. In contrast, immunization with lipopeptide P3-CS either s.c. or i.p. effectively primed for CTL. Interestingly, CS peptide emulsified in Montanide ISA720 induced a CTL response only when delivered s.c. and not i.p., indicating the critical influence of immunization routes on CTL induction. We then compared the effectiveness of eight adjuvant formulations to induce CTL response following a single s.c. immunization. Notably, lipopeptide P3-CS and CS peptide admixed with P3 or POE lipid molecules stimulated a vigorous CTL response. However, only mice immunized with P3-CS and CS peptide admixed with P3 molecule generated long-lived CTL which persisted in vivo for 5 months. Thus, based on a simultaneous comparison of the different adjuvant formulations, we demonstrated that the conjugated and unconjugated P3 lipopeptides were the most effective immunogens for eliciting primary and memory CTL in mice.

  7. Preferences for oral versus intravenous adjuvant chemotherapy among early breast cancer patients

    Directory of Open Access Journals (Sweden)

    Ishitobi M

    2013-11-01

    Full Text Available Makoto Ishitobi,1 Kazuyo Shibuya,2 Yoshifumi Komoike,1 Hiroki Koyama,1 Hideo Inaji1 1Department of Breast and Endocrine Surgery, 2Department of Nursing, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan Purpose: The purpose of this study was to evaluate preferences for oral versus intravenous adjuvant chemotherapy among early breast cancer patients (UMIN-CTR number UMIN000004696. Patients and methods: Eighty-two postmenopausal women with estrogen receptor-positive, human epidermal growth-factor receptor 2-negative breast cancer who had completed adjuvant chemotherapy were asked about their preferred route of administration of chemotherapy and the reason. Women also answered questions about their physical and psychological status and quality of life during chemotherapy. Results: Patients who had received oral chemotherapy preferred it more frequently than those who had received intravenous chemotherapy (100% versus 37%, respectively, chi-square =15.5; P<0.001. Patients who preferred the same route of administration of chemotherapy as they had previously received showed a significantly better psychological status during chemotherapy compared with those who preferred a different route. Conclusion: Our study showed that preferences for oral and intravenous chemotherapy strongly depended on the actual prior administration of chemotherapy and patients' own experiences during chemotherapy. Keywords: breast cancer, adjuvant, chemotherapy, patient preference, oral, intravenous

  8. Dendrimer-like alpha-d-glucan nanoparticles activate dendritic cells and are effective vaccine adjuvants.

    Science.gov (United States)

    Lu, Fangjia; Mencia, Alejandra; Bi, Lin; Taylor, Aaron; Yao, Yuan; HogenEsch, Harm

    2015-04-28

    The use of nanoparticles for delivery of vaccine antigens and as vaccine adjuvants is appealing because their size allows efficient uptake by dendritic cells and their biological properties can be tailored to the desired function. Here, we report the effect of chemically modified phytoglycogen, a dendrimer-like α-d-glucan nanoparticle, on dendritic cells in vitro, and the utility of this type of nanoparticle as a vaccine adjuvant in vivo. The modified phytoglycogen nanoparticle, termed Nano-11, has a positive surface charge which enabled electrostatic adsorption of negatively charged protein antigens. The Nano-11-antigen complexes were efficiently phagocytized by dendritic cells. Nano-11 induced increased expression of costimulatory molecules and the secretion of IL-1β and IL-12p40 by dendritic cells. Intramuscular injection of Nano-11-antigen formulations induced a significantly enhanced immune response to two different protein antigens. Examination of the injection site revealed numerous monocytes and relatively few neutrophils at one day after injection. The inflammation had nearly completely disappeared by 2 weeks after injection. These studies indicate that Nano-11 is an effective vaccine delivery vehicle that significantly enhances the immune response. This type of plant based nanoparticle is considered highly cost-effective compared with fully synthetic nanoparticles and appears to have an excellent safety profile making them an attractive adjuvant candidate for prophylactic vaccines.

  9. Adjuvants and immunization strategies to induce influenza virus hemagglutinin stalk antibodies.

    Directory of Open Access Journals (Sweden)

    Peter H Goff

    Full Text Available The global population remains vulnerable in the face of the next pandemic influenza virus outbreak, and reformulated vaccinations are administered annually to manage seasonal epidemics. Therefore, development of a new generation of vaccines is needed to generate broad and persistent immunity to influenza viruses. Here, we describe three adjuvants that enhance the induction of stalk-directed antibodies against heterologous and heterosubtypic influenza viruses when administered with chimeric HA proteins. Addavax, an MF59-like nanoemulsion, poly(I:C, and an RNA hairpin derived from Sendai virus (SeV Cantell were efficacious intramuscularly. The SeV RNA and poly(I:C also proved to be effective respiratory mucosal adjuvants. Although the quantity and quality of antibodies induced by the adjuvants varied, immunized mice demonstrated comparable levels of protection against challenge with influenza A viruses on the basis of HA stalk reactivity. Finally, we present that intranasally, but not intramuscularly, administered chimeric HA proteins induce mucosal IgA antibodies directed at the HA stalk.

  10. Immunogenicity and protective efficacy of a vaxfectin-adjuvanted tetravalent dengue DNA vaccine.

    Science.gov (United States)

    Porter, Kevin R; Ewing, Daniel; Chen, Lan; Wu, Shuenn-Jue; Hayes, Curtis G; Ferrari, Marilyn; Teneza-Mora, Nimfa; Raviprakash, Kanakatte

    2012-01-05

    A prototype dengue-1 DNA vaccine was shown to be safe and immunogenic in a previous Phase 1 clinical trial. Anti-dengue-1 neutralizing antibody responses were detectable only in the group of volunteers receiving the high dose of nonadjuvanted vaccine and the antibody titers were low. Vaxfectin(®), a lipid-based adjuvant, enhances the immunogenicity of DNA vaccines. We conducted a nonhuman primate study to evaluate the effect of Vaxfectin(®) on the immunogenicity of a tetravalent dengue DNA vaccine. Animals were immunized on days 0, 28 and 84, with each immunization consisting of 3mg of Vaxfectin(®)-adjuvanted tetravalent dengue DNA vaccine. The use of Vaxfectin(®) resulted in a significant increase in anti-dengue neutralizing antibody responses against dengue-1, -3 and -4. There was little to no effect on T cell responses as measured by interferon gamma ELISPOT assay. Animals immunized with the Vaxfectin(®)-formulated tetravalent DNA vaccine showed significant protection against live dengue-2 virus challenge compared to control animals (0.75 mean days of viremia vs 3.3 days). Animals vaccinated with nonadjuvanted DNA had a mean 2.0 days of viremia. These results support further evaluation of the Vaxfectin(®)-adjuvanted tetravalent dengue DNA vaccine in a Phase 1 clinical trial.

  11. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, In Ja [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Kim, Hee Cheol [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Nam Kyu [Section of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Hyeong-Rok [Department of Surgery, Chonnam National University Hwansun Hospital, Gwangju (Korea, Republic of); Kang, Sung-Bum [Department of Surgery, Seoul National University Bungdang Hospital, Bundang (Korea, Republic of); Choi, Gyu-Seog [Division of Colorectal Cancer Center, Kyungpook National University Medical Center, Daegu (Korea, Republic of); Lee, Kang Young [Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Seon-Hahn [Department of Surgery, Korea University Anam Hospital, Seoul (Korea, Republic of); Oh, Seung Taek [Department of Surgery, Seoul St. Mary Hospital, Catholic University, Seoul (Korea, Republic of); Lim, Seok-Byung; Kim, Jin Cheon [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Oh, Jae Hwan; Kim, Sun Young [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Lee, Woo Yong [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Jung Bok [Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Yu, Chang Sik, E-mail: csyu@amc.seoul.kr [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of)

    2015-07-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

  12. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Twu, Chih-Wen [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, Wen-Yi [Section of Basic Medicine, Department of Nursing, Hung Kuang University, Taichung, Taiwan (China); Chen, Chien-Chih [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Liang, Kai-Li; Jiang, Rong-San [Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wu, Ching-Te [Department of Radiation Oncology, Taichung Veterans General Hospital–Chiayi Branch, Chiayi, Taiwan (China); Shih, Yi-Ting [Department of Radiation Oncology, St. Martin De Porres Hospital, Chiayi, Taiwan (China); Lin, Po-Ju; Liu, Yi-Chun [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Lin, Jin-Ching, E-mail: jclin@vghtc.gov.tw [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine, China Medical University, Taichung, Taiwan (China)

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  13. Prognostic nomogram for patients with hepatocellular carcinoma underwent adjuvant transarterial chemoembolization following curative resection

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    Jing, Chu-Yu; Fu, Yi-Peng; Zheng, Su-Su; Yi, Yong; Shen, Hu-Jia; Huang, Jin-Long; Xu, Xin; Lin, Jia-Jia; Zhou, Jian; Fan, Jia; Ren, Zheng-Gang; Qiu, Shuang-Jian; Zhang, Bo-Heng

    2017-01-01

    Abstract Adjuvant transarterial chemoembolization (TACE) is a major option for postoperative hepatocellular carcinoma (HCC) patients with recurrence risk factors. However, individualized predictive models for subgroup of these patients are limited. This study aimed to develop a prognostic nomogram for patients with HCC underwent adjuvant TACE following curative resection. A cohort comprising 144 HCC patients who received adjuvant TACE following curative resection in the Zhongshan Hospital were analyzed. The nomogram was formulated based on independent prognostic indicators for overall survival (OS). The performance of the nomogram was evaluated by the concordance index (C-index), calibration curve, and decision curve analysis (DCA) and compared with the conventional staging systems. The results were validated in an independent cohort of 86 patients with the same inclusion criteria. Serum alpha-fetoprotein (AFP), hyper-sensitive C-reactive protein (hs-CRP), incomplete tumor encapsulation, and double positive staining of Cytokeratin 7 and Cytokeratin 19 on tumor cells were identified as independent predictors for OS. The C-indices of the nomogram for OS prediction in the training cohort and validation cohort were 0.787 (95%CI 0.775–0.799) and 0.714 (95%CI 0.695–0.733), respectively. In both the training and validation cohorts, the calibration plot showed good consistency between the nomogram-predicted and the observed survival. Furthermore, the established nomogram was superior to the conventional staging systems in terms of C-index and clinical net benefit on DCA. The proposed nomogram provided an accurate prediction on risk stratification for HCC patients underwent adjuvant TACE following curative resection. PMID:28296727

  14. Effect of adjuvant lithium on thyroxine (T4) concentration after radioactive iodine therapy

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    Hammond, Emmanuel NiiBoye; Vangu, Mboyo-Di-Tamba Heben Willy [University of the Witwatersrand, Division of Nuclear Medicine and Molecular Imaging, Department of Radiation Sciences, Johannesburg (South Africa)

    2016-10-15

    To study the effect of adjuvant lithium on serum thyroxine (T4) concentrations in patients treated with radioactive iodine (RAI) therapy in our environment. This was a prospective simple randomized comparative, experimental cohort study of patients with hyperthyroidism referred for RAI ablation therapy in the two main academic hospitals in Johannesburg between February 2014 and September 2015. Amongst the 163 participants in the final analysis, 75 received RAI alone and 88 received RAI with lithium. The difference in mean T4 concentrations at 3 months between the RAI-only group (17.67 pmol/l) and the RAI with lithium group (11.55 pmol/l) was significant with a small effect size (U = 2328.5, Z = -2.700, p = 0.007, r = 0.01). Significant decreases in T4 concentrations were observed as early as 1 month after RAI (p = 0.0001) in the RAI with lithium group, but in the RAI-only group, significant decreases in T4 concentrations were observed only at 3 months after RAI therapy (p = 0.000). Women and patients with Graves' disease who received RAI with adjuvant lithium also showed significant decreases in T4 concentrations at 1 month (p = 0.002 and p = 0.003, respectively). Adjuvant lithium leads to an earlier and better response to RAI therapy with lower T4 concentrations that are achieved earlier. This earlier response and decrease in T4 concentrations were noted in patients with Graves' disease and nodular goitre, and in women with hyperthyroidism who received adjuvant lithium therapy. (orig.)

  15. Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

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    McMillan, Matthew T. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Ojerholm, Eric [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Roses, Robert E., E-mail: Robert.Roses@uphs.upenn.edu [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Plastaras, John P.; Metz, James M. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Mamtani, Ronac [Department of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A. [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Stripp, Diana; Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Datta, Jashodeep [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States)

    2015-10-01

    Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

  16. A novel laser vaccine adjuvant increases the motility of antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Xinyuan Chen

    Full Text Available BACKGROUND: Development of a potent vaccine adjuvant without introduction of any side effects remains an unmet challenge in the field of the vaccine research. METHODOLOGY/PRINCIPAL FINDINGS: We found that laser at a specific setting increased the motility of antigen presenting cells (APCs and immune responses, with few local or systemic side effects. This laser vaccine adjuvant (LVA effect was induced by brief illumination of a small area of the skin or muscle with a nondestructive, 532 nm green laser prior to intradermal (i.d. or intramuscular (i.m. administration of vaccines at the site of laser illumination. The pre-illumination accelerated the motility of APCs as shown by intravital confocal microscopy, leading to sufficient antigen (Ag-uptake at the site of vaccine injection and transportation of the Ag-captured APCs to the draining lymph nodes. As a result, the number of Ag(+ dendritic cells (DCs in draining lymph nodes was significantly higher in both the 1° and 2° draining lymph nodes in the presence than in the absence of LVA. Laser-mediated increases in the motility and lymphatic transportation of APCs augmented significantly humoral immune responses directed against a model vaccine ovalbumin (OVA or influenza vaccine i.d. injected in both primary and booster vaccinations as compared to the vaccine itself. Strikingly, when the laser was delivered by a hair-like diffusing optical fiber into muscle, laser illumination greatly boosted not only humoral but also cell-mediated immune responses provoked by i.m. immunization with OVA relative to OVA alone. CONCLUSION/SIGNIFICANCE: The results demonstrate the ability of this safe LVA to augment both humoral and cell-mediated immune responses. In comparison with all current vaccine adjuvants that are either chemical compounds or biological agents, LVA is novel in both its form and mechanism; it is risk-free and has distinct advantages over traditional vaccine adjuvants.

  17. Advances in management of adjuvant chemotherapy in rectal cancer: Consequences for clinical practice.

    Science.gov (United States)

    Netter, Jeanne; Douard, Richard; Durdux, Catherine; Landi, Bruno; Berger, Anne; Taieb, Julien

    2016-11-01

    More than half the patients with rectal cancer present with locally advanced rectal disease at diagnosis with a high risk of recurrence. Preoperative chemoradiotherapy and standardized radical surgery with total mesorectal excision have been established as the 'gold standard' for treating these patients. Pathological staging using the ypTNM classification system to decide on adjuvant chemotherapy (ACT) is widely used in clinical practice, but the delivery of ACT is still controversial, as many discrepancies persist in the conclusions of different trials, due to heterogeneity of the inclusion criteria between studies, lack of statistical power, and variations in preoperative and adjuvant regimens. In 2014, a meta-analysis of four randomized phase-III trials (EORTC 22921, I-CNR-RT, PROCTOR-SCRIPT, CHRONICLE) failed to demonstrate any statistical efficacy of fluorouracil (5FU)-based ACT. Three recent randomized trials aimed to compare 5FU with 5FU plus oxaliplatin-based chemotherapy. Two of them (ADORE, CAO/ARO/AIO-04) appeared to find a disease-free survival benefit for patients treated with the combination therapy. Thus, while awaiting new data, it can be said that, as of 2015, patients with yp stage I tumors or histological complete response derived no benefit from adjuvant therapy. On the other hand, the FOLFOX chemotherapy regimen should be proposed for yp stage III patients, and may be considered for yp stage II tumors in fit patients with high-risk factors. Nevertheless, well-designed and sufficiently powered clinical trials dedicated to adjuvant treatments for rectal cancer remain justified in future to achieve a high level of proof in keeping with evidence-based medical standards.

  18. Development of a lipopolysaccharide (LPS)-supplemented adjuvant and its effects on cell-mediated and humoral immune responses in male rats immunized against sperm

    Science.gov (United States)

    NOGUCHI, Junko; WATANABE, Shinya; NGUYEN, Thanh Q. Dang; KIKUCHI, Kazuhiro; KANEKO, Hiroyuki

    2016-01-01

    Supplementation with lipopolysaccharide (LPS) from non-pathogenic Escherichia coli was found to enhance the adjuvant effects of a veterinary vaccine adjuvant (ISA 71VG®). Sperm immunization using 71VG as an adjuvant in the immature period induced infertility in 25% of male rats, whereas this increased to 62.5% after immunization with 71VG + LPS or Freund′s complete adjuvant (FCA). Mean testicular weight of non-sterile males in the 71VG + LPS group was significantly lower than that in the 71VG or FCA group. Histological examination of testicular tissue from sterile males demonstrated severe impairment of spermatogenesis due to experimental autoimmune orchitis, a cell-mediated autoimmune condition. The serum anti-sperm titer was elevated in the three sperm-immunized groups relative to male rats treated with adjuvant alone, but the titer was higher in the 71VG + LPS and FCA groups than in the 71VG group. We consider that this LPS-supplemented adjuvant stimulates both humoral and cell-mediated immune responses to an extent comparable to FCA. PMID:27890874

  19. Improving the Th1 cellular efficacy of the lead Yersinia pestis rF1-V subunit vaccine using SA-4-1BBL as a novel adjuvant.

    Science.gov (United States)

    Dinc, Gunes; Pennington, Jarrod M; Yolcu, Esma S; Lawrenz, Matthew B; Shirwan, Haval

    2014-09-03

    The lead candidate plague subunit vaccine is the recombinant fusion protein rF1-V adjuvanted with alum. While alum generates Th2 regulated robust humoral responses, immune protection against Yersinia pestis has been shown to also involve Th1 driven cellular responses. Therefore, the rF1-V-based subunit vaccine may benefit from an adjuvant system that generates a mixed Th1 and humoral immune response. We herein assessed the efficacy of a novel SA-4-1BBL costimulatory molecule as a Th1 adjuvant to improve cellular responses generated by the rF1-V vaccine. SA-4-1BBL as a single adjuvant had better efficacy than alum in generating CD4(+) and CD8(+) T cells producing TNFα and IFNγ, signature cytokines for Th1 responses. The combination of SA-4-1BBL with alum further increased this Th1 response as compared with the individual adjuvants. Analysis of the humoral response revealed that SA-4-1BBL as a single adjuvant did not generate a significant Ab response against rF1-V, and SA-4-1BBL in combination with alum did not improve Ab titers. However, the combined adjuvants significantly increased the ratio of Th1 regulated IgG2c in C57BL/6 mice to the Th2 regulated IgG1. Finally, a single vaccination with rF1-V adjuvanted with SA-4-1BBL+alum had better protective efficacy than vaccines containing individual adjuvants. Taken together, these results demonstrate that SA-4-1BBL improves the protective efficacy of the alum adjuvanted lead rF1-V subunit vaccine by generating a more balanced Th1 cellular and humoral immune response. As such, this adjuvant platform may prove efficacious not only for the rF1-V vaccine but also against other infections that require both cellular and humoral immune responses for protection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Outcomes after primary or adjuvant radiotherapy for salivary gland carcinoma.

    Science.gov (United States)

    Holtzman, Adam; Morris, Christopher G; Amdur, Robert J; Dziegielewski, Peter T; Boyce, Brian; Mendenhall, William M

    2017-03-01

    We report long-term outcomes of patients treated with primary radiotherapy (RT) or surgery and adjuvant RT for salivary gland malignancies. From 1964 to 2012, 291 patients received primary RT (n = 67) or RT combined with surgery (n = 224). The 5-, 10-, and 15-year local control, local-regional control, distant metastasis-free survival, cause-specific survival and overall survival rates were 82%, 77% and 73%; 77%, 72% and 67%; 74%, 70% and 70%; 70%, 59% and 54%; and 63%, 47% and 38%, respectively. Per multivariate analysis, combined surgery and RT and T stage impacted local control; overall stage and combined surgery and RT impacted local-regional control; overall stage impacted distant metastasis-free survival; and overall stage, node positivity, clinical nerve invasion, and surgery and RT impacted cause-specific and overall survival. Five percent of patients experienced grade 3 or worse toxicity. Combined surgery and RT improves local control, local-regional control, and cause-specific survival compared with primary RT for salivary tumors.

  1. Ketamine as an adjuvant to opioids for cancer pain.

    Science.gov (United States)

    Bell, Rae F; Eccleston, Christopher; Kalso, Eija A

    2017-06-28

    This is an update of a review first published in 2003 and updated in 2012.Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an adjuvant to opioids for the treatment of refractory cancer pain, when opioids alone or in combination with appropriate adjuvant analgesics prove to be ineffective. Ketamine is known to have psychomimetic (including hallucinogenic), urological, and hepatic adverse effects. To determine the effectiveness and adverse effects of ketamine as an adjuvant to opioids for refractory cancer pain in adults. For this update, we searched MEDLINE (OVID) to December 2016. We searched CENTRAL (CRSO), Embase (OVID) and two clinical trial registries to January 2017. The intervention considered by this review was the addition of ketamine, given by any route of administration, in any dose, to pre-existing opioid treatment given by any route and in any dose, compared with placebo or active control. We included studies with a group size of at least 10 participants who completed the trial. Two review authors independently assessed the search results and performed 'Risk of bias' assessments. We aimed to extract data on patient-reported pain intensity, total opioid consumption over the study period; use of rescue medication; adverse events; measures of patient satisfaction/preference; function; and distress. We also assessed participant withdrawal (dropout) from trial. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). One new study (185 participants) was identified by the updated search and included in the review. We included a total of three studies in this update.Two small studies, both with cross-over design, with 20 and 10 participants respectively, were eligible for inclusion in the original review. One study with 20 participants examined the addition of intrathecal ketamine to intrathecal morphine, compared with intrathecal morphine alone. The

  2. Adjuvant Radiation Therapy Improves Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma

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    Sabolch, Aaron [Department of Radiation Oncology, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Else, Tobias [Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Griffith, Kent A. [Center for Cancer Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Mchigan (United States); Ben-Josef, Edgar [Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Williams, Andrew [University of Michigan Medical School, Ann Arbor, Mchigan (United States); Miller, Barbra S. [Division of Endocrine Surgery, Department of General Surgery, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Worden, Francis [Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Hammer, Gary D. [Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Jolly, Shruti, E-mail: shrutij@med.umich.edu [Department of Radiation Oncology, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States)

    2015-06-01

    Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. Methods and Materials: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. Results: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Conclusions: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.

  3. A Randomized Multicentre Phase II Trial Comparing Adjuvant Therapy in Patients with Interferon Alpha-2b and 5-FU Alone or in Combination with Either External Radiation Treatment and Cisplatin (CapRI or Radiation alone regarding Event-Free Survival – CapRI-2

    Directory of Open Access Journals (Sweden)

    Friess Helmut

    2009-05-01

    Full Text Available Abstract Background The 5-year survival of patients with resected pancreatic adenocarcinoma is still unsatisfying. The ESPAC-1 and the CONKO 001 trial proofed that adjuvant chemotherapy improves 5-year survival significantly from approximately 14% to 21%. In parallel, investigators from the Virginia Mason Clinic reported a 5-year survival rate of 55% in a phase II trial evaluating a combination of adjuvant chemotherapy, immunotherapy and external beam radiation (CapRI-scheme. Two other groups confirmed in phase II trials these results to a certain extent. However, these groups reported severe gastrointestinal toxicity (up to 93% grade 3 or 4 toxicity. In a randomized controlled phase III trial, called CapRI, 110 patients were enrolled from 2004 to 2007 in Germany and Italy to check for reproducibility. Interestingly, much less gastrointestinal toxicity was observed. However, dose-reduction due to haematological side effects had to be performed in nearly all patients. First clinical results are expected for the end of 2009. Methods/Design CapRI-2 is an open, controlled, prospective, randomized, multicentre phase II trial with three parallel arms. A de-escalation of the CapRI-scheme will be tested in two different modifications. Patients in study arm A will be treated as outpatients with the complete CapRI-scheme consisting of cisplatin, Interferon alpha-2b and external beam radiation and three cycles of 5-fluorouracil continuous infusion. In study arm B the first de-escalation will be realised by omitting cisplatin. Next, patients in study arm C will additionally not receive external beam radiation. A total of 135 patients with pathologically confirmed R0 or R1 resected pancreatic adenocarcinoma are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to six-month event-free-survival. An event is defined as grade 3 or grade 4 toxicity, objective tumour recurrence, or death. Discussion The aim of this

  4. Gamma-irradiated influenza A virus provides adjuvant activity to a co-administered poorly immunogenic SFV vaccine in mice.

    Directory of Open Access Journals (Sweden)

    Rachelle eBabb

    2014-06-01

    Full Text Available Many currently available inactivated vaccines require 'adjuvants' to maximise the protective immune responses generated against the antigens of interest. Recent studies in mice with gamma-irradiated influenza A virus (γ-FLU have shown its superior efficacy compared to other forms of inactivated FLU vaccines and its ability to induce both potent type-I interferon (IFN-I responses and the IFN-I associated partial lymphocyte activation. Commonly, IFN-I responses induced by adjuvants, combined in vaccine preparations, have been shown to effectively enhance the immunogenicity of the antigens of interest. Therefore, we investigated the potential adjuvant activity of γ-FLU and the possible effect on antibody responses against co-administrated antigens, using gamma-irradiated Semliki Forest Virus (γ-SFV as the experimental vaccine in mice. Our data show that co-vaccination with γ-FLU and γ-SFV resulted in enhanced SFV-specific antibody responses in terms of increased titres by 6 fold and greater neutralisation efficacy, when compared to vaccination with γ-SFV alone. This study provides promising evidence related to the possible use of γ-FLU as an adjuvant to poorly immunogenic vaccines without compromising the vaccine efficacy of γ-FLU.

  5. Endogenous oils derived from human adipocytes are potent adjuvants that promote IL-1α-dependent inflammation.

    Science.gov (United States)

    Tynan, Graham A; Hearnden, Claire H; Oleszycka, Ewa; Lyons, Claire L; Coutts, Graham; O'Connell, Jean; Corrigan, Michelle A; Lynch, Lydia; Campbell, Matthew; Callanan, John J; Mok, Kenneth H; Geoghegan, Justin; O'Farrelly, Cliona; Allan, Stuart M; Roche, Helen M; O'Shea, Donal B; Lavelle, Ed C

    2014-06-01

    Obesity is characterized by chronic inflammation associated with neutrophil and M1 macrophage infiltration into white adipose tissue. However, the mechanisms underlying this process remain largely unknown. Based on the ability of oil-based adjuvants to induce immune responses, we hypothesized that endogenous oils derived from necrotic adipocytes may function as an immunological "danger signal." Here we show that endogenous oils of human origin are potent adjuvants, enhancing antibody responses to a level comparable to Freund's incomplete adjuvant. The endogenous oils were capable of promoting interleukin (IL)-1α-dependent recruitment of neutrophils and M1-like macrophages, while simultaneously diminishing M2-like macrophages. We found that endogenous oils from subcutaneous and omental adipocytes, and from healthy and unhealthy obese individuals, promoted comparable inflammatory responses. Furthermore, we also confirmed that white adipocytes in visceral fat of metabolically unhealthy obese (MUO) individuals are significantly larger than those in metabolically healthy obese individuals. Since adipocyte size is positively correlated with adipocyte death, we propose that endogenous oils have a higher propensity to be released from hypertrophied visceral fat in MUO individuals and that this is the key factor in driving inflammation. In summary, this study shows that adipocytes contain a potent oil adjuvant which drives IL-1α-dependent proinflammatory responses in vivo.

  6. Environmental adjuvants, apoptosis and the censorship over autoimmunity.

    Science.gov (United States)

    Rovere-Querini, Patrizia; Manfredi, Angelo A; Sabbadini, Maria Grazia

    2005-11-01

    Alterations during apoptosis lead to the activation of autoreactive T cells and the production of autoantibodies. This article discusses the pathogenic potential of cells dying in vivo, dissecting the role of signals that favor immune responses (adjuvants) and the influence of genetic backgrounds. Diverse factors determine whether apoptosis leads or not to a self-sustaining, clinically apparent autoimmune disease. The in vivo accumulation of uncleared dying cells per se is not sufficient to cause disease. However, dying cells are antigenic and their complementation with immune adjuvants causes lethal diseases in predisposed lupus-prone animals. At least some adjuvant signals directly target the function and the activation state of antigen presenting cells. Several laboratories are aggressively pursuing the molecular identification of endogenous adjuvants. Sodium monourate and the high mobility group B1 protein (HMGB1) are, among those identified so far, well known to rheumatologists. However, even the complementation of apoptotic cells with potent adjuvant signals fail to cause clinical autoimmunity in most strains: autoantibodies generated are transient, do not undergo to epitope/spreading and do not cause disease. Novel tools for drug development will derive from the molecular identification of the constraints that prevent autoimmunity in normal subjects.

  7. Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

    Science.gov (United States)

    Mohan, Teena; Verma, Priyanka; Rao, D Nageswara

    2013-11-01

    The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

  8. Nanoparticulate Adjuvants and Delivery Systems for Allergen Immunotherapy

    Directory of Open Access Journals (Sweden)

    Juliana De Souza Rebouças

    2012-01-01

    Full Text Available In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  9. Optimizing Adherence to Adjuvant Imatinib in Gastrointestinal Stromal Tumor

    Science.gov (United States)

    Tetzlaff, Eric D.; Davey, Monica P.

    2013-01-01

    The increasing use of patient-administered oral anticancer drugs is paralleled by new challenges in maintaining treatment adherence. These challenges are particularly significant with adjuvant therapies for prevention of disease recurrence, where the benefits of ongoing treatment are not readily apparent to patients. Nurse practitioners and physician assistants (collectively referred to as advanced practitioners) play integral roles in providing education on disease and treatment to patients that can increase adherence to oral therapies and ideally improve outcomes. For patients with gastrointestinal stromal tumor (GIST), the oral targeted therapy imatinib has become the mainstay of treatment for advanced and recurrent disease and as adjuvant therapy following surgical resection. Recent data indicate significantly improved overall survival with 3 years vs. 1 year of adjuvant imatinib therapy. Continuous dosing with imatinib is needed for optimal efficacy and to limit additional health-care costs associated with management of disease progression in GIST. However, longer duration of therapy increases the risk of nonadherence. Imatinib adherence rates, as well as factors contributing to nonadherence to adjuvant therapy in routine clinical practice, are discussed in this review. Also explored are practical approaches for improving adherence to adjuvant imatinib therapy through greater patient education, in light of the increased duration of therapy in select patients. PMID:25032004

  10. Regulatory considerations on new adjuvants and delivery systems.

    Science.gov (United States)

    Sesardic, D

    2006-04-12

    New and improved vaccines and delivery systems are increasingly being developed for prevention, treatment and diagnosis of human diseases. Prior to their use in humans, all new biological products must undergo pre-clinical evaluation. These pre-clinical studies are important not only to establish the biological properties of the material and to evaluate its possible risk to the public, but also to plan protocols for subsequent clinical trials from which safety and efficacy can be evaluated. For vaccines, evaluation in pre-clinical studies is particularly important as information gained may also contribute to identifying the optimum composition and formulation process and provide an opportunity to develop suitable indicator tests for quality control. Data from pre-clinical and laboratory evaluation studies, which continue during clinical studies, is used to support an application for marketing authorisation. Addition of a new adjuvant and exploration of new delivery systems for vaccines presents challenges to both manufacturers and regulatory authorities. Because no adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine, pre-clinical and appropriate toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/vaccine combination. Current regulatory requirements for the pharmaceutical and pre-clinical safety assessment of vaccines are insufficient and initiatives are in place to develop more specific guidelines for evaluation of adjuvants in vaccines.

  11. Nanoparticulate adjuvants and delivery systems for allergen immunotherapy.

    Science.gov (United States)

    De Souza Rebouças, Juliana; Esparza, Irene; Ferrer, Marta; Sanz, María Luisa; Irache, Juan Manuel; Gamazo, Carlos

    2012-01-01

    In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  12. Adjuvants for Clostridium tetani and Clostridium diphtheriae vaccines updating.

    Science.gov (United States)

    Alshanqiti, Fatimah M; Al-Masaudi, Saad B; Al-Hejin, Ahmed M; Redwan, Elrashdy M

    2017-01-01

    It's known that diphtheria and tetanus are a contagious lethal diseases over the years, they caused by pathogenic microbes corynebacterium diphtheria and Clostridium tetani, respectively. The diseases result from the production of bacterial toxin. Vaccination with bacterial toxoid vaccines adsorbed on particulates adjuvants still are the best way to prevent this epidemic diseases from spread. The particulate vaccines have been shown to be more efficient than soluble one for the induction of the immune responses. Nanoparticles can be engineered to enhance the immune responses. As well known the immune response to inactivate killed and subunit vaccine enhances by alum adjuvants. The adjuvants examined and tested after reducing its size to particle size, thus mimic size of viruses which is considered smallest units can derive the immune system. The major issue is minimizing the adjuvant particles, to gain insight of resulting immunity types and impact on immune response. The adjuvant effect of micro/nanoparticles appears to largely be a consequence of their uptake into antigen presenting cells.

  13. Functionalized graphene oxide serves as a novel vaccine nano-adjuvant for robust stimulation of cellular immunity

    Science.gov (United States)

    Xu, Ligeng; Xiang, Jian; Liu, Ye; Xu, Jun; Luo, Yinchan; Feng, Liangzhu; Liu, Zhuang; Peng, Rui

    2016-02-01

    Benefiting from their unique physicochemical properties, graphene derivatives have attracted great attention in biomedicine. In this study, we carefully engineered graphene oxide (GO) as a vaccine adjuvant for immunotherapy using urease B (Ure B) as the model antigen. Ure B is a specific antigen for Helicobacter pylori, which is a class I carcinogen for gastric cancer. Polyethylene glycol (PEG) and various types of polyethylenimine (PEI) were used as coating polymers. Compared with single-polymer modified GOs (GO-PEG and GO-PEI), certain dual-polymer modified GOs (GO-PEG-PEI) can act as a positive modulator to promote the maturation of dendritic cells (DCs) and enhance their cytokine secretion through the activation of multiple toll-like receptor (TLR) pathways while showing low toxicity. Moreover, this GO-PEG-PEI can serve as an antigen carrier to effectively shuttle antigens into DCs. These two advantages enable GO-PEG-PEI to serve as a novel vaccine adjuvant. In the subsequent in vivo experiments, compared with free Ure B and clinically used aluminum-adjuvant-based vaccine (Alum-Ure B), GO-PEG-PEI-Ure B induces stronger cellular immunity via intradermal administration, suggesting promising applications in cancer immunotherapy. Our work not only presents a novel, highly effective GO-based vaccine nano-adjuvant, but also highlights the critical roles of surface chemistry for the rational design of nano-adjuvants.Benefiting from their unique physicochemical properties, graphene derivatives have attracted great attention in biomedicine. In this study, we carefully engineered graphene oxide (GO) as a vaccine adjuvant for immunotherapy using urease B (Ure B) as the model antigen. Ure B is a specific antigen for Helicobacter pylori, which is a class I carcinogen for gastric cancer. Polyethylene glycol (PEG) and various types of polyethylenimine (PEI) were used as coating polymers. Compared with single-polymer modified GOs (GO-PEG and GO-PEI), certain dual

  14. Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin

    Institute of Scientific and Technical Information of China (English)

    Yan-li LIU; Hai-ming LIN; Rong ZOU; Jun-chao WU; Rong HAN; Laurence N RAYMOND; Paul F REID; Zheng-hong QIN

    2009-01-01

    Aim:Cobratoxin (CTX),the long-chain α-neurotoxin from Thailand cobra venom,has been demonstrated to have analgesic action in rodent pain models.The present study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on adju-vant arthritis (AA) in rats.Methods: Arthritis was induced by injection of complete Freund's adjuvant (CFA) in rats.Paw swelling and hyperalgesia of AA rats were measured at various times after CFA administration.Tumor necrosis factor-a (TNF-α),interleukin-1 (IL-1),interleukin-2 (IL-2) and interleukin-10 (IL-10) levels in serum were determined with ELISA.Histopathological changes in synoviocytes were examined under a microscope.Involvement of the cholinergic system in the effects of CTX was examinedby pretreatment of animals with the α7 nicotinic receptor (α7-nAChR) antagonist methyllycaconitine (MLA).Results: CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal.The lev-els of TNF-α,IL-1 and IL-2 in the serum of AA rats were increased,whereas the level of IL-10 was decreased.Histopathologi-cal examination of synoviocytes showed pronounced inflammation and accumulation of collagen.The administration of CTX (17.0 μg/kg,ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia.CTX also reduced the produc-tion ofTNF-α,IL-1,and IL-2 but increased the production of IL-10 and altered pathohistological changes.The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by MLA (3 mg/kg,sc).Conclusion: These results indicate that CTX has a beneficial effect on CFA-induced arthritis by modulating the production of inflammatory cytokines,α7-nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX.

  15. Health-related quality of life in patients with high-risk melanoma randomised in the Nordic phase 3 trial with adjuvant intermediate-dose interferon alfa-2b

    DEFF Research Database (Denmark)

    Brandberg, Y; Aamdal, S; Bastholt, Lars;

    2012-01-01

    To compare health-related quality of life (HRQoL) and side-effects in patients with high-risk melanoma participating in a randomised phase III trial of adjuvant interferon alfa-2b (IFN).......To compare health-related quality of life (HRQoL) and side-effects in patients with high-risk melanoma participating in a randomised phase III trial of adjuvant interferon alfa-2b (IFN)....

  16. Adjuvant chemo-radiotherapy in the "sandwich" method for high risk endometrial cancer--a review of literature.

    Science.gov (United States)

    Bie, Yachun; Zhang, Zhenyu; Wang, Xiaolan

    2015-06-24

    Endometrial cancer is a common female malignancy. Patients with high-risk endometrial cancer have relatively high incidence of metastasis and recurrence. Despite complete resection, patients with stage III or IV are at high risk of local or distant recurrence. Systemic adjuvant treatment includes chemotherapy and radiotherapy. But the optimal scheduling is not known. Recently proposed sequential chemo-radiotherapy as sandwich therapy for high risk endometrial cancer have yielded encouraging results. This article is to review the adjuvant chemo-radiotherapy in the "sandwich" method for high risk endometrial cancer to help clinicians identify the most effective adjuvant treatment for patients with high risks of it. We used MEDLINE, EMBASE, Cochrane Library and CBM databases to search the literature. A systematic review was made. And most data showed "sandwich" therapy is feasible, efficacious, well-tolerated and resulted in excellent long-term progression free and overall survival in the setting of advanced endometrial cancer. Randomized trials are necessary to compare chemo-radio therapy given in the "sandwich" fashion to other means of sequencing these treatment modalities. It is also necessary to define which population is best suited for "sandwich" adjuvant therapy.

  17. A dual TLR agonist adjuvant enhances the immunogenicity and protective efficacy of the tuberculosis vaccine antigen ID93.

    Science.gov (United States)

    Orr, Mark T; Beebe, Elyse A; Hudson, Thomas E; Moon, James J; Fox, Christopher B; Reed, Steven G; Coler, Rhea N

    2014-01-01

    With over eight million cases of tuberculosis each year there is a pressing need for the development of new vaccines against Mycobacterium tuberculosis. Subunit vaccines consisting of recombinant proteins are an attractive vaccine approach due to their inherent safety compared to attenuated live vaccines and the uniformity of manufacture. Addition of properly formulated TLR agonist-containing adjuvants to recombinant protein vaccines enhances the antigen-specific CD4(+) T cell response characterized by IFN-γ and TNF, both of which are critical for the control of TB. We have developed a clinical stage vaccine candidate consisting of a recombinant fusion protein ID93 adjuvanted with the TLR4 agonist GLA-SE. Here we examine whether ID93+GLA-SE can be improved by the addition of a second TLR agonist. Addition of CpG containing DNA to ID93+GLA-SE enhanced the magnitude of the multi-functional TH1 response against ID93 characterized by co-production of IFN-γ, TNF, and IL-2. Addition of CpG also improved the protective efficacy of ID93+GLA-SE. Finally we demonstrate that this adjuvant synergy between GLA and CpG is independent of TRIF signaling, whereas TRIF is necessary for the adjuvant activity of GLA-SE in the absence of CpG.

  18. A dual TLR agonist adjuvant enhances the immunogenicity and protective efficacy of the tuberculosis vaccine antigen ID93.

    Directory of Open Access Journals (Sweden)

    Mark T Orr

    Full Text Available With over eight million cases of tuberculosis each year there is a pressing need for the development of new vaccines against Mycobacterium tuberculosis. Subunit vaccines consisting of recombinant proteins are an attractive vaccine approach due to their inherent safety compared to attenuated live vaccines and the uniformity of manufacture. Addition of properly formulated TLR agonist-containing adjuvants to recombinant protein vaccines enhances the antigen-specific CD4(+ T cell response characterized by IFN-γ and TNF, both of which are critical for the control of TB. We have developed a clinical stage vaccine candidate consisting of a recombinant fusion protein ID93 adjuvanted with the TLR4 agonist GLA-SE. Here we examine whether ID93+GLA-SE can be improved by the addition of a second TLR agonist. Addition of CpG containing DNA to ID93+GLA-SE enhanced the magnitude of the multi-functional TH1 response against ID93 characterized by co-production of IFN-γ, TNF, and IL-2. Addition of CpG also improved the protective efficacy of ID93+GLA-SE. Finally we demonstrate that this adjuvant synergy between GLA and CpG is independent of TRIF signaling, whereas TRIF is necessary for the adjuvant activity of GLA-SE in the absence of CpG.

  19. Surgical outcomes after excision of pigmented villonodular synovitis localized to the ankle and hindfoot without adjuvant therapy.

    Science.gov (United States)

    Sung, Ki-Sun; Ko, Kyung Rae

    2015-01-01

    Although a benign disorder, pigmented villonodular synovitis (PVNS) has a high rate of recurrence. Because of the high incidence of recurrence and concern about destruction of the affected joint, several adjuvant therapies have been promoted without a clear standard treatment strategy. We reviewed cases of PVNS affecting the ankle and hindfoot joints (ankle and/or subtalar joints) treated with surgical resection without adjuvant therapy in an effort to identify the incidence of PVNS recurrence after excision without adjuvant therapy. Of the 10 cases with a mean follow-up duration of 33.2 ± 19.8 months, 4 (40%) developed a recurrence, with a mean interval of 6 (range 3 to 14) months. At the final follow-up visit, the mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score was 86.6 ± 12. The clinical outcomes of PVNS affecting the ankle and hindfoot joints are associated with a relatively high incidence of recurrence, and additional clinical investigation comparing the incidence of recurrence in patients undergoing excision versus excision with adjuvant therapy is needed for us to better understand this condition and provide more informed recommendations to our patients.

  20. Induction of the 'ASIA' syndrome in NZB/NZWF1 mice after injection of complete Freund's adjuvant (CFA).

    Science.gov (United States)

    Bassi, N; Luisetto, R; Del Prete, D; Ghirardello, A; Ceol, M; Rizzo, S; Iaccarino, L; Gatto, M; Valente, M L; Punzi, L; Doria, A

    2012-02-01

    Adjuvants, commonly used in vaccines, may be responsible for inducing autoimmunity and autoimmune diseases, both in humans and mice. The so-called 'ASIA' (Autoimmune/inflammatory Syndrome Induced by Adjuvants) syndrome has been recently described, which is caused by the exposure to a component reproducing the effect of adjuvants. The aim of our study was to evaluate the effect of injection of complete Freund's adjuvant (CFA) in NZB/NZWF1 mice, a lupus-prone murine model. We injected 10 NZB/NZWF1 mice with CFA/PBS and 10 with PBS, three times, 3 weeks apart, and followed-up until natural death. CFA-injected mice developed both anti-double-stranded DNA and proteinuria earlier and at higher levels than the control group. Proteinuria-free survival rate and survival rate were significantly lower in CFA-treated mice than in the control mice (p = 0.002 and p = 0.001, respectively). Histological analyses showed a more severe glomerulonephritis in CFA-injected mice compared with the control mice. In addition, lymphoid hyperplasia in spleen and lungs, myocarditis, and vasculitis were observed in the former, but not in the latter group. In conclusion, the injection of CFA in NZB/NZWF1 mice accelerated autoimmune manifestations resembling 'ASIA' syndrome in humans.

  1. The immunobiology of aluminium adjuvants: how do they really work?

    Science.gov (United States)

    Exley, Christopher; Siesjö, Peter; Eriksson, Håkan

    2010-03-01

    Aluminium adjuvants potentiate the immune response, thereby ensuring the potency and efficacy of typically sparingly available antigen. Their concomitant critical importance in mass vaccination programmes may have prompted recent intense interest in understanding how they work and their safety. Progress in these areas is stymied, however, by a lack of accessible knowledge pertaining to the bioinorganic chemistry of aluminium adjuvants, and, consequently, the inappropriate application and interpretation of experimental models of their mode of action. The objective herein is, therefore, to identify the many ways that aluminium chemistry contributes to the wide and versatile armoury of its adjuvants, such that future research might be guided towards a fuller understanding of their role in human vaccinations.

  2. The adjuvant activity of alphavirus replicons is enhanced by incorporating the microbial molecule flagellin into the replicon.

    Directory of Open Access Journals (Sweden)

    Maria L Knudsen

    Full Text Available Ligands of pattern recognition receptors (PRRs including Toll-like receptors (TLRs stimulate innate and adaptive immune responses and are considered as potent adjuvants. Combinations of ligands might act in synergy to induce stronger and broader immune responses compared to stand-alone ligands. Alphaviruses stimulate endosomal TLRs 3, 7 and 8 as well as the cytoplasmic PRR MDA-5, resulting in induction of a strong type I interferon (IFN response. Bacterial flagellin stimulates TLR5 and when delivered intracellularly the cytosolic PRR NLRC4, leading to secretion of proinflammatory cytokines. Both alphaviruses and flagellin have independently been shown to act as adjuvants for antigen-specific antibody responses. Here, we hypothesized that alphavirus and flagellin would act in synergy when combined. We therefore cloned the Salmonella Typhimurium flagellin (FliC gene into an alphavirus replicon and assessed its adjuvant activity on the antibody response against co-administered antigen. In mice immunized with recombinant alphavirus, antibody responses were greatly enhanced compared to soluble FliC or control alphavirus. Both IgG1 and IgG2a/c responses were increased, indicating an enhancement of both Th1 and Th2 type responses. The adjuvant activity of FliC-expressing alphavirus was diminished but not abolished in the absence of TLR5 or type I IFN signaling, suggesting the contribution of several signaling pathways and some synergistic and redundant activity of its components. Thus, we have created a recombinant adjuvant that stimulates multiple signaling pathways of innate immunity resulting in a strong and broad antibody response.

  3. Esculetin reduces leukotriene B4 level in plasma of rats with adjuvant-induced arthritis

    Directory of Open Access Journals (Sweden)

    Przemysław Rzodkiewicz

    2016-10-01

    Full Text Available Objectives : Esculetin (6,7-dihydroxycoumarin is a natural coumarin with anti-oxidant, anti-inflammatory and anti-nociceptive activity. It acts as a potent inhibitor of lipoxygenases (5-LOX and 12-LOX and decreases the production of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9. Because both inhibition of lipoxygenases and inhibition of matrix metalloproteinases are effective strategies in the treatment of rheumatoid arthritis, we investigated whether esculetin may be effective in adjuvant-induced arthritis in rats. Material and methods : The study was performed on male Lewis rats, in the adjuvant-induced arthritis model. Rats were divided into two groups: control (treated with 1% methylcellulose and experimental (treated with esculetin – 10 mg/kg ip.. The tested compound was administered for 5 consecutive days starting on the 21st day after induction of arthritis. Each group consisted of 7 animals. After 5 days of treatment, rats were anesthetized. The concentration of leukotriene B4 (LTB4 in plasma was determined by a competitive enzyme immunoassay. Results : The LTB4 level in plasma of rats with adjuvant-induced arthritis is increased in comparison to rats without inflammation (362 ±34 vs. 274 ±15 pg/ml, p < 0.01, respectively. Five-day treatment with esculetin in adjuvant-induced arthritis rats decreases the LTB4 level to a level comparable with rats without inflammation (284 ±23 pg/ml, p < 0.01. Conclusions : LTB4 is the most potent chemotactic agent influencing neutrophil migration into the joint. It is known that its level in serum of patients with active rheumatoid arthritis is increased and correlates with disease severity. Some other lipoxygenase inhibitors have already been tested as potential drug candidates in clinical and preclinical trials for rheumatoid arthritis (Zileuton, PF-4191834. Because esculetin decreases the LTB4 level in plasma of rats in adjuvant-induced arthritis, it may also be considered as an attractive

  4. Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Morganti, Alessio G. [Department of Radiotherapy, Università Cattolica S. Cuore, Rome (Italy); Unit of Radiotherapy, Unit of General Oncology, Fondazione Giovanni Paolo II, Campobasso (Italy); Falconi, Massimo [Department of Surgery, University of Verona, Verona (Italy); Stiphout, Ruud G.P.M. van [Department of Radiation Oncology (MAASTRO), GROW, University Medical Centre Maastricht (Netherlands); Mattiucci, Gian-Carlo, E-mail: gcmattiucci@rm.unicatt.it [Department of Radiotherapy, Università Cattolica S. Cuore, Rome (Italy); Alfieri, Sergio [Department of Surgery, Università Cattolica S. Cuore, Rome (Italy); Calvo, Felipe A. [Department of Oncology, Hospital General Universitario Gregorio Marañón, Complutense University, Madrid (Spain); Dubois, Jean-Bernard [Département de Radiothérapie, CRLC, Montpellier Cedex (France); Fastner, Gerd [Department of Radiotherapy, PMU, Salzburg (Austria); Herman, Joseph M. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Maidment, Bert W. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Miller, Robert C. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Reni, Michele [Department of Oncology, S. Raffaele Scientific Institute, Milan (Italy); Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Ippolito, Edy [Department of Radiation Oncology, University Campus Biomedico, Roma (Italy); and others

    2014-11-15

    Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.

  5. Oral administration of bovine whey proteins to mice elicits opposing immunoregulatory responses and is adjuvant dependent

    Science.gov (United States)

    AFUWAPE, A O; TURNER, M W; STROBEL, S

    2004-01-01

    Most studies investigating the induction of oral tolerance (OT) use purified proteins such as ovalbumin (OVA), bovine serum albumin (BSA) and beta-lactoglobulin (β-LG). Little information is available regarding the induction of OT to a protein mixture, e.g. cow's milk. In this study we compared the regulatory mechanisms induced after the oral administration of a whey protein concentrate (WP) derived from cow's milk following immunization with two different adjuvants, complete Freund's adjuvant (CFA) and alum. OVA was used as a control antigen. Animals were given a single feed of these proteins at an equivalent dose of 1 mg/g body weight before they were immunized seven days later with the antigen in Freund's adjuvant or alum. Delayed type hypersensitivity (DTH) responses were suppressed by both a feed of WP and OVA after immunization with CFA. However, only OVA feeding suppressed antigen specific IgG responses. In an attempt to investigate whether WP would tolerize the more susceptible IgE responses, alum immunization replaced CFA as the adjuvant used for systemic immunizations. WP, after a single feed, significantly primed for DTH and IgE responses indicating oral sensitization to WP. In contrast, OVA suppressed DTH, IgE and IgG responses. Antigen specific proliferation of mononuclear cells was suppressed in mice fed OVA, but primed in those fed with WP. In addition cells taken from sensitized mice fed WP up-regulated levels of specific interleukin (IL) -4, -10 and -12 in vitro whereas these cytokines were suppressed in cultures from tolerant WP fed mice. Global suppression was obtained in cultures from tolerant OVA fed mice. TGF-β was not detected in draining PLN cell cultures of either tolerant or sensitized mice. These data suggest that a whey protein mixture induces divergent responses following immunization with either CFA or alum despite being fed at an identical dose. We suggest that that the choice of the adjuvant may determine the immunoregulatory

  6. Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica.

    Science.gov (United States)

    Rivera, Francheska; Espino, Ana M

    2016-01-01

    Fasciola hepatica saposin-like protein-2 (FhSAP2) is a protein differentially expressed in various developmental stages of F. hepatica. Recombinant FhSAP2 has demonstrated the induction of partial protection in mice and rabbits when it is administered subcutaneously (SC) in Freund's adjuvant. Because FhSAP2 is overexpressed in bacteria in the form of inclusion bodies (IBs), we isolated IBs expressing FhSAP2 and tested their immunogenicity when administered SC in mice emulsified in two different adjuvants: QS-21 and Montanide TM ISA720. Animals received three injections containing 20 μg of protein two weeks apart and 4 weeks after the third injection, mice were infected with 10 F. hepatica metacercariae by oral route. The percentages of protection induced by FhSAP2-IBs were estimated to be between 60.0 and 62.5% when compared with adjuvant-vaccinated, infected controls. By determining the levels of IgG1 and IgG2a antibodies and IL-4 and IFNγ cytokines in the serum of experimental animals, it was found that both Th1 and Th2 immune responses were significantly increased in the FhSAP2-IBs vaccinated groups compared with the adjuvant-vaccinated, infected control groups. The adjuvant-vaccinated groups had significantly lower IgG1 to IgG2a ratios and lower IL-4 to IFNγ ratios than the FhSAP2-IBs vaccinated animals, which is indicative of higher levels of Th2 immune responses. Irrespective to the adjuvant used, animals vaccinated with FhSAP2-IBs exhibited significantly higher survival percentage and less liver damage than the adjuvant-control groups. This study suggests that FhSAP2 has potential as vaccine against F. hepatica and that the protection elicited by this molecule could be linked to a mechanism driven by the CD4-Th1 cells.

  7. Neisseria lactamica antigens complexed with a novel cationic adjuvant

    OpenAIRE

    Gaspar, Emanuelle B.; Rosetti, Andreza S.; Lincopan, Nilton; De Gaspari, Elizabeth

    2013-01-01

    Colonization of the nasopharynx by non-pathogenic Neisseria species, including N. lactamica, has been suggested to lead to the acquisition of natural immunity against Neisseria meningitidis in young children. The aim of this study was to identify a model complex of antigens and adjuvant for immunological preparation against N. meningitidis B, based on cross reactivity with N. lactamica outer membrane vesicles (OMV) antigens and the (DDA-BF) adjuvant. Complexes of 25 µg of OMV in 0.1 mM of DDA...

  8. Aluminium: a natural adjuvant in Leishmania transmission via sand flies?

    Science.gov (United States)

    Maingon, Rhayza; Khela, Amandeep; Sampson, Christopher; Ward, Richard; Walker, Karen; Exley, Christopher

    2008-11-01

    Genetically identical Leishmania chagasi/infantum parasites cause both atypical cutaneous leishmaniasis and visceral leishmaniasis. In this report we have tested the first part of a hypothesis that states that the form of this disease that is manifested depends upon the adjuvant-like activity of aluminium of dietary origin accumulated in the salivary gland of the sand fly vector. In sand flies fed aluminium-supplemented sucrose we have used histochemistry to qualitatively identify aluminium in their salivary glands and graphite furnace atomic absorption spectrometry to quantify the aluminium content of dissected salivary glands. Aluminium may be acting as a natural adjuvant in some forms of leishmaniasis.

  9. A comparison of dexamethasone and clonidine as an adjuvant for caudal blocks in pediatric urogenital surgeries

    Science.gov (United States)

    Sinha, Chandni; Kumar, Bindey; Bhadani, Umesh Kumar; Kumar, Ajeet; Kumar, Amarjeet; Ranjan, Alok

    2016-01-01

    Background: Caudal block is a reliable regional analgesic technique for pediatric urogenital surgeries. Various adjuvants have been tried to enhance the duration of action of bupivicaine. Though clonidine is extensively used as an adjuvant in caudal anaesthesia, it can have troublesome adverse effects like bradycardia, hypotension and sedation. Lately dexamethasone has become popular as an adjuvant in paediatric caudals due to its safety profile. Aim: The aim of this study was to compare dexamethasone and clonidine coadministered with bupivicaine caudally in paediatric patients undergoing urogenital surgeries in terms of analgesia and adverse effects. Settings and Design: Prospective, double blinded randomised study. Subjects and Method: Sixty American Society of Anesthesiologists physical status I and II children, aged 1-6 years undergoing urogenital surgeries were allocated in 2 groups: Group I: 0.5 mL.kg−1 of 0.25% bupivicaine with dexamethasone 0.1 mg.kg−1 in 1 ml normal saline (NS) Group II: 0.5 mL.kg−1 of 0.25% bupivicaine with clonidine 1 μg.kg−1 diluted in 1 ml normal saline. The parameters studied included duration of analgesia, intraoperative and postoperative hemodynamics, sedation scores and incidence of adverse effects like wound dehiscence, bleeding, vomiting and respiratory depression. Statistical Analysis Used: Statistical analysis was carried out using Stata Version 10. After checking for the normality assumption, t-test for comparing means of two independent samples was used for comparing baseline continuous variables. P values <0.05 were considered significant. Results: Patients in Group II had longer duration of analgesia postoperatively. Patients in this group also had lower heart rate and more sedation scores. Conclusion: Our study shows that caudal dexamethasone is a good alternative to clonidine with more stable hemodynamics and lesser sedation scores in the immediate postoperative period. Both the drugs offer good analgesia

  10. Influenza vaccination in children primed with MF59®-adjuvanted or non-adjuvanted seasonal influenza vaccine

    Science.gov (United States)

    Vesikari, Timo; Forstén, Aino; Arora, Ashwani; Tsai, Theodore; Clemens, Ralf

    2015-01-01

    Routine annual influenza immunization is increasingly recommended in young children. We compared the safety and immunogenicity of vaccination with trivalent inactivated influenza vaccine (TIV) versus MF59-adjuvanted TIV (aTIV) in children who received 2 half or full doses of aTIV or TIV, or non-influenza control vaccine, in an efficacy trial conducted 2 years earlier. 197 healthy children aged 30–96 months were randomized to receive vaccination with aTIV or TIV in 2010. To evaluate responses to the first follow-up seasonal vaccination after priming we excluded children who received influenza vaccine(s) in the 2009 pandemic year leaving 40 children vaccinated with aTIV, 26 children with TIV and 10 children with aTIV after a control vaccine in the parent study. Hemagglutination inhibiting antibodies were assayed on Days 1, 22 and 181. aTIV vaccination produced 6.9 to 8.0-fold higher antibody responses than the reference TIV-TIV regimen against A/H3N2 and B strains, which remained higher 6 months following vaccination. The response to the B/Victoria lineage antigen in the second year's vaccine (the first vaccine contained a B/Yamagata lineage antigen) demonstrated that aTIV primed for an adequate response after a single dose on Day 22 (GMTs 160, 95 to antigens in the 2 lineages, respectively), whereas TIV did not (GMTs 38, 20). Vaccination with aTIV produced slightly higher but acceptable local and systemic reactogenicity compared to TIV-TIV and TIV-aTIV mixed regimens. Within the limitations of a small study, the strong immune responses support the use of aTIV for vaccination in young children. PMID:26091244

  11. EVALUATION OF OIL BASED AVIAN INFLUENZA VACCINE (H5NI PREPARED WITH DIFFERENT CONCENTRATIONS OF ADJUVANT

    Directory of Open Access Journals (Sweden)

    M. IQBAL, M. NISAR, ANWARUL-HAQ, S. NOOR AND Z. J. GILL

    2008-12-01

    Full Text Available Bird flu vaccine from H5N1 strain of avian influenza virus was prepared with two concentrations of adjuvant (Montanide ISA 70MVG. Two vaccines (I and II were prepared containing 50 and 60% Montanide, respectively. Immune response of both the vaccines as single, as well as booster, dose was evaluated in layer birds through haemagglutination inhibition test. Single dose of both vaccines showed poor immune response, while booster dose gave better response with both the vaccines. However, the vaccine prepared with 60% Montanide provided better immune response compared with the vaccine containing 50% montanide.

  12. Contamination of DNase Preparations Confounds Analysis of the Role of DNA in Alum-Adjuvanted Vaccines

    OpenAIRE

    Noges, Laura E.; White, Janice; Cambier, John C.; Kappler, John W.; Marrack, Philippa

    2016-01-01

    Aluminum salt (alum) adjuvants have been used for many years as adjuvants for human vaccines because they are safe and effective. Despite its widespread use, the means by which alum acts as an adjuvant remains poorly understood. Recently, it was shown that injected alum is rapidly coated with host chromatin within mice. Experiments suggested that the host DNA in the coating chromatin contributed to alum’s adjuvant activity. Some of the experiments used commercially purchased DNase and showed ...

  13. Concurrent Boost with Adjuvant Breast Hypofractionated Radiotherapy and Toxicity Assessment

    Directory of Open Access Journals (Sweden)

    Mona M. Sayed

    2015-01-01

    Full Text Available Background: The use of shorter radiotherapy schedules has an economic and logistic advantage for radiotherapy departments, as well as a high degree of patient convenience. The aim of this study is to assess the acute and short-term late toxicities of a hypofractionated radiotherapy schedule with a concomitant boost. Methods: We enrolled 57 eligible patients as group A. These patients received 42.5 Gy in 16 fractions of 2.66 Gy each to the whole breast over 3.2 weeks. A concomitant electron boost of 12 Gy in 16 fractions was also administered which gave an additional 0.75 Gy daily to the lumpectomy area for a total radiation dose of 54.5 Gy. Toxicity was recorded at three weeks and at three months for this group as well as for a control group (group B. The control group comprised 76 eligible patients treated conventionally with 50 Gy to the whole breast over five weeks followed by a sequential electron boost of 12 Gy in 2 Gy per fraction. Results: There were no statistically significant differences observed in the incidence of acute skin toxicity, breast pain, and edema recorded at three weeks or pigmentation and fibrosis recorded at three months between the two groups (P0.05. Conclusion: The results of this study suggest there are no increased acute and shortterm late toxicities affiliated with the hypofractionated schedule plus a concomitant boost as prescribed compared to the conventional fractionation of adjuvant breast radiotherapy. Large randomized trials and long-term follow-up are needed to confirm these favorable findings.

  14. Sleep aid use during and following breast cancer adjuvant chemotherapy.

    Science.gov (United States)

    Moore, Tiffany A; Berger, Ann M; Dizona, Paul

    2011-03-01

    Knowledge of sleep aid use is limited despite the high prevalence of insomnia among women before, during, and following breast cancer adjuvant chemotherapy treatments (CTX). This study's purpose was to (1) determine the frequency and characteristics of participants taking sleep aid(s); (2) identify the frequency and percentage of sleep aid use by category (prescription sedative/hypnotics, prescription anti-depressants, prescription analgesics, prescription anti-emetics, over-the-counter (OTC) analgesics, OTC cold/flu/sinus, OTC sleep, alcohol, and herbal supplements); and (3) compare sleep aid use by category in the experimental and control groups within a randomized-controlled clinical trial (RCT). Longitudinal, descriptive, secondary RCT data analysis of women (n=219) receiving out-patient CTX, and at 30, 60, and 90 days following the last CTX and 1 year following CTX1. Participants recorded daily sleep aid use on a Sleep Diary. Analyses included descriptives, chi-square, and RM-ANOVA. Approximately 20% of participants took at least one sleep aid before CTX1; usage decreased over time (12-18%); a second sleep aid was used infrequently. Prescription sedative/hypnotics (46%) and OTC analgesics (24%) were used most frequently. OTC sleep aids were most commonly used as a second aid. Prescription sedative/hypnotics [F(7,211)=4.26, p=0.00] and OTC analgesics [F(7,211)=2.38, p=0.023] use decreased significantly over time. Results reflect the natural course of CTX, recovery, and healing. Comprehensive screening for sleep-wake disturbances and sleep aid use may lead to a better understanding of the risks and benefits of pharmacologic and non-pharmacologic interventions, and ultimately lead to selection of the safest and most effective treatment. Copyright © 2010 John Wiley & Sons, Ltd.

  15. Nickel acts as an adjuvant during cobalt sensitization.

    Science.gov (United States)

    Bonefeld, Charlotte Menné; Nielsen, Morten Milek; Vennegaard, Marie T; Johansen, Jeanne Duus; Geisler, Carsten; Thyssen, Jacob P

    2015-03-01

    Metal allergy is the most frequent form of contact allergy with nickel and cobalt being the main culprits. Typically, exposure comes from metal-alloys where nickel and cobalt co-exist. Importantly, very little is known about how co-exposure to nickel and cobalt affects the immune system. We investigated these effects by using a recently developed mouse model. Mice were epicutaneously sensitized with i) nickel alone, ii) nickel in the presence of cobalt, iii) cobalt alone, or iv) cobalt in the presence of nickel, and then followed by challenge with either nickel or cobalt alone. We found that sensitization with nickel alone induced more local inflammation than cobalt alone as measured by increased ear-swelling. Furthermore, the presence of nickel during sensitization to cobalt led to a stronger challenge response to cobalt as seen by increased ear-swelling and increased B and T cell responses in the draining lymph nodes compared to mice sensitized with cobalt alone. In contrast, the presence of cobalt during nickel sensitization only induced an increased CD8(+) T cell proliferation during challenge to nickel. Thus, the presence of nickel during cobalt sensitization potentiated the challenge response against cobalt more than the presence of cobalt during sensitization to nickel affected the challenge response against nickel. Taken together, our study demonstrates that sensitization with a mixture of nickel and cobalt leads to an increased immune response to both nickel and cobalt, especially to cobalt, and furthermore that the adjuvant effect appears to correlate with the inflammatory properties of the allergen. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Herman, Joseph M., E-mail: jherma15@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Wood, Laura D. [Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Blackford, Amanda L. [Department of Oncology Biostatistics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Ellsworth, Susannah [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Hidalgo, Manuel [Centro Nacional de Investigaciones Oncologicas, Madrid (Spain); Donehower, Ross C. [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Schulick, Richard D.; Edil, Barish H. [Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado (United States); Choti, Michael A. [Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Hruban, Ralph H. [Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); and others

    2013-07-15

    Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m{sup 2} twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m{sup 2} on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

  17. Antigen sparing and enhanced protection using a novel rOv-ASP-1 adjuvant in aqueous formulation with influenza vaccines.

    Science.gov (United States)

    Jiang, Jiu; Fisher, Erin M; Hensley, Scott E; Lustigman, Sara; Murasko, Donna M; Shen, Hao

    2014-05-13

    Influenza is one of the most common infectious diseases endangering the health of humans, especially young children and the elderly. Although vaccination is the most effective means of protection against influenza, frequent mutations in viral surface antigens, low protective efficacy of the influenza vaccine in the elderly, slow production process and the potential of vaccine supply shortage during a pandemic are significant limitations of current vaccines. Adjuvants have been used to enhance the efficacy of a variety of vaccines; however, no adjuvant is included in current influenza vaccines approved in the United States. In this study, we found that a novel adjuvant, rOv-ASP-1, co-administrated with inactivated influenza vaccine using an aqueous formulation, substantially improved the influenza-specific antibody response and protection against lethal infection in a mouse model. rOv-ASP-1 enhanced the magnitude of the specific antibody response after immunization with low doses of influenza vaccine, allowing antigen-sparring by 10-fold. The rOv-ASP-1 formulated vaccine induced a more rapid response and a stronger Th1-associated antibody response compared to vaccine alone and to the vaccine formulated with the adjuvant alum. Importantly, rOv-ASP-1 significantly enhanced cross-reactive antibody responses and protection against challenge with an antigenically distinct strain. These results demonstrate that rOv-ASP-1 is an effective adjuvant that: (1) accelerates and enhances the specific antibody response induced by influenza vaccine; (2) allows for antigen sparing; and (3) augments a Th1-biased and cross-reactive antibody response that confers protection against an antigenically distinct strain. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. A Meta-Analysis of Cognitive Impairment and Decline Associated with Adjuvant Chemotherapy in Women with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Miyuki eOno

    2015-03-01

    Full Text Available A meta-analysis was performed to quantify the magnitude and nature of the association between adjuvant chemotherapy and performance on a range of cognitive domains among breast cancer patients. A total of 27 studies (14 cross-sectional, 8 both cross-sectional and prospective and 5 prospective were included in the analyses, involving 1562 breast cancer patients who had undergone adjuvant chemotherapy and 2799 controls that included breast cancer patients who did not receive adjuvant chemotherapy. A total of 737 effect sizes (Cohen’s d were calculated for cross-sectional and prospective longitudinal studies separately and classified into eight cognitive domains. The mean effect sizes varied across cross-sectional and prospective longitudinal studies (ranging from –1.12 to 0.62, and –0.29 to 1.12, respectively. Each cognitive domain produced small effect sizes for cross sectional and prospective longitudinal studies (ranging from –0.25 to 0.41. Results from cross-sectional studies indicated a significant association between adjuvant chemotherapy and cognitive impairment that held across studies with varied methodological approaches. For prospective studies, results generally indicated that cognitive functioning improved over time after receiving adjuvant chemotherapy. Greater cognitive impairment was reported in cross-sectional studies comparing chemotherapy groups with healthy control groups. Results suggested that cognitive impairment is present among breast cancer patients irrespective of a history of chemotherapy. Prospective longitudinal research is warranted to examine the degree and persisting nature of cognitive impairment present both before and after chemotherapy, with comparisons made to participants’ cognitive function prior to diagnosis. Accurate understanding of the effects of chemotherapy is essential to enable informed decisions regarding treatment and to improve quality of life among breast cancer patients.

  19. Cell-Based Systems Biology Analysis of Human AS03-Adjuvanted H5N1 Avian Influenza Vaccine Responses: A Phase I Randomized Controlled Trial

    Science.gov (United States)

    Samir, Parimal; Galassie, Allison; Allos, Tara M.; Niu, Xinnan; Gordy, Laura E.; Creech, C. Buddy; Prasad, Nripesh; Jensen, Travis L.; Hill, Heather; Levy, Shawn E.; Joyce, Sebastian; Link, Andrew J.; Edwards, Kathryn M.

    2017-01-01

    Background Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. Objective and Methods We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18–49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination. Results Both vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination. Conclusions Using this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed. Trial Registration ClinicalTrials.gov NCT

  20. Heat shock protein 70 as a predictive marker for platinum-based adjuvant chemotherapy in patients with resected non-small cell lung cancer.

    Science.gov (United States)

    Park, Tai Sun; Kim, Hye-Ryoun; Koh, Jae Soo; Jang, Seung Hun; Hwang, Yong Il; Yoon, Ho Il; Chung, Jin-Haeng; Kim, Cheol Hyeon; Kim, Sung-Soo; Kim, Woo Sung; Jo, Jungmin; Lee, Jae Cheol; Choi, Chang-Min

    2014-11-01

    Although adjuvant platinum-based chemotherapy improves survival in completely resected non-small cell lung cancer (NSCLC), its effect is limited. We evaluated whether the expression of heat shock protein 70 (Hsp70) is associated with clinical outcomes in patients with completely resected NSCLC who were treated with or without adjuvant platinum-based chemotherapy. Patients who underwent curative resection for NSCLC and diagnosed as stage IIA through IIIA were included. Immunohistochemical staining for Hsp70 was performed on surgical specimens and survival rates were compared by Hsp70 expression and adjuvant platinum-based chemotherapy. Of 327 enrolled patients, Hsp70 expression was positive in 220 (67.3%). For patients who did not receive adjuvant chemotherapy, Hsp70 expression did not significantly affect survival. However, for patients who received adjuvant chemotherapy, those with Hsp70-positive tumors had a longer disease-free survival outcome than cases with Hsp70-negative tumors (not reached vs. 27.3 months; P=0.002), although there was no significant difference in overall survival (97.0 vs. 58.9 months, P=0.080). In the adjuvant chemotherapy group, multivariate modeling showed that patients with Hsp70-postitive tumors had a lower risk of recurrence and death after adjusting for age, sex, performance status, pathologic stage, and histological type (disease-free survival: adjusted hazard ratio, 0.537; 95% CI, 0.362-0.796; P=0.002; overall survival: adjusted hazard ratio, 0.663; 95% CI, 0.419-1.051; P=0.080). Hsp70 is a positive predictive factor in completely resected NSCLC with received platinum-based adjuvant chemotherapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Trade-offs Between Efficacy and Cardiac Toxicity of Adjuvant Chemotherapy in Early-Stage Breast Cancer Patients: Do Competing Risks Matter?

    Science.gov (United States)

    Alarid-Escudero, Fernando; Blaes, Anne H; Kuntz, Karen M

    2017-07-01

    Evidence about treatment efficacy and long-term toxicities for adjuvant chemotherapy in patients with early-stage breast cancer is often presented in different formats and studies. This leads to challenges for patients and their physicians to adequately weigh the trade-offs between effectiveness and long-term cardiac toxicity when making decisions about adjuvant chemotherapy. We used a decision-analytic framework to quantify these trade-offs by combining the available evidence into a single, comparable metric. We developed a Markov model to simulate a hypothetical cohort of newly diagnosed breast cancer patients under three scenarios: no treatment, anthracycline (AC)-based adjuvant chemotherapy (more effective but also more cardiotoxic), and non-AC-based adjuvant chemotherapy. We derived the model parameters from medical literature (e.g., clinical trials). Our primary outcome is 10-year mortality, and other metrics such as cause of death; life years (LYs) and quality-adjusted LYs over 10 years were evaluated in sensitivity analysis. For 55-year-old women with a 10-year risk of metastatic recurrence <12.5% no chemotherapy resulted in the preferred strategy. In general, non-AC-based adjuvant chemotherapy resulted in lower 10-year mortality than AC-based chemotherapy. Patients with low risk of metastatic recurrence are better off without adjuvant chemotherapy regardless of the outcome considered (i.e., the risks of cardiac toxicity from chemotherapy outweighed the benefits). Trade-offs between effectiveness and induced cardiac toxicity impact health outcomes. The choice of adjuvant treatment must consider the patient's risk of distant recurrence and the quality of life associated with different health outcomes. © 2017 Wiley Periodicals, Inc.

  2. The real-world cost-effectiveness of adjuvant trastuzumab in HER-2/neu-positive early breast cancer in Taiwan.

    Science.gov (United States)

    Lang, Hui-Chu; Chen, Hsiao-Wei; Chiou, Tzeon-Jye; Chan, Agnes L F

    2016-10-01

    Trastuzumab was considered a cost-effective adjuvant treatment for HER 2-positive early breast cancer. Since 2010, the Taiwanese National Health Insurance (NHI) has started to reimburse for 1-year adjuvant treatment. This study aims to provide an updated cost-effectiveness analysis from the NHI perspective, which explores assumptions about long-term cardiac toxicity and treatment benefit of 1-year adjuvant treatment sequentially after chemotherapy. A Markov model was used to evaluate the cost-effectiveness of 1-year adjuvant trastuzumab for HER-2/neu positive early breast cancer over a 20-year life-time horizon. A probability sensitivity analysis using Monte Carlo simulation was performed to characterize uncertainties in the expected outcomes, which are expressed as an incremental costs effectiveness ratio (ICER, cost/QALY). A willingness-to-pay threshold of 3-times the per capita gross domestic product was adopted according to the WHO definition. The Taiwan per capita gross domestic product in 2015 was US$22,355; thus, a threshold was considered as NT$2,011,950 (US$67 065, 1USD =30 NTD in 2015). The model showed that adjuvant trastuzumab treatment in HER-2/neu positive early breast cancer yielded 1.631 quality-adjusted life-years (QALY) compared with no trastuzumab treatment. The ICER was US $51,863 per QALY gained in the base-case scenario. The Monte Carlo simulation by varying all variables simultaneously demonstrated that the probability of cost-effectiveness at the willingness-to-pay threshold of US$67,065 was 50% for 1-year adjuvant trastuzumab. From this real-world study, 1-year adjuvant trastuzumab treatment is likely to be a cost-effective therapy for patients with HER-2 positive breast cancer at the willingness-to-pay threshold of 3-times GDP per capita in Taiwan.

  3. 75 FR 66766 - NIAID Blue Ribbon Panel Meeting on Adjuvant Discovery and Development

    Science.gov (United States)

    2010-10-29

    ... discovery, development and clinical evaluation of adjuvants for use with preventive vaccines. NIAID has developed a draft Strategic Plan and Research Agenda for Adjuvant Discovery and Development, which... HUMAN SERVICES NIAID Blue Ribbon Panel Meeting on Adjuvant Discovery and Development Notice is...

  4. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines.

    Science.gov (United States)

    Hayashi, Masayuki; Aoshi, Taiki; Haseda, Yasunari; Kobiyama, Kouji; Wijaya, Edward; Nakatsu, Noriyuki; Igarashi, Yoshinobu; Standley, Daron M; Yamada, Hiroshi; Honda-Okubo, Yoshikazu; Hara, Hiromitsu; Saito, Takashi; Takai, Toshiyuki; Coban, Cevayir; Petrovsky, Nikolai; Ishii, Ken J

    2017-02-01

    Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

  5. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

    Directory of Open Access Journals (Sweden)

    Masayuki Hayashi

    2017-02-01

    Full Text Available Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV, a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

  6. A single center experience: post-transplantation adjuvant chemotherapy impacts the prognosis of hepatocellular carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Wu Junyi; Sun Hongcheng; Han Zhongbo; Peng Zhihai

    2014-01-01

    Background The aim of this research was to investigate the impact of post-transplantation adjuvant chemotherapy in the prevention of tumor recurrence and metastasis for hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation.Methods A total of 117 patients with HCC exceeding the Milan criteria who had undergone orthotopic liver transplantation (OLT) from August 2002 to February 2009 were enrolled and retrospectively analyzed.The patients were divided into four groups according to chemotherapy regimens and the impact of different chemotherapy regimens on survival,disease-free survival,and adverse effects were compared.Results One year survival rates for the gemicitabine,conventional chemotherapy,oxaliplatin plus capecitabine and the best supportive care (BSC) group were 87.5%,84.2%,81.6%,and 67.5%.The 3-year survival rates were 48.1%,25.9%,31.6%,and 33.7%,respectively for the four groups.One year disease free survival rates for the four groups were 69.8%,47.4%,53.8%,and 45.7% respectively.And 3-year disease free survival rates were 43.2%,23.7%,23.6%,and 25.1% for the four groups.Stratification analysis showed that the gemcitabine regimen and conventional chemotherapy could significantly improve the survival rate and disease free survival rate for HCC patients who had major vascular invasion and/or microvascular invasion after liver transplantation compared with BSC group.Conclusions For HCC patients beyond Milan criteria,especially who had vascular invasion and/or micorvascular invasion,post-transplantation adjuvant chemotherapy can significantly improve survival.Gemcitabine is a proper regimen for postoperative adjuvant chemotherapy.Conventional chemotherapy can also benefit patients,but the adverse effects are not satisfactory.

  7. Lipopolysaccharide contamination in intradermal DNA vaccination : toxic impurity or adjuvant?

    NARCIS (Netherlands)

    Berg, J.H. van den; Quaak, S.G.L.; Beijnen, J.H.; Hennink, W.E.; Storm, G.; Schumacher, T.N.; Haanen, J.B.A.G.; Nuijen, B.

    2010-01-01

    Purpose: Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. Method: Micewere vaccinated with a model DNA v

  8. Postoperative adjuvant chemotherapy in rectal cancer operated for cure

    DEFF Research Database (Denmark)

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky

    2012-01-01

    in Dukes´ C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive...

  9. Evaluation of adjuvant effects of fucoidan for improving vaccine efficacy.

    Science.gov (United States)

    Kim, Su-Yeon; Joo, Hong-Gu

    2015-01-01

    Fucoidan is a sulfated polysaccharide derived from brown seaweed, including Fucus vesiculosus. This compound is known to have immunostimulatory effects on various types of immune cells including macrophages and dendritic cells. A recent study described the application of fucoidan as a vaccine adjuvant. Vaccination is regarded as the most efficient prophylactic method for preventing harmful or epidemic diseases. To increase vaccine efficacy, effective adjuvants are needed. In the present study, we determined whether fucoidan can function as an adjuvant using vaccine antigens. Flow cytometric analysis revealed that fucoidan increases the expression of the activation markers major histocompatibility complex class II, cluster of differentiation (CD)25, and CD69 in spleen cells. In combination with Bordetella bronchiseptica antigen, fucoidan increased the viability and tumor necrosis factor-α production of spleen cells. Furthermore, fucoidan increased the in vivo production of antigen-specific antibodies in mice inoculated with Mycoplasma hyopneumoniae antigen. Overall, this study has provided valuable information about the use of fucoidan as a vaccine adjuvant.

  10. Teaching adjuvant endocrine breast cancer treatment to medical students

    NARCIS (Netherlands)

    Visser, M. de; Fluit, C.R.M.G.; Timmer-Bonte, J.N.H.; Ottevanger, P.B.; Verhagen, C.A.H.H.V.M.; Klaassen, T.; Laarhoven, H.W.M. van

    2013-01-01

    Background: In undergraduate medical education, students are supposed to acquire knowledge and understanding about the basic principles of adjuvant breast cancer treatment. The best education method in this context is unknown. In this randomised study we assessed the effect of designing a patient ed

  11. Local anesthetis and adjuvants in pediatric regional anesthesia.

    Science.gov (United States)

    Mossetti, Valeria; Vicchio, Noemi; Ivani, Giorgio

    2012-06-01

    The pediatric loco-regional techniques are considered very safe and effective, first of all because they target the therapy directly to the site of surgery, decreasing the risks of intravenous analgesia. The quality of local anesthesia is influenced by structural and biophysical characteristics of local anesthetics drug, dose, site of injection, mixture of local anesthetics and possible addition of a vasoconstrictor or an adjuvant to prolong the analgesic effect. In children, unlike adults, small nerve diameters and short distance between Ranvier nodes permit to use large volumes and low concentrations of local anesthetics. The clinical practice has shown that in pediatric population, effective analgesia is obtained by 1% mepivacaine, 1% lidocaine and 0.25% bupivacaine or better 0.2% ropivacaine, 0.2-0.25% levobupivacaine. In addition, levobupivacaine and ropivacaine have a better profile in terms of safety in comparison to bupivacaine and are the local anesthetics of choice for the daily clinical practice also in children as in adults. Among the adjuvant, clonidine and ketamine showed the best pharmacokinetic and pharmacodynamic profiles of effective and safety, improving and prolonging the action of associated local anesthetics. Therefore, the use of enantiomers, in association with adjuvants as clonidine or ketamine, using the multimodal approach of integrated anesthesia, makes the clinical practice effective and safe in the pediatric operating rooms. This review focuses on the overview of local anesthetics and adjuvants used today in locoregional pediatric anesthesia, with an emphasis on the advantages and disadvantages of each drug.

  12. Lipopolysaccharide contamination in intradermal DNA vaccination : toxic impurity or adjuvant?

    NARCIS (Netherlands)

    Berg, J.H. van den; Quaak, S.G.L.; Beijnen, J.H.; Hennink, W.E.; Storm, G.; Schumacher, T.N.; Haanen, J.B.A.G.; Nuijen, B.

    Purpose: Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. Method: Micewere vaccinated with a model DNA

  13. Effects of 5-fluorouracil adjuvant treatment of colon cancer

    NARCIS (Netherlands)

    Kelder, Wendy; Hospers, Geke A. P.; Plukker, John T. M.

    2006-01-01

    Since the late 1980s and early 1990s, 5-fluorouracil-based chemotherapy has been the standard adjuvant treatment for Stage III colon cancer. After the initial introduction of 5-fluorouracil in standard treatment protocols, several changes have been made based on results of randomized studies on vari

  14. Persistent neurocognitive problems after adjuvant chemotherapy for breast cancer

    NARCIS (Netherlands)

    Kreukels, B.P.C.; van Dam, F.S.A.M.; Ridderinkhof, K.R.; Boogerd, W.; Schagen, S.B.

    2008-01-01

    Background: Neurocognitive problems have been observed in a number of women previously treated with adjuvant chemotherapy for breast cancer. The present study aims to combine the results of neuropsychological and electrophysiological techniques collected in patients with breast cancer treated with c

  15. Adjuvant chemotherapy for the perineural invasion of colorectal cancer.

    Science.gov (United States)

    Suzuki, Toshiaki; Suwa, Katsuhito; Ogawa, Masaichi; Eto, Ken; Kawahara, Hidejiro; Fujita, Tetsuji; Ikegami, Masahiro; Yanaga, Katsuhiko

    2015-11-01

    To evaluate the association of perineural invasion (PNI) with outcomes in patients after colorectal resection of colorectal cancer (CRC) and to assess the effect of PNI on the response to adjuvant chemotherapy. Data were retrospectively reviewed for 178 patients with consecutive stages I-III CRC who underwent curative surgery between January 1999 and December 2004. PNI data were examined, and the overall survival (OS) and disease-free survival rates were analyzed. PNI was detected in 36 of 178 patients (20%) and positively correlated with lymphatic invasion (P = 0.020), venous invasion (P = 0.037), and the incidence of metastasis or recurrence (P = 0.029). Five-year disease-free survival was 46% and 68% (P negative prognostic factor of OS; among PNI-positive patients, median OS with adjuvant chemotherapy was almost twofold higher than that without adjuvant chemotherapy (6 versus 2.8 y; P = 0.017). PNI was a poor predictor of survival among patients with stage III CRC, and adjuvant chemotherapy may attenuate the adverse effects of PNI on survival. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Is adjuvant chemotherapy necessary for patients with microinvasive breast cancer after surgery?

    Institute of Scientific and Technical Information of China (English)

    Hai-Fei Niu; Li-Juan Wei; Jin-Pu Yu; Zhen Lian; Jing Zhao; Zi-Zheng Wu; Jun-Tian Liu

    2016-01-01

    Objective:Survival and treatment of patients with microinvasive breast cancer (MIBC) remain controversial. In this paper, we evaluated whether adjuvant chemotherapy is necessary for patients with MIBC to identify risk factors influencing its prognosis and decide the indication for adjuvant chemotherapy. Methods:In this retrospective study, 108 patients with MIBC were recruited according to seventh edition of the staging manual of the American Joint Committee on Cancer (AJCC). The subjects were divided into chemotherapy and non-chemotherapy groups. We compared the 5-year disease-free survival (DFS) and overall survival (OS) rates between groups. Furthermore, we analyzed the factors related to prognosis for patients with MIBC using univariate and multivariate analyses. We also evaluated the impact of adjuvant chemotherapy on the prognostic factors by subgroup analysis after median follow-up time of 33 months (13-104 months). Results:The 5-year DFS and OS rates for the chemotherapy group were 93.7% and 97.5%, whereas those for the non-chemotherapy group were 89.7% and 100%. Results indicate that 5-year DFS was superior, but OS was inferior, in the former group compared with the latter group. However, no statistical significance was observed in the 5-year DFS (P=0.223) or OS (P=0.530) rate of the two groups. Most relevant poor-prognostic factors were Ki-67 overexpression and negative hormonal receptors. Cumulative survival was 98.2%vs. 86.5% between low Ki-67 (≤20%) and high Ki-67 (>20%). The hazard ratio of patients with high Ki-67 was 16.585 [95% confidence interval (CI), 1.969-139.724;P=0.010]. Meanwhile, ER(-)/PR(-) patients with MIBC had cumulative survival of 79.3% compared with 97.5% for ER(+) or PR(+) patients with MIBC. The hazard ratio for ER(-)/PR(-) patients with MIBC was 19.149 (95% CI, 3.702-99.057;P<0.001). Subgroup analysis showed that chemotherapy could improve the outcomes of ER(-)/PR(-) patients (P=0.014), but not those who overexpress Ki-67 (P=0

  17. Editorial--Avoiding Unethical Helicobacter pylori Clinical Trials: Susceptibility-Based Studies and Probiotics as Adjuvants.

    Science.gov (United States)

    Graham, David Y

    2015-10-01

    As a general rule, any clinical study where the result is already known or when the investigator(s) compares an assigned treatment against another assigned treatment known to be ineffective in the study population (e.g., in a population with known clarithromycin resistance) is unethical. As susceptibility-based therapy will always be superior to empiric therapy in any population with a prevalence of antimicrobial resistance >0%, any trial that randomizes susceptibility-based therapy with empiric therapy would be unethical. The journal Helicobacter welcomes susceptibility or culture-guided studies, studies of new therapies, and studies of adjuvants and probiotics. However, the journal will not accept for review any study we judge to be lacking clinical equipoise or which assign subjects to a treatment known to be ineffective, such as a susceptibility-based clinical trial with an empiric therapy comparator. To assist authors, we provide examples and suggestions regarding trial design for comparative studies, for susceptibility-based studies, and for studies testing adjuvants or probiotics.

  18. Adherence to Needed Adjuvant Therapy Could Decrease Recurrence Rates for Rural Patients With Early Breast Cancer.

    Science.gov (United States)

    Xuan, Qijia; Gao, Kun; Song, Ying; Zhao, Shu; Dong, Lina; Zhang, Zhongbai; Zhang, Qingyuan; Wang, Jingxuan

    2016-12-01

    The purpose of this study was to evaluate the differences in stage upon diagnosis, adherence to adjuvant treatment, and recurrence between rural and urban patients with early breast cancer. This retrospective study included 3640 patients with primary breast cancer recruited from 2000 to 2009. Patients who developed recurrence or metastasis were verified by adequate diagnostic imaging modalities and pathology. The χ(2) test was used to compare groups with respect to variables (recurrence and clinicopathologic features). A multivariable Cox proportional hazard regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for breast cancer recurrence risk. Compared with tumors in urban patients, those in rural patients showed higher histologic grade, larger size, more lymphatic metastasis, and higher Ki-67 index; therapy adherence was strongly associated with recurrence in both. Compared with urban patients, the female rural patients had a higher recurrence rate. However, no significant difference in recurrence rates was observed between urban and rural patients following guideline adherence. The results of our study suggest that the later stage upon diagnosis and nonadherence to treatment contribute toward worse breast cancer outcomes among rural patients with breast cancer. Adherence to needed adjuvant therapy could decrease recurrence rates for rural patients with early breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Adjuvant intraoperative photodynamic therapy (AIOPDT) after photosensitization with mTHPC in a CC531 colon carcinoma model in mice

    Science.gov (United States)

    Winkler, Steffi; Prosst, Ruediger L.; Stern, Josef; Rheinwald, Markus; Haase, Thomas; Herfarth, Christian; Gahlen, Johannes

    2001-01-01

    The effectiveness of PDT as an adjuvant alternative therapy method for diverse malignant tumors has been investigated in numerous studies. The therapeutic benefit and extent of side effects is mainly determined by the applied photoactive substance. The second generation photosensitizer (PS) mTHPC is capable of causing selective tumor cell death in colon carcinoma when combined with laser irradiation of a PS specific wavelength. Our study revealed PDT with mTHPC as an efficient adjuvant intraoperative modality after R1/R2 resection of a subcutaneously implanted colon tumor. There was a significant increase of postoperative recurrence-free survival time using PDT compared to a control group in a colon cancer model in nude mice. The accumulation of the PS determined by point spectrometry showed a high tumor-selectivity in the tumor, tumor bed, and overlying skin compared to muscle tissue as reference parameter.

  20. Bone marrow recuperation by AM3 in breast cancer patients submitted to aggressive adjuvant treatment. A preliminary report.

    Science.gov (United States)

    Millá, A; Sanchiz, F; Sada, G; Villarrubia, V G

    1986-01-01

    The results of a prospective randomized study of 46 patients with breast carcinoma are presented. Twenty six patients were treated with AM3 (biological response modifier) associated with adjuvant radiotherapy and chemotherapy. Bone marrow hypoplasia was observed in 26.9% of the patients treated with AM3 compared with a 65% incidence in the control group (P less than 0.05). All patients showed leukopenia in peripheral blood count; however, the nadir of leukocytes was 4,000 leu/mm3 in the test group, compared with 1,900 leu/mm3 in the control group. None of the patients in the AM3 group showed thrombocytopenia, whereas 55% in the control group did. In none of the AM-3-treated cases was it necessary to modify the therapeutic schedule of adjuvant treatment.

  1. Triple negative breast cancer: adjuvant chemotherapy effect on survival.

    Science.gov (United States)

    Steponaviciene, L; Lachej-Mikeroviene, N; Smailyte, G; Aleknavicius, E; Meskauskas, R; Didziapetriene, J

    2011-01-01

    The purpose of this study was to evaluate the overall survival of patients with triple negative breast cancer and the impact of different adjuvant chemotherapy regimens on survival. The study group consisted of 99 breast cancer patients with immunohistochemically confirmed triple negative breast cancer. The impact of various factors as well as the impact of different chemotherapy regimens on survival was evaluated. The overall survival of breast cancer patients was 97.0% (95% CI 90.9-99.0), 84.9% (95% CI 76.1-90.6) and 66.5% (95% CI 55.5-75.3) 10, 30 and 60 months after diagnosis, respectively. Univariate analysis demonstrated that the following were significant risk factors for breast cancer patients survival: patient's age, stage of disease, tumour size, lymph node status, type of surgery and chemotherapy. Better survival was related to younger patients' age, smaller tumour size, lower stage of disease, no lymph nodes involvement. Survival rates were higher among patients who received adjuvant chemotherapy and underwent quadrantectomy. In the multivariate statistical analysis the significant independent prognostic variables influencing survival were lymph node status and adjuvant chemotherapy. Survival rates of the patients, who received adjuvant anthracycline containing chemotherapy were higher, than those in non-anthracycline containing treatment group, but the difference was not statistically significant. Patients who had lymph node status N2-3 and those who did not receive adjuvant chemotherapy showed worse prognosis and survival than other patients. The impact of chemotherapy type (anthracycline containing or non-anthracycline containing) on patients survival was not statistically significant.

  2. The superiority of conservative resection and adjuvant radiation for craniopharyngiomas.

    Science.gov (United States)

    Schoenfeld, Adam; Pekmezci, Melike; Barnes, Michael J; Tihan, Tarik; Gupta, Nalin; Lamborn, Kathleen R; Banerjee, Anu; Mueller, Sabine; Chang, Susan; Berger, Mitchel S; Haas-Kogan, Daphne

    2012-05-01

    The purpose of this study is to evaluate the roles of resection extent and adjuvant radiation in the treatment of craniopharyngiomas. We reviewed the records of 122 patients ages 11-52 years who received primary treatment for craniopharyngioma between 1980 and 2009 at the University of California, San Francisco (UCSF). Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints were development of panhypopituitarism, diabetes insipidus (DI), and visual field defects. Of 122 patients, 30 (24%) were treated with gross total resection (GTR) without radiation therapy (RT), 3 (3%) with GTR + RT, 41 (33.6%) with subtotal resection (STR) without RT, and 48 (39.3%) with STR + RT. Median age at diagnosis was 30 years, with 46 patients 18 years or younger. Median follow-up for all patients was 56.4 months (interquartile range 18.9-144.2 months) and 47 months (interquartile range 12.3-121.8 months) for the 60 patients without progression. Fifty six patients progressed, 10 have died, 6 without progression. Median PFS was 61.1 months for all patients. PFS rate at 2 years was 61.5% (95% CI: 52.1-70.9). OS rate at 10 years was 91.1% (95% CI 84.3-97.9). There was no significant difference in PFS and OS between patients treated with GTR vs. STR + XRT (PFS; p = 0.544, OS; p = 0.735), but STR alone resulted in significantly shortened PFS compared to STR + RT or GTR (p < 0.001 for both). STR was associated with significantly shortened OS compared to STR + RT (p = 0.050) and trended to shorter OS compared to GTR (p = 0.066). GTR was associated with significantly greater risk of developing DI (56.3 vs. 13.3% with STR + XRT, p < 0.001) and panhypopituitarism (54.8 vs. 26.7% with STR + XRT, p = 0.014). In conclusion, for patients with craniopharyngioma, STR + RT may provide superior clinical outcome, achieving better disease control than STR and limiting side effects associated with aggressive surgical resection.

  3. Cooperative intracellular interactions between MyD88 and TRIF are required for CD4 T cell TH1 polarization with a synthetic TLR4 agonist adjuvant

    Science.gov (United States)

    Orr, Mark T.; Duthie, Malcolm S.; Windish, Hillarie Plessner; Lucas, Elyse A.; Guderian, Jeff; Hudson, Thomas E.; Shaverdian, Narek; O’Donnell, Joanne; Desbien, Anthony L.; Reed, Steven G.; Coler, Rhea N.

    2013-01-01

    Summary GLA-SE is a synthetic adjuvant agonist of TLR4 that promotes potent poly-functional TH1 responses. Different TLR4 agonists may preferentially signal via MyD88 or TRIF to exert adjuvant effects. However the contribution of MyD88 and TRIF signaling to the induction of polyclonal TH1 responses by TLR4 agonist adjuvants has not been studied in vivo. To determine whether GLA-SE preferentially signals through MyD88 or TRIF, we evaluated the immune responses against a candidate tuberculosis vaccine antigen following immunization of mice lacking either signaling adapter compared to intact mice. We find that both MyD88 and TRIF are necessary for GLA-SE to induce a poly-functional TH1 immune response characterized by CD4 T cells producing IFN-γ, TNF and IL-2, as well as IgG2c class switching, when paired with the tuberculosis vaccine antigen ID93. Accordingly, the protective efficacy of ID93/GLA-SE immunization against aerosolized Mycobacterium tuberculosis was lost when either signaling molecule was ablated. We demonstrate that MyD88 and TRIF must be expressed in the same cell for the in vivo TH1-skewing adjuvant activity indicating that these two signaling pathways cooperate on an intracellular level. Thus engagement of both the MyD88 and TRIF signaling pathways are essential for the effective adjuvant activity of this TLR4 agonist. PMID:23716300

  4. Impact of adjuvants on CD4(+) T cell and B cell responses to a protein antigen vaccine: Results from a phase II, randomized, multicenter trial.

    Science.gov (United States)

    Leroux-Roels, Geert; Marchant, Arnaud; Levy, Jack; Van Damme, Pierre; Schwarz, Tino F; Horsmans, Yves; Jilg, Wolfgang; Kremsner, Peter G; Haelterman, Edwige; Clément, Frédéric; Gabor, Julian J; Esen, Meral; Hens, Annick; Carletti, Isabelle; Fissette, Laurence; Tavares Da Silva, Fernanda; Burny, Wivine; Janssens, Michel; Moris, Philippe; Didierlaurent, Arnaud M; Van Der Most, Robbert; Garçon, Nathalie; Van Belle, Pascale; Van Mechelen, Marcelle

    2016-08-01

    Immunogenicity and safety of different adjuvants combined with a model antigen (HBsAg) were compared. Healthy HBV-naïve adults were randomized to receive HBs adjuvanted with alum or Adjuvant Systems AS01B, AS01E, AS03A or AS04 at Days 0 and 30. Different frequencies of HBs-specific CD4+ T cells 14days post dose 2 but similar polyfunctionality profiles were induced by the different adjuvants with frequencies significantly higher in the AS01B and AS01E groups than in the other groups. Antibody concentrations 30days post-dose 2 were significantly higher in AS01B, AS01E and AS03A than in other groups. Limited correlations were observed between HBs-specific CD4+ T cell and antibody responses. Injection site pain was the most common solicited local symptom and was more frequent in AS groups than in alum group. Different adjuvants formulated with the same antigen induced different adaptive immune responses and reactogenicity patterns in healthy naïve adults. The results summary for this study (GSK study number 112115 - NCT# NCT00805389) is available on the GSK Clinical Study Register and can be accessed at www.gsk-clinicalstudyregister.com.

  5. Localized Gastric or Gastroesophageal Cancer – Chemoradiation Is a Pertinent Component of Adjuvant Treatment for Patients at High Risk of Relapse

    Science.gov (United States)

    Callister, Matthew D.; Jaroszewski, Dawn E.; Ross, Helen J.; Borad, Mitesh J.; Gray, Richard J.; Lanza, Louis A.; Harold, Kristi L.; Pockaj, Barbara A.; Trastek, Victor F.

    2009-01-01

    The standard of care for resectable gastric or gastroesophageal (GE) junction cancer for patients who can tolerate a surgical procedure is surgical resection, but surgery alone is not optimal treatment for patients at high risk for relapse. For patients with lower-risk lesions (confined to gastric wall, nodes negative; T1-2N0M0), local-regional relapse risks are low, and adjuvant radiotherapy is usually not recommended, except in select instances. Since both local-regional and systemic relapses are common after resection of high-risk gastric or GE junction cancers (beyond wall, nodes positive, or both; T3-4N0, TanyN+), adjuvant treatment is indicated for these patients. The results of phase III trials that demonstrate a survival benefit for adjuvant preoperative radiotherapy, postoperative chemoradiation, or preoperative chemoradiation vs. surgery alone will be presented and compared with the results of adjuvant perioperative chemotherapy. Results of Surveillance, Epidemiology, and End Results (SEER) analyses and meta-analyses that support the role of adjuvant radiotherapy or chemoradiation will be summarized. PMID:19461920

  6. Combining viral vectored and protein-in-adjuvant vaccines against the blood-stage malaria antigen AMA1: report on a phase 1a clinical trial.

    Science.gov (United States)

    Hodgson, Susanne H; Choudhary, Prateek; Elias, Sean C; Milne, Kathryn H; Rampling, Thomas W; Biswas, Sumi; Poulton, Ian D; Miura, Kazutoyo; Douglas, Alexander D; Alanine, Daniel Gw; Illingworth, Joseph J; de Cassan, Simone C; Zhu, Daming; Nicosia, Alfredo; Long, Carole A; Moyle, Sarah; Berrie, Eleanor; Lawrie, Alison M; Wu, Yimin; Ellis, Ruth D; Hill, Adrian V S; Draper, Simon J

    2014-12-01

    The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines--chimpanzee adenovirus ChAd63 and the orthopoxvirus MVA. A variety of promising "mixed-modality" regimens were tested. All volunteers were primed with ChAd63, and then subsequently boosted with MVA and/or protein-in-adjuvant using either an 8- or 16-week prime-boost interval. We report on the safety of these regimens, as well as the T cell, B cell, and serum antibody responses. Notably, IgG antibody responses primed by ChAd63 were comparably boosted by AMA1 protein vaccine, irrespective of whether CPG 7909 was included in the Alhydrogel adjuvant. The ability to improve the potency of a relatively weak aluminium-based adjuvant in humans, by previously priming with an adenoviral vaccine vector encoding the same antigen, thus offers a novel vaccination strategy for difficult or neglected disease targets when access to more potent adjuvants is not possible.

  7. Alternative inactivated poliovirus vaccines adjuvanted with Quillaja brasiliensis or Quil-a saponins are equally effective in inducing specific immune responses.

    Directory of Open Access Journals (Sweden)

    Fernanda de Costa

    Full Text Available Inactivated polio vaccines (IPV have an important role at the final stages of poliomyelitis eradication programs, reducing the risks associated with the use of attenuated polio vaccine (OPV. An affordable option to enhance vaccine immunogenicity and reduce costs of IPV may be the use of an effective and renewable adjuvant. In the present study, the adjuvant activity of aqueous extract (AE and saponin fraction QB-90 from Quillaja brasiliensis using poliovirus antigen as model were analyzed and compared to a preparation adjuvanted with Quil-A, a well-known saponin-based commercial adjuvant. Experimental vaccines were prepared with viral antigen plus saline (control, Quil-A (50 µg, AE (400 µg or QB-90 (50 µg. Sera from inoculated mice were collected at days 0, 28, 42 and 56 post-inoculation of the first dose of vaccine. Serum levels of specific IgG, IgG1 and IgG2a were significantly enhanced by AE, QB-90 and Quil-A compared to control group on day 56. The magnitude of enhancement was statistically equivalent for QB-90 and Quil-A. The cellular response was evaluated through DTH and analysis of IFN-γ and IL-2 mRNA levels using in vitro reestimulated splenocytes. Results indicated that AE and QB-90 were capable of stimulating the generation of Th1 cells against the administered antigen to the same extent as Quil-A. Mucosal immune response was enhanced by the vaccine adjuvanted with QB-90 as demonstrated by increases of specific IgA titers in bile, feces and vaginal washings, yielding comparable or higher titers than Quil-A. The results obtained indicate that saponins from Q. brasiliensis are potent adjuvants of specific cellular and humoral immune responses and represent a viable option to Quil-A.

  8. A rabies vaccine adjuvanted with saponins from leaves of the soap tree (Quillaja brasiliensis) induces specific immune responses and protects against lethal challenge.

    Science.gov (United States)

    Yendo, Anna Carolina A; de Costa, Fernanda; Cibulski, Samuel P; Teixeira, Thais F; Colling, Luana C; Mastrogiovanni, Mauricio; Soulé, Silvia; Roehe, Paulo M; Gosmann, Grace; Ferreira, Fernando A; Fett-Neto, Arthur G

    2016-04-29

    Quillaja brasiliensis (Quillajaceae) is a saponin producing species native from southern Brazil and Uruguay. Its saponins are remarkably similar to those of Q. saponaria, which provides most of the saponins used as immunoadjuvants in vaccines. The immunostimulating capacities of aqueous extract (AE) and purified saponin fraction (QB-90) obtained from leaves of Q. brasiliensis were favorably comparable to those of a commercial saponin-based adjuvant preparation (Quil-A) in experimental vaccines against bovine herpesvirus type 1 and 5, poliovirus and bovine viral diarrhea virus in mice model. Herein, the immunogenicity and protection efficacy of rabies vaccines adjuvanted with Q. brasiliensis AE and its saponin fractions were compared with vaccines adjuvanted with either commercial Quil-A or Alum. Mice were vaccinated with one or two doses (on days 0 and 14) of one of the different vaccines and serum levels of total IgG, IgG1 and IgG2a were quantified over time. A challenge experiment with a lethal dose of rabies virus was carried out with the formulations. Viral RNA detection in the brain of mice was performed by qPCR, and RNA copy-numbers were quantified using a standard curve of in vitro transcribed RNA. All Q. brasiliensis saponin-adjuvanted vaccines significantly enhanced levels of specific IgG isotypes when compared with the no adjuvant group (P ≤ 0.05). Overall, one or two doses of saponin-based vaccine were efficient to protect against the lethal rabies exposure. Both AE and saponin fractions from Q. brasiliensis leaves proved potent immunological adjuvants in vaccines against a lethal challenge with a major livestock pathogen, hence confirming their value as competitive or complementary sustainable alternatives to saponins of Q. saponaria.

  9. Dexmedetomidine as an Anesthetic Adjuvant in Cardiac Surgery: a Cohort Study

    Science.gov (United States)

    Brandão, Paulo Gabriel Melo; Lobo, Francisco Ricardo; Ramin, Serginando Laudenir; Sakr, Yasser; Machado, Mauricio Nassau; Lobo, Suzana Margareth

    2016-01-01

    OBJECTIVE: α-2-agonists cause sympathetic inhibition combined with parasympathetic activation and have other properties that could be beneficial during cardiac anesthesia. We evaluated the effects of dexmedetomidine as an anesthetic adjuvant compared to a control group during cardiac surgery. METHODS: We performed a retrospective analysis of prospectively collected data from all adult patients (> 18 years old) undergoing cardiac surgery. Patients were divided into two groups, regarding the use of dexmedetomidine as an adjuvant intraoperatively (DEX group) and a control group who did not receive α-2-agonist (CON group). RESULTS: A total of 1302 patients who underwent cardiac surgery, either coronary artery bypass graft or valve surgery, were included; 796 in the DEX group and 506 in the CON group. Need for reoperation (2% vs. 2.8%, P=0.001), type 1 neurological injury (2% vs. 4.7%, P=0.005) and prolonged hospitalization (3.1% vs. 7.3%, P=0.001) were significantly less frequent in the DEX group than in the CON group. Thirty-day mortality rates were 3.4% in the DEX group and 9.7% in the CON group (P<0.001). Using multivariable Cox regression analysis with in hospital death as the dependent variable, dexmedetomidine was independently associated with a lower risk of 30-day mortality (odds ratio [OR]=0.39, 95% confidence interval [CI]: 0.24-0.65, P≤0.001). The Logistic EuroSCORE (OR=1.05, 95% CI: 1.02-1.10, P=0.004) and age (OR=1.03, 95% CI: 1.01-1.06, P=0.003) were independently associated with a higher risk of 30-day mortality. CONCLUSION: Dexmedetomidine used as an anesthetic adjuvant was associated with better outcomes in patients undergoing coronary artery bypass graft and valve surgery. Randomized prospective controlled trials are warranted to confirm our results. PMID:27737403

  10. Efficacy comparison of adjuvants in PcrV vaccine against Pseudomonas aeruginosa pneumonia.

    Science.gov (United States)

    Hamaoka, Saeko; Naito, Yoshifumi; Katoh, Hideya; Shimizu, Masaru; Kinoshita, Mao; Akiyama, Koichi; Kainuma, Atsushi; Moriyama, Kiyoshi; Ishii, Ken J; Sawa, Teiji

    2017-02-01

    Vaccination against the type III secretion system of P. aeruginosa is a potential prophylactic strategy for reducing the incidence and improving the poor prognosis of P. aeruginosa pneumonia. In this study, the efficacies of three different adjuvants, Freund's adjuvant (FA), aluminum hydroxide (alum) and CpG oligodeoxynucleotide (ODN), were examined from the viewpoint of inducing PcrV-specific immunity against virulent P. aeruginosa. Mice that had been immunized intraperitoneally with recombinant PcrV formulated with one of the above adjuvants were challenged intratracheally with a lethal dose of P. aeruginosa. The PcrV-FA immunized group attained a survival rate of 91%, whereas the survival rates of the PcrV-alum and PcrV-CpG groups were 73% and 64%, respectively. In terms of hypothermia recovery after bacterial instillation, PcrV-alum was the most protective, followed by PcrV-FA and PcrV-CpG. The lung edema index was lower in the PcrV-CpG vaccination group than in the other groups. PcrV-alum immunization was associated with the greatest decrease in myeloperoxidase in infected lungs, and also decreased the number of lung bacteria to a similar number as in the PcrV-FA group. There was less neutrophil recruitment in the lungs of mice vaccinated with PcrV-alum or PcrV-CpG than in those of mice vaccinated with PcrV-FA or PcrV alone. Overall, in terms of mouse survival the PcrV-CpG vaccine, which could be a relatively safe next-generation vaccine, showed a comparable effect to the PcrV-alum vaccine.

  11. Adjuvant effects of aluminium hydroxide-adsorbed allergens and allergoids - differences in vivo and in vitro.

    Science.gov (United States)

    Heydenreich, B; Bellinghausen, I; Lund, L; Henmar, H; Lund, G; Adler Würtzen, P; Saloga, J

    2014-06-01

    Allergen-specific immunotherapy (SIT) is a clinically effective therapy for immunoglobulin (Ig)E-mediated allergic diseases. To reduce the risk of IgE-mediated side effects, chemically modified allergoids have been introduced. Furthermore, adsorbance of allergens to aluminium hydroxide (alum) is widely used to enhance the immune response. The mechanisms behind the adjuvant effect of alum are still not completely understood. In the present study we analysed the effects of alum-adsorbed allergens and allergoids on their immunogenicity in vitro and in vivo and their ability to activate basophils of allergic donors. Human monocyte derived dendritic cells (DC) were incubated with native Phleum pratense or Betula verrucosa allergen extract or formaldehyde- or glutaraldehyde-modified allergoids, adsorbed or unadsorbed to alum. After maturation, DC were co-cultivated with autologous CD4(+) T cells. Allergenicity was tested by leukotriene and histamine release of human basophils. Finally, in-vivo immunogenicity was analysed by IgG production of immunized mice. T cell proliferation as well as interleukin (IL)-4, IL-13, IL-10 and interferon (IFN)-γ production were strongly decreased using glutaraldehyde-modified allergoids, but did not differ between alum-adsorbed allergens or allergoids and the corresponding unadsorbed preparations. Glutaraldehyde modification also led to a decreased leukotriene and histamine release compared to native allergens, being further decreased by adsorption to alum. In vivo, immunogenicity was reduced for allergoids which could be partly restored by adsorption to alum. Our results suggest that adsorption of native allergens or modified allergoids to alum had no consistent adjuvant effect but led to a reduced allergenicity in vitro, while we observed an adjuvant effect regarding IgG production in vivo.

  12. Nanoparticles as a vaccine adjuvant of anti-idiotypic antibody against schistosomiasis

    Institute of Scientific and Technical Information of China (English)

    冯振卿; 钟石根; 李玉华; 李芸茜; 仇镇宁; 王祝鸣; 李军; 董莉; 管晓虹

    2004-01-01

    Background The development of new adjuvants for human use has been the focus of attention. This study's aim is to explore the possibility of using nanoparticle Ca nanoparticles (CA) as a vaccine adjuvant of anti-idiotypic antibody NP30 against schistosomiasis and its protective mechanisms. Methods Nanoparticle CA-NP30 conjugate (CA-NP30) was fabricated. BALB/c mice were immunized actively with CA-NP30 to evaluate its effects of protective immunity on mice. The serum levels of specific IgG, IgG1 and IgG2a antibodies against NP30 and the concentrations of IFN-γ and IL-4 in supernatant of splenocytes were determined via ELISA. Results Nanoparticle CA could enhance significantly the protective immunity of NP30 against infection of Schistosoma japonicum and the worm reduction rose from 36.0% (NP30 alone) to 52.6%. The serum levels of specific IgG, IgG1 and IgG2a antibodies against NP30 increased remarkably, as compared with those of the group immunized with NP30 alone. The concentration of IFN-γ in supernatant of splenocyte was drastically elevated [the groups immunized with CA-NP30 and NP30 alone were (493.80±400.74) pg/ml and (39.03±39.58) pg/ml, respectively], but the concentration of IL-4 showed no significant difference from that of NP30 alone [(27.94±9.84) pg/ml vs (27.28±14.44) pg/ml]. Conclusions Nanoparticle CA could act as a vaccine adjuvant of anti-idiotypic antibody NP30 against schistosomiasis. The mechanism could be that CA-NP30 enhances humoral and cellular immune responses in mice.

  13. Does adjuvant radiation therapy benefit women with small mammography-detected breast cancers?

    Science.gov (United States)

    Jerzak, K.; Dudalski, N.; Pritchard, K.; Sun, P.; Narod, S.A.

    2017-01-01

    Background Women with small nonpalpable breast tumours have an excellent prognosis. The benefit of radiotherapy in this group of low-risk women is unknown. Methods A cohort of 1595 women with stages i–iii invasive breast cancer treated with breast-conserving surgery were followed for local recurrence. Using t-tests, baseline demographic data and tumour characteristics were compared for the women who had palpable (n = 1023) and mammography-detected (n = 572) breast cancers. The 15-year actuarial risk of local recurrence was estimated using a Kaplan–Meier method, stratified for adjuvant radiation therapy (yes or no), tumour palpability (palpable or not), and tumour size (≤1 cm or >1 cm). Hazard ratios (hrs) and 95% confidence intervals (95% cis) were calculated using a multivariate Cox regression model. Results were considered statistically significant if 2-tailed p values were less than 0.05. Results Among women with a nonpalpable tumour, the 15-year actuarial rates of local recurrence were, respectively, 13.9% and 18.3% for those treated and not treated with adjuvant radiation therapy (hr: 0.65; 95%ci: 0.40 to 1.06; p = 0.08). Among women with small nonpalpable breast cancers (≤1.0 cm), the rates were 14.6% and 13.4% respectively (p = 0.67). The absolute reduction in 15-year local recurrence was 11.0% for women with palpable tumours. Conclusions Our results suggest that women with small (<1 cm) screen-detected nonpalpable breast cancers likely derive little benefit from adjuvant radiotherapy; however, an adequately powered randomized trial would be required to make definitive conclusions. PMID:28270722

  14. Enhancement of HIV-1 DNA vaccine immunogenicity by BCG-PSN, a novel adjuvant.

    Science.gov (United States)

    Sun, Jing; Hou, Jue; Li, Dingfeng; Liu, Yong; Hu, Ningzhu; Hao, Yanling; Fu, Jingjing; Hu, Yunzhang; Shao, Yiming

    2013-01-07

    Although the importance of DNA vaccines, especially as a priming immunization has been well established in numerous HIV vaccine studies, the immunogenictiy of DNA vaccines is generally moderate. Novel adjuvant is in urgent need for improving the immunogenicity of DNA vaccine. Polysaccharide and nucleic acid fraction extracted by hot phenol method from Mycobacterium bovis bacillus Calmette-Guérin, known as BCG-PSN, is a widely used immunomodulatory product in China clinical practice. In this study, we evaluated whether the BCG-PSN could serve as a novel adjuvant of DNA vaccine to trigger better cellular and humoral immune responses against the HIV-1 Env antigen in Balb/C mouse model. The BCG-PSN was mixed with 10 μg or 100 μg of pDRVI1.0gp145 (HIV-1 CN54 gp145 gene) DNA vaccine and intramuscularly immunized two or three times. We found that BCG-PSN could significantly improve the immunogenicity of DNA vaccine when co-administered with DNA vaccine. Further, at the same vaccination schedule, BCG-PSN co-immunization with 10 μg DNA vaccine could elicit cellular and humoral immune responses which were comparable to that induced by 100 μg DNA vaccine alone. Moreover, our results demonstrate that BCG-PSN can activate TLR signaling pathways and induce Th1-type cytokines secretion. These findings suggest that BCG-PSN can serve as a novel and effective adjuvant for DNA vaccination. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

    Science.gov (United States)

    Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin CS; Peter, Aniekan I; Azu, Onyemaechi O

    2016-01-01

    Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A–D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof. PMID:27818734

  16. Enhanced humoral and Type 1 cellular immune responses with Fluzone adjuvanted with a synthetic TLR4 agonist formulated in an emulsion.

    Science.gov (United States)

    Baldwin, Susan L; Shaverdian, Narek; Goto, Yasuyuki; Duthie, Malcolm S; Raman, Vanitha S; Evers, Tara; Mompoint, Farah; Vedvick, Thomas S; Bertholet, Sylvie; Coler, Rhea N; Reed, Steven G

    2009-10-09

    Impairments in anti-influenza T helper 1 (Th1) responses are associated with greater risk of influenza-related mortality in the elderly. Addition of adjuvants to existing influenza vaccines could improve immune responses in the elderly. In this study, the activity of three adjuvants, an oil-in-water emulsion and a synthetic lipid A adjuvant formulated with or without the emulsion, is compared. Our results show that Fluzone combined with lipid A plus an emulsion effectively leads to greater vaccine-specific IgG2a and IgG titers, enhances hemagglutination-inhibition titers and induces Type 1 cytokine responses (IFN-gamma and IL-2) to each of the Fluzone components.

  17. Tumor tissue levels of tissue inhibitor of metalloproteinases-I (TIMP-I) and outcome following adjuvant chemotherapy in premenopausal lymph node-positive breast cancer patients

    DEFF Research Database (Denmark)

    Schrohl, Anne-Sofie; Look, Maxime P.; Gelder, Marion E. Meijer-van

    2009-01-01

    an association between shorter survival after treatment in TIMP-1 high patients compared with TIMP-1 low patients, especially in patients receiving anthracycline-based therapy. This suggests that high tumor tissue levels of TIMP-1 might be associated with reduced benefit from classical adjuvant chemotherapy. Our......BACKGROUND: We have previously demonstrated that high tumor tissue levels of TIMP-1 are associated with no or limited clinical benefit from chemotherapy with CMF and anthracyclines in metastatic breast cancer patients. Here, we extend our investigations to the adjuvant setting studying outcome...... after adjuvant chemotherapy in premenopausal lymph node-positive patients. We hypothesize that TIMP-1 high tumors are less sensitive to chemotherapy and accordingly that high tumor tissue levels are associated with shorter survival. METHODS: From our original retrospectively collected tumor samples we...

  18. Comparison of doxorubicin-cyclophosphamide with doxorubicin-dacarbazine for the adjuvant treatment of canine hemangiosarcoma.

    Science.gov (United States)

    Finotello, R; Stefanello, D; Zini, E; Marconato, L

    2017-03-01

    Canine hemangiosarcoma (HSA) is a neoplasm of vascular endothelial origin that has an aggressive biological behaviour, with less than 10% of dogs alive at 12-months postdiagnosis. Treatment of choice consists of surgery followed by adjuvant doxorubicin-based chemotherapy. We prospectively compared adjuvant doxorubicin and dacarbazine (ADTIC) to a traditional doxorubicin and cyclophosphamide (AC) treatment, aiming at determining safety and assessing whether this regimen prolongs survival and time to metastasis (TTM). Twenty-seven dogs were enrolled; following staging work-up, 18 were treated with AC and 9 with ADTIC. Median TTM and survival time were longer for dogs treated with ADTIC compared with those receiving AC (>550 versus 112 days, P = 0.021 and >550 versus 142 days, P = 0.011, respectively). Both protocols were well tolerated, without need for dose reduction or increased interval between treatments. A protocol consisting of combined doxorubicin and dacarbazine is safe in dogs with HSA and prolongs TTM and survival time. © 2015 John Wiley & Sons Ltd.

  19. Antiarthritic activity of a polyherbal formulation against Freund's complete adjuvant induced arthritis in Female Wistar rats

    Science.gov (United States)

    Petchi, R. Ramesh; Parasuraman, S.; Vijaya, C.; Gopala Krishna, S. V.; Kumar, M. Kiran

    2015-01-01

    Objectives: To formulate a polyherbal formulation and evaluate its antiarthritic activity against Freund's complete adjuvant induced arthritis in Female Wistar rats. Materials and Methods: Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known plants available throughout India and they are commonly used for the treatment of various diseases including arthritis. The polyherbal formulation was formulated using the ethanol extracts of the stem bark of G. pentaphylla, whole plant of T. procumbens, and leaves of M. indica. The polyherbal formulation contains the ethanol extracts of G. pentaphylla, T. procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished product was evaluated as per the World Health Organization's guidelines for the quality control of herbal materials. Arthritis was induced in female Wistar rats using Freund's complete adjuvant (FCA), and the antiarthritic effect of polyherbal formulation was studied at doses of 250 and 500 mg/kg. The effects were compared with those of indomethacin (10 mg/kg). At the end of the study, blood samples were collected for biochemical and hematological analysis. The radiological examination was carried out before terminating the study. Results: Polyherbal formulation showed significant antiarthritic activity at 250 and 500 mg/kg, respectively, and this effect was comparable with that of indomethacin. The antiarthritic activity of polyherbal formulation is supported by biochemical and hematological analysis. Conclusion: The polyherbal formulation showed signinicant antiarthritic activity against FCA-induced arthritis in female Wistar rats. PMID:26229343

  20. Recombinant Moraxella bovoculi cytotoxin-ISCOM matrix adjuvanted vaccine to prevent naturally occurring infectious bovine keratoconjunctivitis.

    Science.gov (United States)

    Angelos, John A; Lane, V Michael; Ball, Louise M; Hess, John F

    2010-03-01

    A randomized, blinded, controlled field trial was conducted during summer 2006 in a northern California, USA, herd of beef cattle to evaluate the efficacy of a recombinant Moraxella bovoculi cytotoxin subunit vaccine to prevent naturally occurring infectious bovine keratoconjunctivitis (IBK; pinkeye). A convenience sample comprised of 127 steers were administered a subcutaneous dose of either adjuvant alone (ISCOM matrices; control group) or recombinant M. bovoculi cytotoxin carboxy terminus adjuvanted with ISCOM matrices (MbvA group) and were boostered 21 days later. The steers were examined once weekly for 15 weeks for evidence of IBK. No significant difference in the cumulative proportion of corneal ulcerations was detected between groups. Compared to the control calves, the MbvA vaccinates had significantly higher increases in serum neutralizing titers to M. bovoculi hemolysin between week 0 and week 6. The prevalence of M. bovis isolations was higher from ulcerated eyes of calves vaccinated with MbvA as compared to control calves. Vaccination of calves against the carboxy terminus of M. bovoculi RTX toxin resulted in significant increases in serum hemolysin neutralizing titers and may modulate organism type cultured from ulcerated eyes of calves in herds where both M. bovis and M. bovoculi exist. Use of M. bovoculi antigens alone in vaccines to prevent IBK may not be beneficial in herds where IBK is associated with both M. bovoculi and M. bovis.

  1. Combination of adjuvant chemotherapy and radiotherapy is associated with improved survival at early stage type II endometrial cancer and carcinosarcoma.

    Science.gov (United States)

    Sozen, Hamdullah; Çiftçi, Rumeysa; Vatansever, Dogan; Topuz, Samet; Iyibozkurt, Ahmet Cem; Bozbey, Hamza Ugur; Yaşa, Cenk; Çali, Halime; Yavuz, Ekrem; Kucucuk, Seden; Aydiner, Adnan; Salihoglu, Yavuz

    2016-04-01

    The aim of this study was to describe the impact of postoperative adjuvant treatment modalities and identify risk factors associated with recurrence and survival rates in women diagnosed with early stage type II endometrial cancer and carcinosarcoma. In this retrospective study, patients diagnosed with early stage (stages I-II) carcinosarcoma and type II endometrial cancer were reviewed. All women underwent comprehensive surgical staging. Postoperative treatment options of chemotherapy (CT), radiotherapy (RT), observation (OBS) and chemotherapy-radiotherapy (CT-RT) combination were compared in terms of recurrence and survival outcome. In CT-RT treatment arm, recurrence rate was found as 12.5% and this result is significantly lower than the other treatment approaches (P = 0.01 CT alone: 33.3%, RT alone: 26.7%, OBS: 62.5%). Three-year disease free survival(DFS) rate and overall survival (OS) rate were statistically higher for the group of women treated with combination of CT-RT (92-95%) compared to the women treated with RT alone (65-72%), treated with CT alone (67-74%) and women who received no adjuvant therapy (38-45%). The multivariate analysis revealed that carcinosarcoma histology was associated with shortened DFS and OS (P = 0.001, P = 0.002). On the other hand, being at stage Ia (P = 0.01, P = 0.04) and receiving adjuvant treatment of CT-RT combination (P = 0.005, P = 0.002) appeared to lead to increased DFS and OS rates. We identified that a combination treatment of chemotherapy and radiotherapy is superior compared to other postoperative adjuvant treatment approaches concerning PFS, OS and recurrence rates in stages I-II of type II endometrial cancers and uterine carcinosarcoma. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  2. Trastuzumab in the adjuvant treatment of HER2-positive early breast cancer patients: a meta-analysis of published randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Wenjin Yin

    Full Text Available BACKGROUND: Adjuvant trastuzumab therapy has yielded conflicting results for overall survival, concerns about central nervous system (CNS metastasis, and questions about optimal schedule. Therefore, we carried out a meta-analysis to assess the benefits of concurrent or sequential trastuzumab with adjuvant chemotherapy for early breast cancer patients with HER2-positive tumors. METHODS: Computerized and manual searches were performed to identify randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in HER2-positive early breast cancer patients. Odds ratios were used to estimate the association between the addition of trastuzumab to adjuvant chemotherapy and various survival outcomes. The fixed-effects or random-effects model was used to combine data. FINDINGS: With six eligible studies identified, this analysis demonstrated that patients with HER2-positive breast cancer derived benefit in disease-free survival, overall survival, locoregional recurrence and distant recurrence (all P<0.001 from the addition of trastuzumab to adjuvant chemotherapy, whereas trastuzumab did worse in CNS recurrence as compared to the control group (P = 0.018. Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001 but bore a higher incidence of CNS recurrence (P = 0.010, while statistical significance failed to be discerned for either overall survival (P = 0.069 or CNS metastasis (P = 0.374 between the sequential and observation arms. CONCLUSION: This analysis verifies the efficacy of trastuzumab in the adjuvant setting. Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation.

  3. Taxane therapy in the adjuvant treatment of breast cancer in Italy: economic evaluation

    Directory of Open Access Journals (Sweden)

    Simona Ravera

    2006-03-01

    Full Text Available Breast cancer (BC is one of the leading cause of death in developed Countries and every year more than a million new cases are diagnosed worldwide. In Italy the prevalence of BC was estimated to be 1,070 per 100,000 at 31 December 1992. Nevertheless, despite the increase in incidence, mortality rate for BC are decreased in the last decades probably due to several factors such as implementation of screening programs, early diagnosis and new adjuvant therapies. Important types of adjuvant chemotherapy include anthracyclines and taxanes and these treatments continue to be evaluated to determine optimal combinations and dosing regimens. The efficacy of paclitaxel and docetaxel in adjuvant setting for the treatment of early BC has been assessed in different trials where the two taxanes showed a significant increase in both Disease Free Survival (DFS and Overall Survival (OS in comparison with nontaxane therapy. In particular results from one of the last studies comparing paclitaxel and docetaxel show equivalent efficacy for both drugs. At the light of the recent findings, the objective of this work is to perform a cost minimization analysis of paclitaxel vs docetaxel in the adjuvant setting for treatment of early BC in Italy. The analysis was conducted from the National Health Service’s point of view, assuming equivalent efficacy in terms of DFS and OS for both taxanes. Costs were evaluated on the basis of therapeutic schemes used in the analyzed trials. Results show that paclitaxel, administered every 3 weeks for 4 cycles after doxorubicin and cyclophosphamide, represents the less costly therapy. This is a conservative costs estimate based on data from literature that does not take into account possible additional costs associated to the treatment of febrile neutropenia (FN as adverse event related to chemotherapy. Since, on the basis of scientific literature data, FN seems to be more related with docetaxel than with paclitaxel administration, it

  4. Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sher, David J., E-mail: dsher@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Thotakura, Vijaya [Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Balboni, Tracy A. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Lorch, Jochen [Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Goguen, Laura A.; Annino, Donald J. [Department of Surgery, Division of Otolaryngology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Tishler, Roy B. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2011-11-15

    Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distribution of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with promising LRC

  5. Evaluation of bone targeting salmon calcitonin analogues in rats developing osteoporosis and adjuvant arthritis.

    Science.gov (United States)

    Bhandari, Krishna H; Asghar, Waheed; Newa, Madhuri; Jamali, Fakhreddin; Doschak, Michael R

    2015-01-01

    showed a trend towards increased BMD and bone volume at 4, 8 and 12 weeks. Significant preservation of bone volume and BMD as evidenced by nonsignificant (Pcalcitonin compounds. Similarly, in case of adjuvant-induced arthritis rats, there was a significant increase (Pcalcitonin-bisphosphonate and calcitonin-PEG-bisphosphonate treated groups at 21 days compared to the baseline values. Improved efficacy in terms of preserving bone volume and BMD in Osteoporosis, and in rats developing adjuvant-induced arthritis, by these analogues suggests their potential as new drug candidates for further evaluation to determine their usefulness in bone diseases characterized by excessive bone resorption.

  6. CAF01 adjuvant increases the protection conferred by a commercially available influenza split vaccine in a ferret model

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Jensen, Trine Hammer; Nielsen, Lars Peter;

    The immunogenicity and efficacy of preventive vaccines against influenza are considered suboptimal and the development of novel influenza vaccination strategies is urgently needed. Commercially available trivalent split vaccines are known to elicit mainly a humoral immune response, whereas...... the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6’-dibehenate, CAF01) was developed, which was proven to enhance both humoral and cell-mediated immune responses of a number of vaccine candidates. In the current study......, we compared the immune response in ferrets vaccinated with a commercial influenza split vaccine with the same vaccine mixed with the CAF01 adjuvant and furthermore used two recently circulating H1N1 viruses for the challenge of the animals. We investigated antibody levels in serum and nasal washes...

  7. Survival in women with ovarian cancer before and after the introduction of adjuvant paclitaxel; a 25-year, single institution review.

    LENUS (Irish Health Repository)

    Shireen, R

    2012-02-01

    Adjuvant chemotherapy regime for ovarian cancer patients remains to be a contentious issue. The aim of this study was to compare the overall and progression-free survival of women with ovarian cancer before and after introduction of paclitaxel in our unit in 1992. A sample of 112 women who received adjuvant therapy following surgery for ovarian cancer was collected, 68 (61%) received platinum+alkylating agent before 1992 and later 44 (39%) received platinum+paclitaxel. Five-year survival was same in both treatment groups when there was no macroscopic disease after surgery (78% versus 70%) and when residual disease was <2 cm (50% versus 40%). Survival was greater in women with residual disease >2 cm in the platinum+paclitaxel group (50% versus 24%), (p = 0.04). However, progression-free survival was similar in both groups irrespective of stage or residual volume of disease. Therefore consideration to selective use of paclitaxel could reduce patient morbidity and costs significantly.

  8. Survival in women with ovarian cancer before and after the introduction of adjuvant paclitaxel; a 25-year, single institution review.

    LENUS (Irish Health Repository)

    Shireen, R

    2012-02-01

    Adjuvant chemotherapy regime for ovarian cancer patients remains to be a contentious issue. The aim of this study was to compare the overall and progression-free survival of women with ovarian cancer before and after introduction of paclitaxel in our unit in 1992. A sample of 112 women who received adjuvant therapy following surgery for ovarian cancer was collected, 68 (61%) received platinum+alkylating agent before 1992 and later 44 (39%) received platinum+paclitaxel. Five-year survival was same in both treatment groups when there was no macroscopic disease after surgery (78% versus 70%) and when residual disease was <2 cm (50% versus 40%). Survival was greater in women with residual disease >2 cm in the platinum+paclitaxel group (50% versus 24%), (p = 0.04). However, progression-free survival was similar in both groups irrespective of stage or residual volume of disease. Therefore consideration to selective use of paclitaxel could reduce patient morbidity and costs significantly.

  9. CAF01 adjuvant increases the protection conferred by a commercially available influenza split vaccine in a ferret model

    DEFF Research Database (Denmark)

    Martel, Cyril; Jensen, Trine Hammer; Nielsen, Lars Peter

    , we compared the immune response in ferrets vaccinated with a commercial influenza split vaccine with the same vaccine mixed with the CAF01 adjuvant and furthermore used two recently circulating H1N1 viruses for the challenge of the animals. We investigated antibody levels in serum and nasal washes......The immunogenicity and efficacy of preventive vaccines against influenza are considered suboptimal and the development of novel influenza vaccination strategies is urgently needed. Commercially available trivalent split vaccines are known to elicit mainly a humoral immune response, whereas...... by ELISA, as well as IFN-gamma production by peripheral blood lymphocytes by FACS, and virus excretion by RT-PCR. CAF01 improved the immunogenicity of the vaccine, increasing the specific IgA and IgG levels as well as triggering cellular-mediated immunity. The adjuvant also enhanced the protection...

  10. A novel non-mineral oil-based adjuvant. II. Efficacy of a synthetic sulfolipopolysaccharide in a squalane-in-water emulsion in pigs

    NARCIS (Netherlands)

    L.A.Th. Hilgers (L. A Th); P.L.I. Platenburg (P. L I); A. Luitjens (A.); B. Groenveld (B.); T. Dazelle (T.); J.T.M. Weststrate

    1994-01-01

    textabstractThe adjuvanticity of a sulfolipopolysaccharide (SLP) incorporated into a squalane-in-water emulsion (SLP/S/W) was compared with that of a mineral oil-in-water (O/W) adjuvant currently used in commercial porcine vaccines. Groups of pigs were immunized twice with vaccines comprising either

  11. Improved Outcome of High-Grade, Early 1-Stage Endometrioid Endometrial Carcinoma With Adjuvant Chemotherapy and Radiotherapy: Comparison of 2 Treatment Strategies

    NARCIS (Netherlands)

    Reynaers, E.A.; Jutzi, L.; Ezendam, N.P.; Kwon, J.S.; Pijnenborg, J.M.A.

    2017-01-01

    OBJECTIVE: Patients with high-grade endometrioid endometrial carcinoma have a high risk of recurrence, even in early stage. To determine the benefit of a more aggressive adjuvant treatment approach, different treatment strategies of 2 referral centers were compared. MATERIALS AND METHODS: Outcome of

  12. Prospective study of long-term impact of adjuvant high-dose and conventional-dose chemotherapy on health-related quality of life

    NARCIS (Netherlands)

    Buijs, C.; Rodenhuis, S.; Seynaeve, C.M.; van Hoesel, Q.G.; van der Wall, E.; Smit, W.J.; Nooij, M.A.; Voest, E.; Hupperets, P.; TenVergert, E.M.; van Tinteren, H.; Willemse, P.H.; Mourits, M.J.; Aaronson, N.K.; Post, W.J.; de Vries, E.G.

    2007-01-01

    Purpose To evaluate and compare health-related quality of life (HRQOL) after conventional- and high-dose adjuvant chemotherapy in patients with high-risk breast cancer. Patients and Methods Patients were randomly assigned to either a conventional or high-dose chemotherapy regimen; both regimens were

  13. Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n=647) with primary breast cancer

    DEFF Research Database (Denmark)

    Willemoe, Gro L.; Hertel, Pernille Bræmer; Bartels, Annette;

    2009-01-01

    PURPOSE: A number of prospective studies have shown that adjuvant CEF significantly improves disease-free and overall survival as compared to CMF in breast cancer patients. Our aim was to determine whether the benefit of epirubicin versus methotrexate differs according to TIMP-1 tumour cell...

  14. Body mass index at diagnosis and survival among colon cancer patients enrolled in clinical trials of adjuvant chemotherapy.

    Science.gov (United States)

    Sinicrope, Frank A; Foster, Nathan R; Yothers, Greg; Benson, Al; Seitz, Jean Francois; Labianca, Roberto; Goldberg, Richard M; Degramont, Aimery; O'Connell, Michael J; Sargent, Daniel J

    2013-04-15

    Although obesity is an established risk factor for developing colon cancer, its prognostic impact and relation to patient sex in colon cancer survivors remains unclear. The authors examined the prognostic and predictive impact of the body mass index (BMI) in patients with stage II and III colon carcinoma (N = 25,291) within the Adjuvant Colon Cancer Endpoints (ACCENT) database. BMI was measured at enrollment in randomized trials of 5-fluorouracil-based adjuvant chemotherapy. Association of BMI with the time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) were determined using Cox regression models. Statistical tests were 2-sided. During a median follow-up of 7.8 years, obese and underweight patients had significantly poorer survival compared with overweight and normal-weight patients. In a multivariable analysis, the adverse prognostic impact of BMI was observed among men but not among women (Pinteraction = .0129). Men with class 2 and 3 obesity (BMI ≥ 35.0 kg/m(2) ) had a statistically significant reduction in DFS (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01-1.33; P = .0297) compared with normal-weight patients. Underweight patients had a significantly shorter TTR and reduced DFS (HR, 1.18; 95% CI, 1.09-1.28; P Obesity and underweight status were associated independently with inferior outcomes in patients with colon cancer who received treatment in adjuvant chemotherapy trials. Copyright © 2013 American Cancer Society.

  15. Evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine.

    Science.gov (United States)

    Mangal, Sharad; Pawar, Dilip; Agrawal, Udita; Jain, Arvind K; Vyas, Suresh P

    2014-02-01

    The aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (A-CHMp) for oral vaccine against anthrax. The zeta potential of A-CHMp was -29.7 mV, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. The results indicated that A-CHMp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. The immunization studies indicated that A-CHMp resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response. Thus, A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax.

  16. Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants

    Directory of Open Access Journals (Sweden)

    Marie-Ève Lebel

    2015-08-01

    Full Text Available Vaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; as such, these challenges have driven the emergence of novel vaccine design approaches. In this regard, much effort has been put into the development of new safe adjuvants and vaccine platforms. Of particular interest, the utilization of plant virus-like nanoparticles and recombinant plant viruses has gained increasing significance as an effective tool in the development of novel vaccines against infectious diseases and cancer. The present review summarizes recent advances in the use of plant viruses as nanoparticle-based vaccines and adjuvants and their mechanism of action. Harnessing plant-virus immunogenic properties will enable the design of novel, safe, and efficacious prophylactic and therapeutic vaccines against disease.

  17. Antifungal adjuvants: Preserving and extending the antifungal arsenal.

    Science.gov (United States)

    Butts, Arielle; Palmer, Glen E; Rogers, P David

    2017-02-17

    As the rates of systemic fungal infections continue to rise and antifungal drug resistance becomes more prevalent, there is an urgent need for new therapeutic options. This issue is exacerbated by the limited number of systemic antifungal drug classes. However, the discovery, development, and approval of novel antifungals is an extensive process that often takes decades. For this reason, there is growing interest and research into the possibility of combining existing therapies with various adjuvants that either enhance activity or overcome existing mechanisms of resistance. Reports of antifungal adjuvants range from plant extracts to repurposed compounds, to synthetic peptides. This approach would potentially prolong the utility of currently approved antifungals and mitigate the ongoing development of resistance.

  18. Adjuvant postoperative radiotherapy for gastric carcinoma with poor prognostic signs.

    Science.gov (United States)

    Slot, A; Meerwaldt, J H; van Putten, W L; Treurniet-Donker, A D

    1989-12-01

    Fifty-seven patients with poor prognostic factors following resection with curative intent for gastric adenocarcinoma (T3 or T4, positive lymph nodes, positive resection line) received adjuvant radiotherapy. A dose of 30.0-50.0 Gy was given in 10-25 fractions in one course or with a split of 2 weeks after 15 fractions. This was combined with 5-fluorouracil (5-FU) (375 mg/m2) given i.v. as a bolus during the first 4 days of radiation (n = 49). The 5-year survival was 26%; this rate is higher than the figures mentioned in the literature after surgery alone. The only way to prove the role of adjuvant radiotherapy for gastric carcinoma is a prospective randomized trial.

  19. [Stomach carcinoma. Optimizing therapy by neoadjuvant or adjuvant therapy?].

    Science.gov (United States)

    Rosen, H

    1999-01-01

    Despite the decreasing frequency of gastric cancer in most Western countries prognosis could not be improved by surgery alone in the past. Advanced tumor stage due to late diagnosis is one of the reasons for this observation. Contrary to breast and colorectal cancer, postoperative chemotherapy failed to improve prognosis in gastric cancer. Small number of patients in Western studies, insufficient surgical procedures and the high frequency of locoregional relapse may be attributed for this observation. Intraperitoneal, adjuvant chemotherapy showed a positive impact on survival in Asian studies only, but was also used successfully as a part of a multimodality approach in Western phase II trials. Since neoadjuvant therapy proved to create downstaging of tumor size in some patients with advanced gastric cancer some working groups tried to influence prognosis of potentially resectable tumors by preoperative chemotherapy, surgical resection and postoperative, adjuvant therapy in the recent past. However, the efficacy of this therapeutic approach has to be reconfirmed in a controlled, phase III fashion.

  20. Adjuvant postoperative radiotherapy for gastric carcinoma with poor prognostic signs

    Energy Technology Data Exchange (ETDEWEB)

    Slot, A.; Meerwaldt, J.H.; Treurniet-Donker, A.D. (Dr. Daniel Den Hoed Cancer Center, Rotteram (Netherlands). Department of Radiotherapy); Putten, W.L.J. van (Dr. Daniel Den Hoed Cancer Center, Rotterdam (Netherlands). Department of Statistics)

    1989-12-01

    Fifty-seven patients with poor prognostic factors following resection with curative intent for gastric adenocarcinoma T{sub 3} or T{sub 4}, positive lymph nodes, positive resection line received adjuvant radiotherapy. A dose of 30.0-50.0 Gy was given in 10-25 fraction in one course or with a split of 2 weeks after 15 fractions. This was combined with 5-fluorouracil (5-FU) (375 mg/m{sup 2}) given i.v. as a bolus during the first 4 days of radiation (n = 49). The 5-year survival was 26%; this rate is higher than the figures mentioned in the literature after surgery alone. The only way to prove the role of adjuvant radiotherapy for gastric carcinoma is a prospective randomized trial. (author). 11 refs., 2 figs., 6 tabs.

  1. [How I treat colorectal cancer. I. Prevention and adjuvant treatment].

    Science.gov (United States)

    Bours, V; Jerusalem, G; Fillet, G

    1998-04-01

    Colorectal adenocarcinoma is a major cause of cancer-related morbidity and mortality in Belgium and in other western countries. Prevention implies a modification of alimentation and maybe a chronic uptake of acetylsalicylic acid. Treatment of colorectal cancers is based on surgery and the prognosis is determined by the locoregional or metastatic tumor spread. Complete resection of any Astler Coller stage C colorectal malignant tumor has to be followed by a 5-fluorouracil-based adjuvant chemotherapy. In these protocols, 5-fluorouracil is administered together with folinic acid or levamisole. The administration of an adjuvant chemotherapy could also be considered for stage BII diseases. As rectal cancers are characterized by high local relapse rates, their treatment should associate radiotherapy, given either post-surgery or preferentially pre-surgery, with resection and chemotherapy. Appropriate treatment of colorectal cancers thus requires a concerted multidisciplinary approach.

  2. Antibiotic adjuvants - A strategy to unlock bacterial resistance to antibiotics.

    Science.gov (United States)

    González-Bello, Concepción

    2017-09-15

    Resistance to available antibiotics in pathogenic bacteria is currently a global challenge since the number of strains that are resistant to multiple types of antibiotics has increased dramatically each year and has spread worldwide. To unlock this problem, the use of an 'antibiotic adjuvant' in combination with an antibiotic is now being exploited. This approach enables us to prolong the lifespan of these life-saving drugs. This digests review provides an overview of the main types of antibiotic adjuvants, the basis of their operation and the remaining issues to be tackled in this field. Particular emphasis is placed on those compounds that are already in clinical development, namely β-lactamase inhibitors. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  3. Evaluation of the immunoprophylactic potential of a killed vaccine candidate in combination with different adjuvants against murine visceral leishmaniasis.

    Science.gov (United States)

    Thakur, Ankita; Kaur, Harpreet; Kaur, Sukhbir

    2015-02-01

    Despite a large number of field trials, till date no prophylactic antileishmanial vaccine exists for human use. Killed antigen formulations offer the advantage of being safe but they have limited immunogenicity. Recent research has documented that efforts to develop effective Leishmania vaccine have been limited due to the lack of an appropriate adjuvant. Addition of adjuvants to vaccines boosts and directs the immunogenicity of antigens. So, the present study was done to evaluate the effectiveness of four adjuvants i.e. alum, saponin, cationic liposomes and monophosphoryl lipid-A in combination with Autoclaved Leishmania donovani (ALD) antigen against murine visceral leishmaniasis (VL). BALB/c mice were immunized thrice with respective vaccine formulation. Two weeks after last booster, challenge infection was given. Mice were sacrificed 15 days after last immunization and on 30, 60 and 90 post infection/challenge days. A considerable protective efficacy was shown by all vaccine formulations. It was evident from significant reduction in parasite load, profound delayed type hypersensitivity responses (DTH), increased IgG2a titres and high levels of Th1 cytokines (IFN-γ, IL-12) as compared to the infected controls. However, level of protection varied with the type of adjuvant used. Maximum protection was achieved with the use of liposome encapsulated ALD antigen and it was closely followed by group immunized with ALD+MPL-A. Significant results were also obtained with ALD+saponin, ALD+alum and ALD antigen (alone) but the protective efficacy was reduced as compared to other immunized groups. The present study reveals greater efficacy of two vaccine formulations i.e. ALD+liposome and ALD+MPL-A against murine VL.

  4. Preparation and evaluation of functional foods in adjuvant arthritis

    OpenAIRE

    2012-01-01

    Adjuvant arthritis is an animal model that closely resembles rheumatoid arthritis in humans. It is a successful working model used to study new anti-inflammatory agents. In previous studies (animal and clinical) we have shown that evening primrose oil, fish oil and the methanol extract of date fruits and fenugreek seeds have anti-inflammatory activity and that the methanol extract of dates has an antioxidant effect. Based on these studies, the aim of the present study was to prepare 7 functio...

  5. Adjuvants to local anesthetics: Current understanding and future trends

    Science.gov (United States)

    Swain, Amlan; Nag, Deb Sanjay; Sahu, Seelora; Samaddar, Devi Prasad

    2017-01-01

    Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids (dexamethasone), anti-inflammatory agents (parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action (tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability (liposomal

  6. Hypothesis: Silver Nanoparticles as an Adjuvant for Cancertherapy

    Directory of Open Access Journals (Sweden)

    Ramin Mohammadzadeh

    2012-06-01

    Full Text Available Cytotoxic agents are a main part of therapeutic process against the observed tumors, which lead to some unwished damages, due to drug uptake by normal body cells causing various tissue/organ failures associated with formal administration manners. But nowadays the risk is reduced by new target therapy techniques, of which the observed physical nature of micelles and nanosilver particles, governing their special behavior, could help using micelle-coated silver nanoparticles as a novel adjuvant for cancer target therapy.

  7. Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

    Directory of Open Access Journals (Sweden)

    Ivana Škrnjug

    Full Text Available The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

  8. [Adjuvant chemotherapy in colon cancer. About 119 cases].

    Science.gov (United States)

    Yaich, Asma; Khanfir, Afef; Bayrouti, Mohamed Issam; Frikha, Mounir

    2015-04-01

    colon cancer is a public health problem worldwide and in Tunisia. The prognosis of patients with unresectable colorectal cancer varies according to the stage. The indication for adjuvant chemotherapy is well established in the colon cancer stage III, while it remains a matter of controversy for stage II. The aim of this work is to identify the epidemiological and anatomoclinical assess therapeutic outcomes in terms of overall survival of patients with high-risk stage II and stage III colon cancer treated with surgery and adjuvant chemotherapy. DS: It's a retrospective study based on 119 patients with colon adenocarcinoma from 1996 to 2010. This patients suffering from colon cancer classified stage II and III having them all radical surgery and adjuvant chemotherapy. The average age of our patients was 53 years. The surgery was performed in an emergency situation in 53 patients (44%). Stages II and III, respectively, were observed in 47% and 53% of cases. Three regimens of chemotherapy were used: protocol FUFOL (50%), followed by FOLFOX (34%) and the protocol LV5FU2 (16%). Overall survival of patients all stages combined was 73.4% at 5 years. Stage III of the TNM classification (p = 0.03) and the number of cycles of chemotherapy colon cancer is improving thanks to recent advances that have enabled the integration of new cytogenetic factors in the therapeutic decision.

  9. [Development of Nucleic Acid-Based Adjuvant for Cancer Immunotherapy].

    Science.gov (United States)

    Kobiyama, Kouji; Ishii, Ken J

    2015-09-01

    Since the discovery of the human T cell-defined tumor antigen, the cancer immunotherapy field has rapidly progressed, with the research and development of cancer immunotherapy, including cancer vaccines, being conducted actively. However, the disadvantages of most cancer vaccines include relatively weak immunogenicity and immune escape or exhaustion. Adjuvants with innate immunostimulatory activities have been used to overcome these issues, and these agents have been shown to enhance the immunogenicity of cancer vaccines and to act as mono-therapeutic anti-tumor agents. CpG ODN, an agonist for TLR9, is one of the promising nucleic acid-based adjuvants, and it is a potent inducer of innate immune effector functions. CpG ODN suppresses tumor growth in the absence of tumor antigens and peptide administration. Therefore, CpG ODN is expected to be useful as a cancer vaccine adjuvant as well as a cancer immunotherapy agent. In this review, we discuss the potential therapeutic applications and mechanisms of CpG ODN for cancer immunotherapy.

  10. Adherence to adjuvant endocrine therapy in women with breast cancer.

    Science.gov (United States)

    Danilak, Melanie; Chambers, Carole R

    2013-06-01

    To determine how many breast cancer patients who initiated adjuvant endocrine therapy discontinued early and to evaluate adherence in patients who persisted with therapy. Secondary objectives were to explore possible trends to see if certain factors may correlate to early discontinuation of therapy. A retrospective review of charts and pharmacy dispensing records was conducted, including patients who initiated adjuvant endocrine therapy for breast cancer at the Cross Cancer Institute from 1 January to 31 December, 2006. Out of 346 patients, 81 (22%) discontinued therapy within 2 years. Adherence rates calculated for the 265 patients who remained on therapy beyond 2 years showed that 247 (93%) of these patients had 80% or better adherence. Patients who did not undergo chemotherapy and patients with Cross Cancer Institute follow-up times of less than 1 year were significantly more likely to discontinue therapy early. The majority of patients who were prescribed adjuvant endocrine therapy for breast cancer at the Cross Cancer Institute remained on therapy for at least 2 years and were adherent. Longer follow-up by Cross Cancer Institute practitioners may help decrease discontinuation rates.

  11. Freund's vaccine adjuvant promotes Her2/Neu breast cancer

    Directory of Open Access Journals (Sweden)

    Woditschka Stephan

    2009-01-01

    Full Text Available Abstract Background Inflammation has been linked to the etiology of many organ-specific cancers. Indirect evidence suggests a possible role for inflammation in breast cancer. We investigated whether the systemic inflammation induced by Freund's adjuvant (FA promotes mammary carcinogenesis in a rat model in which cancer is induced by the neu oncogene. Methods The effects of FA on hyperplastic mammary lesions and mammary carcinomas were determined in a neu-induced rat model. The inflammatory response to FA treatment was gauged by measuring acute phase serum haptoglobin. In addition, changes in cell proliferation and apoptosis following FA treatment were assessed. Results Rats receiving FA developed twice the number of mammary carcinomas as controls. Systemic inflammation following FA treatment is chronic, as shown by a doubling of the levels of the serum biomarker, haptoglobin, 15 days following initial treatment. We also show that this systemic inflammation is associated with the increased growth of hyperplastic mammary lesions. This increased growth results from a higher rate of cellular proliferation in the absence of changes in apoptosis. Conclusion Our data suggests that systemic inflammation induced by Freund's adjuvant (FA promotes mammary carcinogenesis. It will be important to determine whether adjuvants currently used in human vaccines also promote breast cancer.

  12. Neisseria lactamica antigens complexed with a novel cationic adjuvant.

    Science.gov (United States)

    Gaspar, Emanuelle B; Rosetti, Andreza S; Lincopan, Nilton; De Gaspari, Elizabeth

    2013-03-01

    Colonization of the nasopharynx by non-pathogenic Neisseria species, including N. lactamica, has been suggested to lead to the acquisition of natural immunity against Neisseria meningitidis in young children. The aim of this study was to identify a model complex of antigens and adjuvant for immunological preparation against N. meningitidis B, based on cross reactivity with N. lactamica outer membrane vesicles (OMV) antigens and the (DDA-BF) adjuvant. Complexes of 25 µg of OMV in 0.1 mM of DDA-BF were colloidally stable, exhibiting a mean diameter and charge optimal for antigen presentation. Immunogenicity tests for these complexes were performed in mice. A single dose of OMV/DDA-BF was sufficient to induce a (DTH) response, while the same result was achieved only after two doses of OMV/alum. In addition, to achieve total IgG levels that are similar to a single immunization with OMV/DDA-BF, it was necessary to give the mice a second dose of OMV/alum. Moreover, the antibodies induced from a single immunization with OMV/DDA-BF had an intermediate avidity, but antibodies with a similar avidity were only induced by OMV/alum after two immunizations. The use of this novel cationic adjuvant for the first time with a N. lactamica OMV preparation revealed good potential for future vaccine design.

  13. Adjuvant radiotherapy for stage I endometrial cancer: systematic review and meta-analysis.

    Science.gov (United States)

    Kong, A; Simera, I; Collingwood, M; Williams, C; Kitchener, H

    2007-10-01

    The role of adjuvant radiotherapy in stage I endometrial cancer following surgery remains unclear. The management for these patients varies widely, particularly in stage I patients with different risk factors. Using the methodology of Cochrane Collaboration, we did a systematic and meta-analysis of all know randomised controlled trials which compared adjuvant radiotherapy versus no radiotherapy following surgery for patients with stage I endometrial cancer. The meta-analysis was carried out on four trials (three published and one unpublished) and a total of 1770 patients. The addition of pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a relative risk (RR) of 0.28 [95% confidence interval (CI) 0.17-0.44, P endometrial cancer death or distant recurrence. A subgroup analysis showed a trend towards the reduction in the risks of death from all causes and endometrial cancer in patients with multiple high risk factors (including stage 1c and grade 3). External beam pelvic radiotherapy should be considered in patients with multiple high-risk features including stage 1c and grade 3. However, it carries an inherent risk of damage and toxicity and should be avoided in stage 1 endometrial cancer patients with no high risk factors.

  14. The cost utility and budget impact of adjuvant racecadotril for acute diarrhea in children in Thailand.

    Science.gov (United States)

    Rautenberg, Tamlyn Anne; Zerwes, Ute

    2017-01-01

    To evaluate the cost utility and the budget impact of adjuvant racecadotril for the treatment of acute diarrhea in children in Thailand. A cost utility model has been adapted to the context of Thailand to evaluate racecadotril plus oral rehydration solution (R+ORS) versus oral rehydration solution (ORS) alone for acute diarrhea in children costs and effects (quality-adjusted life years) over a 6-day time horizon from a public health care payer's perspective in Thailand. Deterministic sensitivity analysis and budget impact analysis have been undertaken. According to the cost utility model, the intervention (R+ORS) is less costly and more effective than the comparator (ORS) for the base case with a dominant incremental cost-effectiveness ratio of -2,481,390฿ for the intervention. According to the budget impact analysis (assuming an increase of 5% market share for R+ORS over 5 years), the year-on-year reduction for diarrhea as a percentage of the total health care expenditure is -0.0027%, resulting in potential net cost savings of -35,632,482฿ over 5 years. Subject to the assumptions and limitations of the models, adjuvant racecadotril versus ORS alone is potentially cost-effective for children in Thailand and uptake could translate into savings for the Thailand public health care system.

  15. Zn- and Mg- Containing Tricalcium Phosphates-Based Adjuvants for Cancer Immunotherapy

    Science.gov (United States)

    Wang, Xiupeng; Li, Xia; Onuma, Kazuo; Sogo, Yu; Ohno, Tadao; Ito, Atsuo

    2013-07-01

    Zn-, and Mg-containing tricalcium phosphates (TCPs) loaded with a hydrothermal extract of a human tubercle bacillus (HTB) were prepared by immersing Zn-TCP and Mg-TCP in HTB-containing supersaturated calcium phosphate solutions. The in vitro and in vivo immunogenic activities of the HTB-loaded Zn-, and Mg-TCPs (Zn-Ap-HTB and Mg-Ap-HTB, respectively) were evaluated as potential immunopotentiating adjuvants for cancer immunotherapy. The Zn-Ap-HTB and Mg-Ap-HTB adjuvants showed no obvious cytotoxicity and more effectively stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion by macrophage-like cells than unprocessed HTB or HTB-loaded TCP (T-Ap-HTB) in vitro. Zn-Ap-HTB and Mg-Ap-HTB mixed with liquid-nitrogen-treated tumor tissue markedly inhibited the in vivo development of rechallenged Lewis lung carcinoma (LLC) cells compared with T-Ap-HTB and the unprocessed HTB mixed liquid-nitrogen-treated tumor tissue. Zn-Ap-HTB and Mg-Ap-HTB contributed to eliciting potent systemic antitumor immunity in vivo.

  16. Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Youssef Al-Tonbary

    2009-01-01

    Full Text Available Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX antioxidant enzyme, malondialdehyde (MDA, tumor necrosis factor- (TNF-, liver enzymes, and bone marrow picture. Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment.

  17. Establishment of a Rat Adjuvant Arthritis-Interstitial Lung Disease Model

    Directory of Open Access Journals (Sweden)

    Liu-nan Song

    2016-01-01

    Full Text Available Introduction. Development of an animal model of rheumatoid arthritis-interstitial lung disease (RA-ILD and improved knowledge of the pathogenesis of RA-ILD may facilitate earlier diagnosis and the development of more effective targeted therapies. Methods. Adult male Wistar rats were studied in an adjuvant arthritis (AA model induced by the injection of Freund’s complete adjuvant (FCA. Rats were sacrificed on days 7, 14, 21, and 28 after FCA injection. Lung tissue was obtained for histopathological examination and evaluation of Caveolin-1 (Cav-1 and transforming growth factor-β (TGF-β1 protein expression levels. Results. Pulmonary inflammation was evident in lung tissue from day 21 after FCA injection. Inflammation and mild fibrosis were observed in lung tissue on day 28 after FCA injection. Cav-1 protein expression was significantly decreased from day 7 through day 28 and TGF-β1 protein expression was significantly increased on day 28 after FCA injection compared to control (P<0.05. Conclusion. We established an AA rat model that exhibited the extra-articular complication of RA-ILD. We identified Cav-1 and TGF-β1 as protein biomarkers of RA-ILD in this model and propose their signaling pathway as a possible target for therapeutic intervention.

  18. Influence of Asian dust particles on immune adjuvant effects and airway inflammation in asthma model mice.

    Directory of Open Access Journals (Sweden)

    Jun Kurai

    Full Text Available An Asian dust storm (ADS contains airborne particles that affect conditions such as asthma, but the mechanism of exacerbation is unclear. The objective of this study was to compare immune adjuvant effects and airway inflammation induced by airborne particles collected on ADS days and the original ADS soil (CJ-1 soil in asthma model mice.Airborne particles were collected on ADS days in western Japan. NC/Nga mice were co-sensitized by intranasal instillation with ADS airborne particles and/or Dermatophagoides farinae (Df, and with CJ-1 soil and/or Df for 5 consecutive days. Df-sensitized mice were stimulated with Df challenge intranasally at 7 days after the last Df sensitization. At 24 hours after challenge, serum allergen specific antibody, differential leukocyte count and inflammatory cytokines in bronchoalveolar lavage fluid (BALF were measured, and airway inflammation was examined histopathologically.Co-sensitization with ADS airborne particles and Df increased the neutrophil and eosinophil counts in BALF. Augmentation of airway inflammation was also observed in peribronchiolar and perivascular lung areas. Df-specific serum IgE was significantly elevated by ADS airborne particles, but not by CJ-1 soil. Levels of interleukin (IL-5, IL-13, IL-6, and macrophage inflammatory protein-2 were higher in BALF in mice treated with ADS airborne particles.These results suggest that substances attached to ADS airborne particles that are not in the original ADS soil may play important roles in immune adjuvant effects and airway inflammation.

  19. Effects of oral administration of type Ⅱ collagen on adjuvant arthritis in rat sand its mechanisms

    Institute of Scientific and Technical Information of China (English)

    胡永秀; 赵文明; 钱娴娟; 张力平

    2003-01-01

    Objective To investigate the effects of oral administration of type Ⅱ collagen (CⅡ) on a djuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CⅡ with those of the Chinese traditional medicine Tripterygium Polyglycoside a dministered similarly.Methods Arthritis was induced in rats by immunization using Freund's complete adjuvant (FCA). After feeding rats either soluble CⅡ or Tripterygium Polyglycoside, chan ges in degree of articular swelling and articular histological findings were observed in AA rats. Some correlative immunological indexes were measured, includi ng delayed type hypersensitivity (DTH) reaction, anti-collagen and anti-Mycoba cterium tuberculosis (MT) antibody in serum, and levels of IFN-γ and TNF-α i n articular steep in rats.Results Oral administration of CⅡ was able to alleviate both distinctly articular and general symptoms in AA rats, suppress synovium hyperplasia and inflammatory cells infiltration in arthrosis capsule. The effects brought about by CⅡ were stronger than those by Tripterygium Polyglycoside. Oral administration of CⅡ inhibi ted antigen-specific immune response, such as DTH and antibody reaction to CⅡ . In addition, the expression of IFN-γ and TNF-α in joints were locally dow nregulated. Conclusions The therapeutic effect of oral administration of CⅡ is obvious on adjuvant art hritis in rats. Its remedial mechanisms are likely related to the downregulation of both IFN-γ and TNF-α, and the suppression of cell immunity.

  20. Efficacy of spirulina as an antioxidant adjuvant to corticosteroid injection in management of oral submucous fibrosis.

    Science.gov (United States)

    Shetty, Prathima; Shenai, Prashanth; Chatra, Laxmikanth; Rao, Prasanna Kumar

    2013-01-01

    Oral submucous fibrosis (OSF) is a chronic condition of the oral cavity which results in permanent disability. A number of studies have proven that the management of premalignant diseases should include antioxidants. Therefore, a study was carried out to evaluate the efficacy of spirulina as an antioxidant adjuvant to corticosteroid injections in the management of 40 oral submucous fibrosis subjects of south Karnataka and north Kerala. An intervention study was conducted on 40 oral submucous fibrosis cases, 40 patients were divided into two groups, group A (spirulina group) and group B (placebo group). Group A received spirulina 500 mg twice daily and biweekly intralesional steroid injection of Betamethasone 4 mg/ml for 3 months and group B was given placebo capsules twice daily and biweekly intralesional steroid injection of Betamethasone 4 mg/ml for 3 months. The results were analyzed with the paired "t" test and the unpaired "t" test. Clinical improvements in mouth opening was significant in the posttreatment period in both Spirulina and placebo groups. Both the groups showed statistically significant reduction in burning sensation. However, when both groups were compared, mouth opening and burning sensation was found to be statistically very highly significant in favor of the spirulina group. Spirulina can bring about clinical improvements in OSF patients. The observed effects suggest that spirulina can be used as an adjuvant therapy in the initial management of OSF patients. However, studies involving larger samples and longer period of treatment follow up are suggested in the future.

  1. Alphavirus replicon-based adjuvants enhance the immunogenicity and effectiveness of Fluzone ® in rhesus macaques.

    Science.gov (United States)

    Carroll, Timothy D; Matzinger, Shannon R; Barro, Mario; Fritts, Linda; McChesney, Michael B; Miller, Christopher J; Johnston, Robert E

    2011-01-29

    Venezuelan equine encephalitis virus replicon particles (VRP) without a transgene (null VRP) have been used to adjuvant effective humoral [1], cellular [2], and mucosal [3] immune responses in mice. To assess the adjuvant activity of null VRP in the context of a licensed inactivated influenza virus vaccine, rhesus monkeys were immunized with Fluzone(®) alone or Fluzone(®) mixed with null VRP and then challenged with a human seasonal influenza isolate, A/Memphis/7/2001 (H1N1). Compared to Fluzone(®) alone, Fluzone(®)+null VRP immunized animals had stronger influenza-specific CD4(+) T cell responses (4.4 fold) with significantly higher levels of virus-specific IFN-γ (7.6 fold) and IL-2 (5.3 fold) producing CD4+ T cells. Fluzone(®)+null VRP immunized animals also had significantly higher plasma anti-influenza IgG (pVRP immunization was 1.2 log greater (pVRP immunized monkeys had a significantly lower level of viral replication (pVRP immunized monkeys immediately after challenge. There were significant inverse correlations between influenza RNA levels in tracheal lavages and plasma anti-influenza HI and IgG anti-influenza antibody titers prior to challenge. These results demonstrate that null VRP dramatically improve both the immunogenicity and protection elicited by a licensed inactivated influenza vaccine. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Chemically modified inulin microparticles serving dual function as a protein antigen delivery vehicle and immunostimulatory adjuvant.

    Science.gov (United States)

    Gallovic, Matthew D; Montjoy, Douglas G; Collier, Michael A; Do, Clement; Wyslouzil, Barbara E; Bachelder, Eric M; Ainslie, Kristy M

    2016-03-01

    To develop a new subunit vaccine adjuvant, we chemically modified a naturally-occurring, immunostimulatory inulin polysaccharide to produce an acid-sensitive biopolymer (acetalated inulin, Ace-IN). Various hydrophobic Ace-IN polymers were formed into microparticles (MPs) by oil-in-water emulsions followed by solvent evaporation These Ace-IN MPs possessed tunable degradation characteristics that, unlike polyesters used in FDA-approved microparticulate formulations, had only pH-neutral hydrolytic byproducts. Macrophages were passively targeted with cytocompatible Ace-IN MPs. TNF-α production by macrophages treated with Ace-IN MPs could be altered by adjusting the polymers' chemistry. Mice immunized with Ace-IN MPs encapsulating a model ovalbumin (OVA) antigen showed higher production of anti-OVA IgG antibody levels relative to soluble antigen. The antibody titers were also comparable to an alum-based formulation. This proof-of-concept establishes the potential for chemically-modified inulin MPs to simultaneously enable dual functionality as a stimuli-controlled antigen delivery vehicle and immunostimulatory adjuvant.

  3. External validation of Adjuvant! Online breast cancer prognosis tool. Prioritising recommendations for improvement.

    Directory of Open Access Journals (Sweden)

    David Hajage

    Full Text Available BACKGROUND: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors. PATIENTS AND METHODS: The French data set is composed of 456 women with early breast cancer. The Dutch data set is composed of 295 women less than 52 years of age. Agreement between observation and Adjuvant! Online prediction was checked, and logistic models were performed to estimate the prognostic information added by risk factors to Adjuvant! Online prediction. RESULTS: Adjuvant! Online prediction was overall well-calibrated in the French data set but failed in some subgroups of such high grade and HER2 positive patients. HER2 status, Mitotic Index and Ki67 added significant information to Adjuvant! Online prediction. In the Dutch data set, the overall 10-year survival was overestimated by Adjuvant! Online, particularly in patients less than 40 years old. CONCLUSION: Adjuvant! Online needs to be updated to adjust overoptimistic results in young and high grade patients, and should consider new predictors such as Ki67, HER2 and Mitotic Index.

  4. The Quest for an HIV-1 Vaccine Adjuvant: Bacterial Toxins as New Potential Platforms.

    Science.gov (United States)

    Nashar, Toufic O

    2014-06-01

    While tremendous efforts are undergoing towards finding an effective HIV-1 vaccine, the search for an HIV-1 vaccine adjuvant lags behind and is understudied. More recently, however, efforts have focused on testing adjuvant formulations that can boost the immune response and generate broadly neutralizing antibodies to HIV-1 ENV (gp160). Despite this, there remain a number of challenges towards achieving this goal. These include safety of adjuvant formulations; stability of the incorporated antigens; maintenance of ENV immunogenicity; optimal inoculation sites; the effective combination of adjuvants; stability of ENV neutralizing epitopes in some adjuvant formulations; mucosal immunity; and long-term maintenance of the immune response. A new class of adjuvants for HIV-1 proteins is suggested to overcome many of the limitations of some other adjuvants. Type 1 (LT-I) and type 2 (LT-II) human E. coli enterotoxins (HLTs) and their non-toxic B-subunits derivatives are strong systemic and mucosal adjuvants and effective carriers for other proteins and epitopes. Their stable molecular structure in the presence of fused proteins and epitopes, and their ability to target surface receptors on antigen presenting cells make them ideal for the delivery of HIV-1 ENV or HIV other proteins. Importantly, unlike some other adjuvants, HLTs and derivatives have well-defined modes of immune system activation. The challenges in finding optimal HIV-1 vaccine adjuvant formulation and the important properties of HLTs are discussed.

  5. The effects of CpG-ODNs and Chitosan adjuvants on the elicitation of immune responses induced by the HIV-1-Tat-based candidate vaccines in mice.

    Science.gov (United States)

    Alipour, Samira; Mahdavi, Atiyeh; Abdoli, Asghar

    2017-03-01

    HIV1-Tat-based vaccines could elicit broad, durable and neutralizing immune responses and are considered as potential AIDS vaccines. The present study aims to formulate CpG-ODNs adjuvant and Chitosan with Tat protein to enhance the immunogenicity of HIV-1-Tat-based candidate vaccines and to investigate their efficacies in mice. To this end, we added CpG-ODNs, Chitosan and Alum as adjuvants to the Tat-based candidate vaccine formulations. Then, we compared frequency and magnitude of both humoral and cellular immune responses from mice immunized with the adjuvant-formulated Tat candidate vaccines against those obtained from mice immunized with recombinant Tat protein alone. Mice were subcutaneously immunized three times at 2-week intervals with the candidate vaccines. Measurements of anti-Tat immune responses showed that all vaccinated groups had a good immunity compared to the control groups and developed high levels of both humoral and cellular responses. However, immunized mice with CpG-ODNs, and Chitosan-adjuvanted Tat vaccines elicited stronger T-cell responses (both humoral and cellular immunity) compared to the others. These data suggest that co-administration of recombinant Tat protein with CpG-ODNs and Chitosan may serve as a potential formulation for enhancing of the Tat vaccine-induced immunity and might have effects on shaping Th polarization induced by HIV1-Tat protein vaccines. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Anti-nicotine vaccines: Comparison of adjuvanted CRM197 and Qb-VLP conjugate formulations for immunogenicity and function in non-human primates.

    Science.gov (United States)

    McCluskie, Michael J; Thorn, Jennifer; Gervais, David P; Stead, David R; Zhang, Ningli; Benoit, Michelle; Cartier, Janna; Kim, In-Jeong; Bhattacharya, Keshab; Finneman, Jari I; Merson, James R; Davis, Heather L

    2015-12-01

    Anti-nicotine vaccines comprise nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). Unfortunately, those tested clinically have failed to improve overall long term quit rates. We had shown in mice that carrier, hapten, linker, hapten load (number of haptens per carrier molecule), aggregation and adducts, as well as adjuvants influence the function of antibodies (Ab) induced. Herein, we tested an optimized antigen, NIC7-CRM, comprised of 5-aminoethoxy-nicotine (NIC7) conjugated to genetically detoxified diphtheria toxin (CRM197), with hapten load of ~16, no aggregation (~100% monomer) and minimal adducts. NIC7-CRM was tested in non-human primates (NHP) and compared to NIC-VLP, which has the same hapten and carrier as the clinical-stage CYT002-NicQb but a slightly different linker and lower hapten load. With alum as sole adjuvant, NIC7-CRM was superior to NIC-VLP for Ab titer, avidity and ex vivo function (83% and 27% nicotine binding at 40ng/mL respectively), but equivalent for in vivo function after intravenous [IV] nicotine challenge (brain levels reduced ~10%). CpG adjuvant added to NIC7-CRM/alum further enhanced the Ab responses and both ex vivo function (100% bound) and in vivo function (~80% reduction in brain). Thus, both optimal antigen design and CpG adjuvant were required to achieve a highly functional vaccine. The compelling NHP data with NIC7-CRM with alum/CpG supported human testing, currently underway.

  7. MyD88 and TRIF synergistic interaction is required for TH1-cell polarization with a synthetic TLR4 agonist adjuvant.

    Science.gov (United States)

    Orr, Mark T; Duthie, Malcolm S; Windish, Hillarie Plessner; Lucas, Elyse A; Guderian, Jeffrey A; Hudson, Thomas E; Shaverdian, Narek; O'Donnell, Joanne; Desbien, Anthony L; Reed, Steven G; Coler, Rhea N

    2013-09-01

    Glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) is a synthetic adjuvant TLR4 agonist that promotes potent poly-functional T(H)1 responses. Different TLR4 agonists may preferentially signal via MyD88 or TIR-domain-containing adapter inducing IFN-beta (TRIF) to exert adjuvant effects; however, the contribution of MyD88 and TRIF signaling to the induction of polyclonal T(H)1 responses by TLR4 agonist adjuvants has not been studied in vivo. To determine whether GLA-SE preferentially signals through MyD88 or TRIF, we evaluated the immune response against a candidate tuberculosis (TB) vaccine Ag following immunization of mice lacking either signaling adapter compared with that of wild-type mice. We find that both MyD88 and TRIF are necessary for GLA-SE to induce a poly-functional T(H)1 immune response characterized by CD4(+) T cells producing IFN-γ, TNF, and IL-2, as well as IgG2c class switching, when paired with the TB vaccine Ag ID93. Accordingly, the protective efficacy of ID93/GLA-SE immunization against aerosolized Mycobacterium tuberculosis was lost when either signaling molecule was ablated. We demonstrate that MyD88 and TRIF must be expressed in the same cell for the in vivo T(H)1-skewing adjuvant activity, indicating that these two signaling pathways cooperate on an intracellular level. Thus engagement of both the MyD88 and TRIF signaling pathways are essential for the effective adjuvant activity of this TLR4 agonist. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Effect of alum co-adjuvantation of oil adjuvant vaccine on emulsion stability and immune responses against haemorhagic septicaemia in mice

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    Sujeet Kumar

    2015-10-01

    Full Text Available Background and Objectives: Haemorrhagic septicaemia (HS, caused by Pasteurella multocida, is the most important bacterial disease of cattle and buffaloes in India. Oil adjuvant vaccine (OAV is the most potent vaccine available for the control of HS. The study aims to evaluate the effect of alum co-adjuvantation of OAV on emulsion stability and immune response.Materials and Methods: Two different oil adjuvant vaccines viz., standard oil adjuvant vaccine (OAV and alum precipitated oil adjuvant vaccine (A–OAV were prepared with Pasteurella multocida antigen. Emulsion stability was tested by centrifugation, storage at 37 oC for 3 months and microscopy. Immune responses were evaluated by ELISA antibody titer, CD4, CD8 T cell populations and survival post challenge by P. multocida in mice.Results: The separation of aqueous and oil phase of emulsion by centrifugation and storage test were 0 and 6.76% in A-OAV as compared to 11.00 and 26.39% in OAV, respectively. The mean droplet size was significantly smaller (p<0.01 in A–OAV as compared to OAV. The A–OAV recorded higher ELISA antibody titer (p<0.05 up to 21st days post vaccination, and higher CD4 (p>0.05 and CD8 T cell (p<0.05 populations compared to OAV. The A–OAV group conferred 100% protection after challenge with both 100 LD50 and 1000 LD50 as compared to 100 and 60% respective protection by OAV group.Conclusion: The results indicates that A–OAV had better emulsion stability, produces higher level of CD4, CD8 T cells and antibody titer with better protection compared to oil adjuvant vaccine.

  9. Effect of adjuvant nasal continuous positive airway pressure therapy on immune response and organ injury in children with severe pneumonia

    Institute of Scientific and Technical Information of China (English)

    Ni-Na Huang; Yu-Dan Zhang

    2016-01-01

    Objective:To analyze the effect of adjuvant nasal continuous positive airway pressure therapy on immune response and organ injury in children with severe pneumonia.Methods:A total of 90 children with severe pneumonia were randomly divided into observation group and control group (n=45), control group received conventional therapy, observation group accepted regular + adjuvant nasal continuous positive airway pressure therapy, and then differences in immune globulin, Th1/Th2 indexes, blood coagulation indexes, echocardiography parameters and so on were compared between two groups of children.Results:IgG2, IgG3, IgA and IgM content in peripheral blood of observation group were higher than those of control group; Th1/Th2 indexes IL-4 and IFN-γ content in serum as well as IL-4/IFN-γ level were lower than those of control group; blood coagulation indexes PT, TT, APTT and D-D levels were lower than those of control group while FIB and PLT levels were higher than those of control group; echocardiography parameters PVAT and AVAT levels were higher than those of control group while PFVMA level was lower than that of control group.Conclusions: Adjuvant nasal continuous positive airway pressure therapy helps to enhance the immune response and optimize blood coagulation function and cardiac function in children with severe pneumonia.

  10. Effect of adjuvant lactulose enema therapy on outcome and intestinal mucosal barrier function in patients with acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Ling Gao; Ming-Quan Li

    2016-01-01

    Objective:To analyze the effect of adjuvant lactulose enema therapy on outcome and intestinal mucosal barrier function in patients with acute pancreatitis.Methods: A total of 98 patients with acute pancreatitis were randomly divided into observation group and control group, control group received conventional symptomatic treatment, observation group received symptomatic treatment + adjuvant lactulose enema therapy, and differences in levels of inflammatory cytokines, RAAS system-related molecules and mucosal barrier function-related indexes in serum as well as intestinal flora quantity in stool samples were compared between two groups after treatment.Results:Serum inflammatory cytokines IL-1β, IL-6, IL-8, PCT and TNF-α levels of enema group were significantly lower than those of control group; serum RAAS system molecules R, AngI, AngII and ALD levels were significantly lower than those of control group; serum mucosal barrier function indexes D-lactate, LPS, I-FABP and DAO levels were significantly lower than those of control group; the quantity of bifidobacterium and lactobacillus in stool samples were significantly more than those of control group while the quantity of enterobacterium, enterococcus and E. coli were significantly lower than those of control group.Conclusion:Adjuvant lactulose enema therapy can promote the improvement of acute pancreatitis, and restore patients’ intestinal mucosal barrier function.

  11. Effect of Zinc gluconate adjuvant therapy on myocardial damage, immunologic function and serum inflammatory factors in children with rotaviral enteritis

    Institute of Scientific and Technical Information of China (English)

    Jun Zhu

    2015-01-01

    Objective:To analyze the effects of Zinc gluconate adjuvant therapy on Rotavirus myocardial injury, immune function and serum inflammatory factors of children with viral enteritis. Methods:A total of 138 Rotavirus viral enteritis children were enrolled as research objects. According to stochastic indicator method, they were divided into control group (n=69 cases) which received clinical routine treatment, and observation group (n=69 cases) which received Zinc gluconate adjuvant therapy, myocardial enzyme spectrum; serum inflammatory cytokines and immune function of the two groups were compared.Results:(1) LDH, CK, CK-MB, cTnⅠ myocardial enzyme indexes of the observation group were significantly lower than that of the control group (P<0.05). (2) serum zinc gluconate auxiliary CD19+CD5+CD1dhi B cells expression level of the observation group were higher than that of the control group, CD11b and CD40-CD40L stimulus molecule expression levels of the observation group were significantly lower than that of the control group (P<0.05). (3) Serum zinc gluconate auxiliary TRF1, TRF2 expression levels of the observation group were significantly higher than that of the control group but IL-12 level was lower than control group (P<0.05).Conclusion:Zinc gluconate adjuvant therapy could help to avoid the heart of the children with rotavirus virus enteritis loss, enhance immune function,reduce level of systemic inflammation.

  12. Toxicity during l-LV/5FU adjuvant chemotherapy as a modified RPMI regimen for patients with colorectal cancer.

    Science.gov (United States)

    Hotta, Tsukasa; Takifuji, Katsunari; Arii, Kazuo; Yokoyama, Shozo; Matsuda, Kenji; Higashiguchi, Takashi; Tominaga, Toshiji; Oku, Yoshimasa; Yamaue, Hiroki

    2005-08-01

    l-leucovorin (LV)/5-fluorouracil (5FU) may play an important role, as an adjuvant chemotherapy, in improving the survival of patients with stage III colorectal cancer. However, severe toxicity of the chemotherapeutic agent could be fatal. Adverse effects, including bone marrow suppression, liver damage, renal damage, and glucose tolerance, were evaluated daily during 3 courses of l-LV/5FU-modified RPMI regimen adjuvant chemotherapy for 22 patients with stage III colorectal cancer. Decrease in the serum levels of neutrophils and platelets occurred in the 1st course, which became more obvious after three or four administrations of l-LV/5FU in the 1st course. Furthermore, serum levels of leukocytes, neutrophils, and platelets on the re-start day of this chemotherapy after 2-week intervals were lower than those on the start day of this chemotherapy. In the evaluation of liver damage, renal damage, and glucose tolerance; serum alanine aminotransferase level in the 2nd course, serum total bilirubin (T.Bil) level in the 1st course, and serum creatinine level in the 1st course deteriorated during the course. T.Bil levels on the re-start day of this chemotherapy after 2-week intervals were especially high compared to that on the start day. The more courses of this chemotherapy we perform, the more attention we must pay to bone marrow suppression and hyperbilirubinemia. Thus, we clarified the attentive point of side effect of l-LV/5FU adjuvant chemotherapy for colorectal cancer.

  13. Adjuvant 5FU plus levamisole in colonic or rectal cancer: improved survival in stage II and III.

    Science.gov (United States)

    Taal, B G; Van Tinteren, H; Zoetmulder, F A

    2001-11-16

    Based on the first favourable results of adjuvant therapy of 5FU plus levamisole in Dukes C colonic cancer in 1990, we conducted a prospective trial. 1029 patients were randomised to receive one year 5FU plus levamisole or no further treatment following curative surgery for stage II or III colon (n = 730) or rectal cancer (n = 299). 45% were in stage II and 55% in stage III. With a median follow-up of 4 years and 9 months a significant reduction in odds of death (25%, SD 9%, P = 0.007) was observed for those with adjuvant treatment (65% at 5 year) compared to the observation group (55%). Improved relative survival was present in stage III (56% vs 44%), and in stage II patients (78% vs 70%). In rectal cancer a non-significant difference in disease-free or overall survival was observed. Distant metastases developed in 76%, while local recurrence alone occurred in 14%. An early start of adjuvant treatment (5FU plus levamisole was 69%. Severe toxicity did not occur. In conclusion, one year 5FU plus levamisole was of benefit in stage II and III colonic cancer; in rectal cancer a significant positive effect could not be demonstrated.

  14. Cholera toxin B subunit acts as a potent systemic adjuvant for HIV-1 DNA vaccination intramuscularly in mice.

    Science.gov (United States)

    Hou, Jue; Liu, Ying; Hsi, Jenny; Wang, Hongzhi; Tao, Ran; Shao, Yiming

    2014-01-01

    Cholera toxin B subunit (CTB) was investigated as a classical mucosal adjuvant that can increase vaccine immunogenicity. In this study, we found out the in vitro efficacy of cholera toxin B subunit (CTB) in activating mice bone marrow-derived dendritic cells (BMDCs) through Toll-like receptor signaling pathways. In vitro RNA and transcriptional level profiling arrays revealed that CTB guides high levels of Th1 and Th2 type cytokines, inflammatory cytokines, and chemokines. Based on the robustness of these profiling results, we examined the induction of HIV Env-specific immunity by CTB co-inoculated with HIV Env DNA vaccine intramuscularly in vivo. CTB enhanced HIV-Env specific cellular immune responses in Env-specific IFN-γ ELISPOT, compared with DNA vaccine alone. Moreover, CTB induced high levels of Env specific humoral response and promoted antibody maturation after the third round of vaccination. This combination immunization strategy induced a Th2-type bias response which is indicative of a high ratio of IgG1/IgG2a. This study reports that CTB as a classical mucosal adjuvant could enhance HIV-1 DNA-based vaccine immunogenicity intramuscularly; therefore, these findings suggest that CTB could serve as an effective candidate adjuvant for DNA vaccination.

  15. Green propolis phenolic compounds act as vaccine adjuvants, improving humoral and cellular responses in mice inoculated with inactivated vaccines

    Directory of Open Access Journals (Sweden)

    Geferson Fischer

    2010-11-01

    Full Text Available Adjuvants play an important role in vaccine formulations by increasing their immunogenicity. In this study, the phenolic compound-rich J fraction (JFR of a Brazilian green propolis methanolic extract stimulated cellular and humoral immune responses when co-administered with an inactivated vaccine against swine herpesvirus type 1 (SuHV-1. When compared to control vaccines that used aluminium hydroxide as an adjuvant, the use of 10 mg/dose of JFR significantly increased (p < 0.05 neutralizing antibody titres against SuHV-1, as well as the percentage of protected animals following SuHV-1 challenge (p < 0.01. Furthermore, addition of phenolic compounds potentiated the performance of the control vaccine, leading to increased cellular and humoral immune responses and enhanced protection of animals after SuHV-1 challenge (p < 0.05. Prenylated compounds such as Artepillin C that are found in large quantities in JFR are likely to be the substances that are responsible for the adjuvant activity.

  16. Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis.

    Science.gov (United States)

    Ives, Natalie J; Suciu, Stefan; Eggermont, Alexander M M; Kirkwood, John; Lorigan, Paul; Markovic, Svetomir N; Garbe, Claus; Wheatley, Keith

    2017-09-01

    Many randomised trials assessing interferon-α (IFN-α) as adjuvant therapy for high-risk malignant melanoma have been undertaken. To better assess the role of IFN-α, an individual patient data (IPD) meta-analysis of these trials was undertaken. IPD was sought from all randomised trials of adjuvant IFN-α versus no IFN-α for high-risk melanoma. Primary outcomes were event-free survival (EFS) and overall survival (OS). Standard methods for quantitative IPD meta-analysis were used. Subgroup analyses by dose, duration of treatment and various patient and disease-specific parameters were performed. Fifteen trials were included in the analysis (eleven with IPD). EFS was significantly improved with IFN-α (hazard ratio [HR] = 0.86, CI 0.81-0.91; P analysis provides clear evidence that adjuvant IFN-α significantly reduces the risk of relapse and improves survival and shows no benefit for higher doses compared to lower doses. The increased benefit in patients with ulcerated tumours, and lack of benefit in patients without ulceration, needs further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Anti-inflammation and anti-oxygen free radical effect of adjuvant Danshen injection treatment on viral myocarditis

    Institute of Scientific and Technical Information of China (English)

    Wen-Bao Liang; Jian Chen

    2016-01-01

    Objective:To analyze the anti-inflammation and anti-oxygen free radical effect of adjuvant Danshen injection treatment on viral myocarditis.Methods: A total of 90 children with viral myocarditis treated in our hospital from January 2014 to January 2016 were included in the research and randomly divided into observation group (n=45) and control group (n=45) according to the different treatment. Control group received clinical routine therapy for viral myocarditis, observation group received adjuvant Danshen injection treatment, and then levels of IL23/IL-17 inflammatory axis as well as cytokines, oxidation and anti-oxidation indexes, myocardial enzyme and illness-related proteins were compared between two groups.Results:Serum IL-17, IL-23, IL-1β, IL-6 and TNF-α values of observation group were lower than those of control group (P<0.05); serum MDA, AOPP and NO values of observation group after treatment were lower than those of control group while SOD and T-AOC values were higher than those of control group (P<0.05); serum cTnT, CK-MB, MCP-1 and H-FABP values of observation group after treatment were lower than those of control group (P<0.05). Conclusions:Adjuvant Danshen injection treatment for children with viral myocarditis can exert positive anti-inflammation and anti-oxygen free radical function, and it plays a positive role in myocardial protection.

  18. Establishment of a new quality control and vaccine safety test for influenza vaccines and adjuvants using gene expression profiling.

    Science.gov (United States)

    Momose, Haruka; Mizukami, Takuo; Kuramitsu, Madoka; Takizawa, Kazuya; Masumi, Atsuko; Araki, Kumiko; Furuhata, Keiko; Yamaguchi, Kazunari; Hamaguchi, Isao

    2015-01-01

    We have previously identified 17 biomarker genes which were upregulated by whole virion influenza vaccines, and reported that gene expression profiles of these biomarker genes had a good correlation with conventional animal safety tests checking body weight and leukocyte counts. In this study, we have shown that conventional animal tests showed varied and no dose-dependent results in serially diluted bulk materials of influenza HA vaccines. In contrast, dose dependency was clearly shown in the expression profiles of biomarker genes, demonstrating higher sensitivity of gene expression analysis than the current animal safety tests of influenza vaccines. The introduction of branched DNA based-concurrent expression analysis could simplify the complexity of multiple gene expression approach, and could shorten the test period from 7 days to 3 days. Furthermore, upregulation of 10 genes, Zbp1, Mx2, Irf7, Lgals9, Ifi47, Tapbp, Timp1, Trafd1, Psmb9, and Tap2, was seen upon virosomal-adjuvanted vaccine treatment, indicating that these biomarkers could be useful for the safety control of virosomal-adjuvanted vaccines. In summary, profiling biomarker gene expression could be a useful, rapid, and highly sensitive method of animal safety testing compared with conventional methods, and could be used to evaluate the safety of various types of influenza vaccines, including adjuvanted vaccine.

  19. Characterization of a novel oil-in-water emulsion adjuvant for swine influenza virus and Mycoplasma hyopneumoniae vaccines.

    Science.gov (United States)

    Galliher-Beckley, A; Pappan, L K; Madera, Rachel; Burakova, Y; Waters, A; Nickles, M; Li, X; Nietfeld, J; Schlup, J R; Zhong, Q; McVey, S; Dritz, S S; Shi, J

    2015-06-01

    Vaccines consisting of subunit or inactivated bacteria/virus and potent adjuvants are widely used to control and prevent infectious diseases. Because inactivated and subunit antigens are often less antigenic than live microbes, a growing need exists for the development of new and improved vaccine adjuvants that can elicit rapid and long-lasting immunity. Here we describe the development and characterization of a novel oil-in-water emulsion, OW-14. OW-14 contains low-cost plant-based emulsifiers and was added to antigen at a ratio of 1:3 with simple hand mixing. OW-14 was stable for prolonged periods of time at temperatures ranging from 4 to 40°C and could be sterilized by autoclaving. Our results showed that OW-14 adjuvanted inactivated swine influenza viruses (SIV; H3N2 and H1N1) and Mycoplasma hyopneumoniae (M. hyo) vaccines could be safely administered to piglets in two doses, three weeks apart. Injection sites were monitored and no adverse reactions were observed. Vaccinated pigs developed high and prolonged antibody titers to both SIV and M. hyo. Interestingly, antibody titers were either comparable or greater than those produced by commercially available FluSure (SIV) or RespiSure (M. hyo) vaccines. We also found that OW-14 can induce high antibody responses in pigs that were vaccinated with a decreased antigen dose. This study provides direct evidence that we have developed an easy-to-use and low-cost emulsion that can act as a powerful adjuvant in two common types of swine vaccines.

  20. Neo-adjuvant chemotherapy with cisplatin and short infusional 5-FU in advanced head and neck malignancies

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    Aich Ranen Kanti

    2005-01-01

    Full Text Available Background: Combination of radical surgery and radiotherapy is the standard management of head and neck malignancies. But due to considerable morbidity of surgery and associated cosmetic and functional deficiencies, often aggravated by adjuvant radiotherapy, many patients prefer only radiotherapy with its′ decreased chance of survival. Proper surgical facilities are also not accessible to most of our patients. Neo-adjuvant chemotherapy and loco-regional management by surgery and / or radiotherapy have emerged as a viable alternative. Aims: The purpose of this study is to find out the survival outcome as well as toxicity profile of Neo-adjuvant chemotherapy with cisplatin and short infusional (3 hours 5-FU followed by radiotherapy in advanced head and neck malignancies. Materials and Methods: From June 2002 to December 2003, seventy four patients with advanced head and neck malignancies were planned to be treated with Cisplatin (50 mg / sq. meter on Days 1 and 2 and 5 - FU (600 mg / sq. meter on Days 1, 2 and 3 by 3 hour infusion on Day care basis. On completion of four cycles of chemotherapy at 21 days interval, all patients were destined to receive 6000 cGy of radiotherapy to the loco - regional site. Results: At one year follow up on completion of therapy, 57% patients were alive and 31% patients were disease free. These 31% patients enjoyed a good quality of life in terms of cosmetic and functional deficits. Toxicities were moderate and easily manageable. Conclusion: The study indicated that neo-adjuvant chemotherapy with Cisplatin and short infusional 5 - FU may be delivered on day care basis and results are comparable with Cisplatin and 96 hours continuous infusional 5 - FU. Thus avoiding the continuous infusional 5 - FU, 7 to 10 days in-patient hospitalization during each cycle may be avoided which is a constrain in developing countries like us.

  1. Efficacy of Adjuvant 5-Fluorouracil Therapy for Patients with EMAST-Positive Stage II/III Colorectal Cancer.

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    Yasushi Hamaya

    Full Text Available Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST is a genetic signature found in up to 60% of colorectal cancers (CRCs that is caused by somatic dysfunction of the DNA mismatch repair (MMR protein hMSH3. We have previously shown in vitro that recognition of 5-fluorouracil (5-FU within DNA and subsequent cytotoxicity was most effective when both hMutSα (hMSH2-hMSH6 heterodimer and hMutSβ (hMSH2-hMSH3 heterodimer MMR complexes were present, compared to hMutSα > hMutSβ alone. We tested if patients with EMAST CRCs (hMutSβ defective had diminished response to adjuvant 5-FU chemotherapy, paralleling in vitro findings. We analyzed 230 patients with stage II/III sporadic colorectal cancers for which we had 5-FU treatment and survival data. Archival DNA was analyzed for EMAST (>2 of 5 markers mutated among UT5037, D8S321, D9S242, D20S82, D20S85 tetranucleotide loci. Kaplan-Meier survival curves were generated and multivariate analysis was used to determine contribution to risk. We identified 102 (44% EMAST cancers. Ninety-four patients (41% received adjuvant 5-FU chemotherapy, and median follow-up for all patients was 51 months. Patients with EMAST CRCs demonstrated improved survival with adjuvant 5FU to the same extent as patients with non-EMAST CRCs (P<0.05. We observed no difference in survival between patients with stage II/III EMAST and non-EMAST cancers (P = 0.36. There is improved survival for stage II/III CRC patients after adjuvant 5-FU-based chemotherapy regardless of EMAST status. The loss of contribution of hMSH3 for 5-FU cytotoxicity may not adversely affect patient outcome, contrasting patients whose tumors completely lack DNA MMR function (MSI-H.

  2. Efficacy of Adjuvant 5-Fluorouracil Therapy for Patients with EMAST-Positive Stage II/III Colorectal Cancer

    Science.gov (United States)

    Hamaya, Yasushi; Guarinos, Carla; Tseng-Rogenski, Stephanie S.; Iwaizumi, Moriya; Das, Ritabrata; Jover, Rodrigo; Castells, Antoni; Llor, Xavier; Andreu, Montserrat; Carethers, John M.

    2015-01-01

    Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST) is a genetic signature found in up to 60% of colorectal cancers (CRCs) that is caused by somatic dysfunction of the DNA mismatch repair (MMR) protein hMSH3. We have previously shown in vitro that recognition of 5-fluorouracil (5-FU) within DNA and subsequent cytotoxicity was most effective when both hMutSα (hMSH2-hMSH6 heterodimer) and hMutSβ (hMSH2-hMSH3 heterodimer) MMR complexes were present, compared to hMutSα > hMutSβ alone. We tested if patients with EMAST CRCs (hMutSβ defective) had diminished response to adjuvant 5-FU chemotherapy, paralleling in vitro findings. We analyzed 230 patients with stage II/III sporadic colorectal cancers for which we had 5-FU treatment and survival data. Archival DNA was analyzed for EMAST (>2 of 5 markers mutated among UT5037, D8S321, D9S242, D20S82, D20S85 tetranucleotide loci). Kaplan-Meier survival curves were generated and multivariate analysis was used to determine contribution to risk. We identified 102 (44%) EMAST cancers. Ninety-four patients (41%) received adjuvant 5-FU chemotherapy, and median follow-up for all patients was 51 months. Patients with EMAST CRCs demonstrated improved survival with adjuvant 5FU to the same extent as patients with non-EMAST CRCs (P<0.05). We observed no difference in survival between patients with stage II/III EMAST and non-EMAST cancers (P = 0.36). There is improved survival for stage II/III CRC patients after adjuvant 5-FU-based chemotherapy regardless of EMAST status. The loss of contribution of hMSH3 for 5-FU cytotoxicity may not adversely affect patient outcome, contrasting patients whose tumors completely lack DNA MMR function (MSI-H). PMID:25996601

  3. Clinical impact of PET/CT imaging after adjuvant therapy in patients with oral cavity squamous cell carcinoma.

    Science.gov (United States)

    Lin, Huan-Chun; Kang, Chung-Jan; Huang, Shiang-Fu; Wang, Hung-Ming; Lin, Chien-Yu; Lee, Li-Yu; Liao, Chun-Ta; Yen, Tzu-Chen

    2017-09-01

    This single-center retrospective study of prospectively collected data was aimed at comparing the clinical outcomes of positron emission tomography/computed tomography (PET/CT) for patients with oral cavity squamous cell carcinoma (OSCC) with symptomatic recurrences identified by PET/CT imaging following adjuvant therapy (Group A) versus those of cases with asymptomatic recurrences diagnosed through periodic post-adjuvant therapy PET/CT surveillance (Group B). We also sought to establish the priority of salvage therapy in the two study groups. We identified 111 patients with advanced resected OSCC who developed recurrences following adjuvant therapy (51 in Group A and 60 in Group B). Histopathology served as the gold standard for recurrent lesions. The impact of post-adjuvant therapy PET/CT surveillance was examined with Kaplan-Meier curves and Cox proportional hazards regression models. The 2-year DSS and OS rates were marginally or significantly higher in Group B than in Group A (P = 0.073 and P = 0.025, respectively). Time-dependent ROC curve analysis demonstrated that the optimal cutoff values for time to positive PET/CT findings in relation to OS were 12 months for Group A and 9 months for Group B, respectively. Independent risk factors identified in multivariate analyses were used to devise two prognostic scoring systems for 2-year DSS and OS in each study group (all P PET/CT surveillance is a valuable tool for early detection of recurrent lesion(s) in asymptomatic OSCC patients who bear risk factors for disease recurrence. The presence of clinical symptoms and a short time to positive PET/CT findings were adverse prognostic factors for clinical outcome in patients with advanced OSCC. The priority of salvage therapy is discussed in each patient subgroup according to the devised prognostic scoring systems.

  4. Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles.

    Science.gov (United States)

    Tonkin, Daniel R; Whitmore, Alan; Johnston, Robert E; Barro, Mario

    2012-06-22

    Replicon particles derived from Venezuelan equine encephalitis virus (VEE) are infectious non-propagating particles which act as a safe and potent systemic, mucosal, and cellular adjuvant when delivered with antigen. VEE and VEE replicon particles (VRP) can target multiple cell types including dendritic cells (DCs). The role of these cell types in VRP adjuvant activity has not been previously evaluated, and for these studies we focused on the contribution of DCs to the response to VRP. By analysis of VRP targeting in the draining lymph node, we found that VRP induced rapid recruitment of TNF-secreting monocyte-derived inflammatory dendritic cells. VRP preferentially infected these inflammatory DCs as well as classical DCs and macrophages, with less efficient infection of other cell types. DC depletion suggested that the interaction of VRP with classical DCs was required for recruitment of inflammatory DCs, induction of high levels of many cytokines, and for stable transport of VRP to the draining lymph node. Additionally, in vitro-infected DCs enhanced antigen-specific responses by CD4 and CD8 T cells. By transfer of VRP-infected DCs into mice we showed that these DCs generated an inflammatory state in the draining lymph node similar to that achieved by VRP injection. Most importantly, VRP-infected DCs were sufficient to establish robust adjuvant activity in mice comparable to that produced by VRP injection. These findings indicate that VRP infect, recruit and activate both classical and inflammatory DCs, and those DCs become mediators of the VRP adjuvant activity. Published by Elsevier Ltd.

  5. Comparison of Intranasal Outer Membrane Vesicles with Cholera Toxin and Injected MF59C.1 as Adjuvants for Malaria Transmission Blocking Antigens AnAPN1 and Pfs48/45

    Directory of Open Access Journals (Sweden)

    Michael Pritsch

    2016-01-01

    Full Text Available Purified protein vaccines often require adjuvants for efficient stimulation of immune responses. There is no licensed mucosal adjuvant on the market to adequately boost the immune response to purified antigens for intranasal applications in humans. Bacterial outer membrane vesicles (OMV are attractive candidates potentially combining antigenic and adjuvant properties in one substance. To more precisely characterize the potential of Escherichia coli OMV for intranasal vaccination with heterologous antigens, immune responses for AnAPN1 and Pfs48/45 as well as ovalbumin as a reference antigen were assessed in mice. The intranasal adjuvant cholera toxin (CT and parenteral adjuvant MF59C.1 were used in comparison. Vaccinations were administered intranasally or subcutaneously. Antibodies (total IgG and IgM as well as subclasses IgG1, IgG2a, IgG2b, and IgG3 were measured by ELISA. T cell responses (cytotoxic T cells, Th1, Th17, and regulatory T cells were determined by flow cytometry. When OMV were used as adjuvant for intranasal immunization, antibody and cellular responses against all three antigens could be induced, comparable to cholera toxin and MF59C.1. Antigen-specific IgG titres above 1 : 105 could be detected in all groups. This study provides the rationale for further development of OMV as a vaccination strategy in malaria and other diseases.

  6. A Schistosoma japonicum chimeric protein with a novel adjuvant induced a polarized Th1 immune response and protection against liver egg burdens

    Directory of Open Access Journals (Sweden)

    Xue Xiangyang

    2009-05-01

    Full Text Available Abstract Background Schitosomiasis japonica is still a significant public health problem in China. A protective vaccine for human or animal use represents an important strategy for long-term control of this disease. Due to the complex life cycle of schistosomes, different vaccine design approaches may be necessary, including polyvalent subunit vaccines. In this study, we constructed four chimeric proteins (designated SjGP-1~4 via fusion of Sj26GST and four individual paramyosin fragments. We tested these four proteins as vaccine candidates, and investigated the effect of deviating immune response on protection roles in mice. Methods The immunogencity and protection efficacy of chimeric proteins were evaluated in mice. Next, the chimeric protein SjGP-3 was selected and formulated in various adjuvants, including CFA, ISA 206, IMS 1312 and ISA 70M. The titers of antigen-specific IgG, IgE and IgG subclass were measured. The effect of adjuvant on cytokine production and percentages of CD3+CD8-IFN-γ+ cells and CD3+CD8-IL-4+ cells were analyzed at different time points. Worm burdens and liver egg counts in different adjuvant groups were counted to evaluate the protection efficacy against cercarial challenge. Results Immunization of mice with chimeric proteins provided various levels of protection. Among the four proteins, SjGP-3 induced the highest level of protection, and showed enhanced protective efficacy compared with its individual component Sj26GST. Because of this, SjGP-3 was further formulated in various adjuvants to investigate the effect of adjuvant on immune deviation. The results revealed that SjGP-3 formulated in veterinary adjuvant ISA 70M induced a lasting polarized Th1 immune response, whereas the other adjuvants, including CFA, ISA 206 and IMS 1312, generated a moderate mixed Th1/Th2 response after immunization but all except for IMS 1312 shifted to Th2 response after onset of eggs. More importantly, the SjGP-3/70M formulation induced

  7. Glucopyranosyl Lipid Adjuvant (GLA), a Synthetic TLR4 agonist, promotes potent systemic and mucosal responses to intranasal immunization with HIVgp140.

    Science.gov (United States)

    Arias, Mauricio A; Van Roey, Griet A; Tregoning, John S; Moutaftsi, Magdalini; Coler, Rhea N; Windish, Hillarie P; Reed, Steven G; Carter, Darrick; Shattock, Robin J

    2012-01-01

    Successful vaccine development against HIV will likely require the induction of strong, long-lasting humoral and cellular immune responses in both the systemic and mucosal compartments. Based on the known immunological linkage between the upper-respiratory and urogenital tracts, we explored the potential of nasal adjuvants to boost immunization for the induction of vaginal and systemic immune responses to gp140. Mice were immunized intranasally with HIV gp140 together with micellar and emulsion formulations of a synthetic TLR4 agonist, Glucopyranosyl Lipid Adjuvant (GLA) and responses were compared to R848, a TLR7/8 agonist, or chitosan, a non TLR adjuvant. GLA and chitosan but not R848 greatly enhanced serum immunoglobulin levels when compared to antigen alone. Both GLA and chitosan induced high IgG and IgA titers in nasal and vaginal lavage and feces. The high IgA and IgG titers in vaginal lavage were associated with high numbers of gp140-specific antibody secreting cells in the genital tract. Whilst both GLA and chitosan induced T cell responses to immunization, GLA induced a stronger Th17 response and chitosan induced a more Th2 skewed response. Our results show that GLA is a highly potent intranasal adjuvant greatly enhancing humoral and cellular immune responses, both systemically and mucosally.

  8. Glucopyranosyl Lipid Adjuvant (GLA, a Synthetic TLR4 agonist, promotes potent systemic and mucosal responses to intranasal immunization with HIVgp140.

    Directory of Open Access Journals (Sweden)

    Mauricio A Arias

    Full Text Available Successful vaccine development against HIV will likely require the induction of strong, long-lasting humoral and cellular immune responses in both the systemic and mucosal compartments. Based on the known immunological linkage between the upper-respiratory and urogenital tracts, we explored the potential of nasal adjuvants to boost immunization for the induction of vaginal and systemic immune responses to gp140. Mice were immunized intranasally with HIV gp140 together with micellar and emulsion formulations of a synthetic TLR4 agonist, Glucopyranosyl Lipid Adjuvant (GLA and responses were compared to R848, a TLR7/8 agonist, or chitosan, a non TLR adjuvant. GLA and chitosan but not R848 greatly enhanced serum immunoglobulin levels when compared to antigen alone. Both GLA and chitosan induced high IgG and IgA titers in nasal and vaginal lavage and feces. The high IgA and IgG titers in vaginal lavage were associated with high numbers of gp140-specific antibody secreting cells in the genital tract. Whilst both GLA and chitosan induced T cell responses to immunization, GLA induced a stronger Th17 response and chitosan induced a more Th2 skewed response. Our results show that GLA is a highly potent intranasal adjuvant greatly enhancing humoral and cellular immune responses, both systemically and mucosally.

  9. Testing a Protocol for a Randomized Controlled Trial of Therapeutic versus Placebo Shoulder Strapping as an Adjuvant Intervention Early after Stroke.

    Science.gov (United States)

    Appel, Caroline; Perry, Lin; Jones, Fiona

    2015-06-01

    This study tested a protocol for a randomized controlled trial of therapeutic versus placebo shoulder strapping as an adjuvant intervention early after stroke. Despite widespread use, there is little evidence of the efficacy or acceptability of shoulder strapping to improve arm function in patients with shoulder paresis following stroke. This study tested a protocol designed to trial shoulder strapping as an adjuvant therapy in patients with shoulder paresis after stroke and tested its acceptability for patients and clinical staff. A multiple-method design comprised one quantitative randomized, double-blind, placebo-controlled study and two qualitative exploratory investigations entailing patient interviews and staff surveys. Seventeen sub-acute stroke patients with shoulder paresis were recruited in London stroke service settings between November 2007 and December 2009. Outcomes from a 4-week therapeutic strapping protocol were compared with those of placebo strapping as an adjunct to conventional rehabilitation. Minimal adverse events and greater improvement in arm function (Action Research Arm Test) were seen with therapeutic compared with placebo strapping (effect size 0.34). Patients and staff found the strapping acceptable with minimal adverse effects. This study provided data for sample size calculation and demonstrated a workable research protocol to investigate the efficacy of shoulder strapping as an adjuvant intervention to routine rehabilitation for stroke patients. Small-scale findings continue to flag the importance of investigating this topic. The protocol is recommended for a definitive trial of shoulder strapping as an adjuvant intervention.

  10. Adjuvant Activity of a Novel Metabolizable Lipid Emulsion with Inactivated Viral Vaccines

    Science.gov (United States)

    1980-06-01

    hamsters, sheep, and two species of nonhuman 0 primates which demonstrate the adjuvant activity of a new metabolizable lipid emulsion with marginally...mice, hamsters, sheep, and two species of nonhuman primates . This adjuvant has several 10.000 advantages over other known adjuvant com-cpounds. It is...plaque neutralization method for arboviruses . Proc. Soc. granulomatous reaction was not observed. We Exp. Biol. Med. 125:741-747. closely observed the

  11. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations

    OpenAIRE

    2016-01-01

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al3+ in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, pote...

  12. Adjuvant postoperative radiochemotherapy for patients with gastric carcinoma: a single institution experience

    Institute of Scientific and Technical Information of China (English)

    Manal El-Baradie; Ola Khorshid; Ahmed Touny

    2012-01-01

    months, were 61.2%, 66.7% and 71%, respectively. At 3 and 5 years the corresponding values were: OS (42% and 28%), LRC (64% and 50.4%) and MFS (56.3% and 49%), respectively. Only stage and degree of nodal involvement had an adverse effect on all survival rates. Proximal lesion had poor OS rates. As regard LR control rate, mucinous cell type, and high grade had a bad effect. Although patients with less than D1 dissection had low OS and LRC rate, it didn't reach significant level. There was a significant improved 5-year OS rate for concurrent chemoradiotherapy (CCRTh, 55%) versus no or single adjuvant modality (27%), P = 0.035. A subgroup analysis according to CTH regimen showed a trend for all survival rates with ECF compared to bolus 5FU/LV. However, none was statistically significant. Conclusion: In oper-able gastric carcinoma, postoperative concomitant radiochemotherapy with 5FU and LV is feasible with acceptable toxicity with a significant increase of locoregional control. A well designed phase III clinical trial – with ECF regimen and conformal radiotherapy – is worth to start to increase local control and decrease toxicity.

  13. Adjuvants and delivery systems in veterinary vaccinology: current state and future developments

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Dedieu, Laurence; Johnson, Nicholas;

    2011-01-01

    low immunogenicity themselves. The development of such adjuvants may take advantage of the increased knowledge of the molecular mechanisms and factors controlling these responses. However, knowledge of such molecular details of immune mechanisms is relatively scarce for species other than humans......Modern adjuvants should induce strong and balanced immune responses, and it is often desirable to induce specific types of immunity. As an example, efficient Th1-immunity-inducing adjuvants are highly in demand. Such adjuvants promote good cell-mediated immunity against subunit vaccines that have...

  14. Review on adjuvant chemotherapy for rectal cancer - why do treatment guidelines differ so much?

    Science.gov (United States)

    Poulsen, Laurids Ø; Qvortrup, Camilla; Pfeiffer, Per; Yilmaz, Mette; Falkmer, Ursula; Sorbye, Halfdan

    2015-04-01

    The use of postoperative adjuvant chemotherapy is controversial for rectal adenocarcinoma. Both international and national guidelines display a great span varying from recommending no adjuvant chemotherapy at all, over single drug 5-fluororuacil (5-FU), to combinations of 5-FU/oxaliplatin. A review of the literature was made identifying 24 randomized controlled trials on adjuvant treatment of rectal cancer based on about 10 000 patients. The trials were subdivided into a number of clinically relevant subgroups. As regards patients treated with preoperative (chemo) radiotherapy, four randomized studies were found where use of adjuvant chemotherapy showed no benefit in survival. Three trials were found in which a subset of patients received preoperative (chemo) radiotherapy. Two of these trials showed a statistically significant benefit of adjuvant chemotherapy. Twenty trials were identified in which the patients did not receive preoperative (chemo) radiotherapy, including five Asian studies in which a statistically significant benefit from adjuvant chemotherapy was reported. Most of the data found did not support the use of postoperative adjuvant chemotherapy for patients already treated with preoperative (chemo) radiotherapy. For patients not treated preoperatively, several studies support the use of single agent 5-FU chemotherapy. Treatment guidelines seem to differ according to if preoperative chemoradiation is considered of importance for use of adjuvant chemotherapy and if adjuvant colon cancer studies are considered transferrable to rectal cancer patients regardless of the molecular differences.

  15. The Impact of Adjuvant Radiation Therapy for High-Grade Gliomas by Histology in the United States Population

    Energy Technology Data Exchange (ETDEWEB)

    Rusthoven, Chad G., E-mail: Chad.Rusthoven@ucdenver.edu [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Carlson, Julie A.; Waxweiler, Timothy V. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Dally, Miranda J.; Barón, Anna E. [Department of Biostatistics and Informatics, University of Colorado School of Medicine, Aurora, Colorado (United States); Yeh, Norman; Gaspar, Laurie E.; Liu, Arthur K. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Ney, Douglas E.; Damek, Denise M. [Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado (United States); Lillehei, Kevin O. [Department of Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado (United States); Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States)

    2014-11-15

    Purpose: To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. Results: The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overall survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were

  16. Remifentanil-based total intravenous anesthesia for pediatric rigid bronchoscopy: comparison of adjuvant propofol and ketamine

    Directory of Open Access Journals (Sweden)

    Mefkur Bakan

    2014-06-01

    Full Text Available OBJECTIVE:Laryngoscopy and stimuli inside the trachea cause an intense sympatho-adrenal response. Remifentanil seems to be the optimal opioid for rigid bronchoscopy due to its potent and short-acting properties. The purpose of this study was to compare bolus propofol and ketamine as an adjuvant to remifentanil-based total intravenous anesthesia for pediatric rigid bronchoscopy.MATERIALS AND METHODS:Forty children under 12 years of age who had been scheduled for a rigid bronchoscopy were included in this study. After midazolam premedication, a 1 µg/kg/min remifentanil infusion was started, and patients were randomly allocated to receive either propofol (Group P or ketamine (Group K as well as mivacurium for muscle relaxation. Anesthesia was maintained with a 1 µg/kg/min remifentanil infusion and bolus doses of propofol or ketamine. After the rigid bronchoscopy, 0.05 µg/kg/min of remifentanil was maintained until extubation. Hemodynamic parameters, emergence characteristics, and adverse events were evaluated.RESULTS:The demographic variables were comparable between the two groups. The decrease in mean arterial pressure from baseline values to the lowest values during rigid bronchoscopy was greater in Group P (p= 0.049, while the reduction in the other parameters and the incidence of adverse events were comparable between the two groups. The need for assisted or controlled mask ventilation after extubation was higher in Group K.CONCLUSION:Remifentanil-based total intravenous anesthesia with propofol or ketamine as an adjuvant drug along with controlled ventilation is a viable technique for pediatric rigid bronchoscopy. Ketamine does not provide a definite advantage over propofol with respect to hemodynamic stability during rigid bronchoscopy, while propofol seems more suitable during the recovery period.

  17. Remifentanil-based total intravenous anesthesia for pediatric rigid bronchoscopy: comparison of adjuvant propofol and ketamine.

    Science.gov (United States)

    Bakan, Mefkur; Topuz, Ufuk; Umutoglu, Tarik; Gundogdu, Gokhan; Ilce, Zekeriya; Elicevik, Mehmet; Kaya, Guner

    2014-06-01

    Laryngoscopy and stimuli inside the trachea cause an intense sympatho-adrenal response. Remifentanil seems to be the optimal opioid for rigid bronchoscopy due to its potent and short-acting properties. The purpose of this study was to compare bolus propofol and ketamine as an adjuvant to remifentanil-based total intravenous anesthesia for pediatric rigid bronchoscopy. Forty children under 12 years of age who had been scheduled for a rigid bronchoscopy were included in this study. After midazolam premedication, a 1 µg/kg/min remifentanil infusion was started, and patients were randomly allocated to receive either propofol (Group P) or ketamine (Group K) as well as mivacurium for muscle relaxation. Anesthesia was maintained with a 1 µg/kg/min remifentanil infusion and bolus doses of propofol or ketamine. After the rigid bronchoscopy, 0.05 µg/kg/min of remifentanil was maintained until extubation. Hemodynamic parameters, emergence characteristics, and adverse events were evaluated. The demographic variables were comparable between the two groups. The decrease in mean arterial pressure from baseline values to the lowest values during rigid bronchoscopy was greater in Group P (p = 0.049), while the reduction in the other parameters and the incidence of adverse events were comparable between the two groups. The need for assisted or controlled mask ventilation after extubation was higher in Group K. Remifentanil-based total intravenous anesthesia with propofol or ketamine as an adjuvant drug along with controlled ventilation is a viable technique for pediatric rigid bronchoscopy. Ketamine does not provide a definite advantage over propofol with respect to hemodynamic stability during rigid bronchoscopy, while propofol seems more suitable during the recovery period.

  18. Adjuvant radiotherapy for stage I endometrial cancer: an updated Cochrane systematic review and meta-analysis.

    Science.gov (United States)

    Kong, Anthony; Johnson, Nick; Kitchener, Henry C; Lawrie, Theresa A

    2012-11-07

    The role of adjuvant radiotherapy in stage I endometrial cancer has changed in recent years. This updated Cochrane systematic review aimed to reexamine the efficacy and toxicity of adjuvant radiotherapy vs no treatment in stage I endometrial cancer. We searched various databases including The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and the Specialised Register of the Cochrane Gynaecological Cancer Review Group (CGCRG) for randomized controlled trials that met the predefined inclusion criteria. The primary outcome was overall survival (OS); secondary outcomes were endometrial cancer-specific survival, locoregional recurrence, distant recurrence, and toxicity. Hazard ratios (HRs) were estimated and pooled if possible; otherwise, dichotomous data were extracted. All statistical tests were two-sided. Of the eight included trials, seven trials (3628 women) compared external beam radiotherapy (EBRT) and no EBRT (or vaginal brachytherapy [VBT]), and one trial (645 women) compared VBT and no additional treatment. EBRT statistically significantly reduced locoregional recurrence compared with no EBRT (or VBT alone) (HR = 0.36, 95% confidence Interval [CI] = 0.25 to 0.52; P endometrial cancer-specific survival (HR = 0.96, 95% CI = 0.72 to 1.28; P = .80), or distant recurrence rates (risk ratio = 1.04, 95% CI = 0.80 to 1.35; P = .77). EBRT was associated with an increased risk of severe acute toxicity, severe late toxicity, and reduced quality of life scores. EBRT reduces the risk of locoregional recurrence but has no statistically significant impact on cancer-related deaths or OS. However, EBRT is associated with clinically and statistically significant morbidity and a reduction in quality of life.

  19. Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice.

    Directory of Open Access Journals (Sweden)

    Ojas H Mehta

    Full Text Available Neisseria meningitidis lipopolysaccharide (LPS has adjuvant properties that can be exploited to assist vaccine immunogenicity. The modified penta-acylated LPS retains the adjuvant properties of hexa-acylated LPS but has a reduced toxicity profile. In this study we investigated whether two modified glycoform structures (LgtE and IcsB of detoxified penta-acylated LPS exhibited differential adjuvant properties when formulated as native outer membrane vesicles (nOMVs as compared to the previously described LgtB variant. Detoxified penta-acylated LPS was obtained by disruption of the lpxL1 gene (LpxL1 LPS, and three different glycoforms were obtained by disruption of the lgtB, lgtE or icsB genes respectively. Mice (mus musculus were immunized with a recombinant PorA P1.7-2,4 (rPorA protein co-administered with different nOMVs (containing a different PorA serosubtype P1.7,16, each of which expressed one of the three penta-acylated LPS glycoforms. All nOMVs induced IgG responses against the rPorA, but the nOMVs containing the penta-acylated LgtB-LpxL1 LPS glycoform induced significantly greater bactericidal activity compared to the other nOMVs or when the adjuvant was Alhydrogel. Compared to LgtE or IcsB LPS glycoforms, these data support the use of nOMVs containing detoxified, modified LgtB-LpxL1 LPS as a potential adjuvant for future meningococcal protein vaccines.

  20. Immune protection conferred by recombinant MRLC (myosin regulatory light chain) antigen in TiterMax Gold® adjuvant against experimental fasciolosis in rats.

    Science.gov (United States)

    Henker, Luan C; Schwertz, Claiton I; Lucca, Neuber J; Piva, Manoela M; Prior, Keila C; Baska, Piotr; Norbury, Luke; Januszkiewicz, Kamil; Dezen, Diogenes; Duarte, Marta M M F; Moresco, Rafael N; Bertagnolli da Rosa, Liana; Mendes, Ricardo E

    2017-01-23

    Protection against experimental fasciolosis in rats immunized with recombinant myosin regulatory light chain (MRLC) in TiterMax Gold® adjuvant was assessed. The experimental trial consisted of four groups of 15 animals; group 1 was unimmunized and infected, group 2 was immunized with MRLC in adjuvant and infected, group 3 was infected and immunized with adjuvant only and group 4 was unimmunized and uninfected. Immunization with MRLC in TiterMax Gold® adjuvant (group 2) induced a reduction in fluke burdens of 51.0% (p<0.001) when compared with the adjuvant control group, and 61.5% (p<0.001) when compared with the unimmunized infected controls. There was a reduction in fecal egg output in group 2 of 44.8% and 37.3% compared with group 1 and group 3, respectively; although this difference was not statistically significant. Measurement of cytokine levels revealed higher levels of TNF-alpha and IL-2 as well as lower levels of IL-4 in group 2 during the chronic stage of infection (p<0.05), along with higher levels of IFN-gamma during early stages of infection (p<0.05). These results suggest a mixed Th1/Th2 phenotype immune response; however predominance of Th1 cytokines was observed. Levels of anti-MRLC serum IgG in group 2 were significantly higher than controls at the time of euthanasia (p<0.05). This is the first report of immunization with recombinant MRLC in rats, demonstrating that this antigen significantly reduces fluke burdens, increases the Th1 immune response and encourages further studies to improve the vaccine's efficacy.

  1. A unique role of the cholera toxin A1-DD adjuvant for long-term plasma and memory B cell development.

    Science.gov (United States)

    Bemark, Mats; Bergqvist, Peter; Stensson, Anneli; Holmberg, Anna; Mattsson, Johan; Lycke, Nils Y

    2011-02-01

    Adjuvants have traditionally been appreciated for their immunoenhancing effects, whereas their impact on immunological memory has largely been neglected. In this paper, we have compared three mechanistically distinct adjuvants: aluminum salts (Alum), Ribi (monophosphoryl lipid A), and the cholera toxin A1 fusion protein CTA1-DD. Their influence on long-term memory development was dramatically different. Whereas a single immunization i.p. with 4-hydroxy-3-nitrophenyl acetyl (NP)-chicken γ-globulin and adjuvant stimulated serum anti-NP IgG titers that were comparable at 5 wk, CTA1-DD-adjuvanted responses were maintained for >16 mo with a half-life of anti-NP IgG ∼36 wk, but DD dose-dependent increase in germinal center (GC) size and numbers was found, with >60% of splenic B cell follicles hosting GC at an optimal CTA1-DD dose. Roughly 7% of these GC were NP specific. This GC-promoting effect correlated well with the persistence of long-term plasma cells in the bone marrow and memory B cells in the spleen. CTA1-DD also facilitated increased somatic hypermutation and affinity maturation of NP-specific IgG Abs in a dose-dependent fashion, hence arguing that large GC not only promotes higher Ab titers but also high-quality Ab production. Adoptive transfer of splenic CD80(+), but not CD80(-), B cells, at 1 y after immunization demonstrated functional long-term anti-NP IgG and IgM memory cells. To our knowledge, this is the first report to specifically compare and document that adjuvants can differ considerably in their support of long-term immune responses. Differential effects on the GC reaction appear to be the basis for these differences.

  2. Efficacy and Safety Assessment of the Addition of Bevacizumab to Adjuvant Therapy Agents in Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    Directory of Open Access Journals (Sweden)

    Fariba Ahmadizar

    Full Text Available To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients.PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials comparing bevacizumab and adjuvant therapy with adjuvant therapy alone published from January 1966 to 7th of May 2014. Progression free survival, overall survival, overall response rate, safety and quality of life were analyzed using random- or fixed-effects models according to the PRISMA guidelines. We obtained data from 44 randomized controlled trials (30,828 patients. Combining bevacizumab with different adjuvant therapies resulted in significant improvement of progression free survival (log hazard ratio, 0.87; 95% confidence interval (CI, 0.84-0.89, overall survival (log hazard ratio, 0.96; 95% CI, 0.94-0.98 and overall response rate (relative risk, 1.46; 95% CI: 1.33-1.59 compared to adjuvant therapy alone in all studied tumor types. In subgroup analyses, there were no interactions of bevacizumab with baseline characteristics on progression free survival and overall survival, while overall response rate was influenced by tumor type and bevacizumab dose (p-value: 0.02. Although bevacizumab use resulted in additional expected adverse drug reactions except anemia and fatigue, it was not associated with a significant decline in quality of life. There was a trend towards a higher risk of several side effects in patients treated by high-dose bevacizumab compared to the low-dose e.g. all grade proteinuria (9.24; 95% CI: 6.60-12.94 vs. 2.64; 95% CI: 1.29-5.40.Combining bevacizumab with different adjuvant therapies provides a survival benefit across all major subsets of patients, including by tumor type, type of adjuvant therapy, and duration and dose of bevacizumab therapy. Though bevacizumab was associated with increased risks of some adverse drug reactions such as hypertension and bleeding

  3. Stage IB endometrial cancer. Does lymphadenectomy replace adjuvant radiotherapy?

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    Bottke, Dirk; Wiegel, Thomas; Kreienberg, Rolf; Kurzeder, Christian; Sauer, Georg

    2007-11-01

    The role of surgical lymph node dissection and adjuvant radiation therapy (RT) in early stage endometrial cancer is no longer clearly defined. The increased appreciation of lymphadenectomy and the absence of survival advantage from adjuvant RT rise controversies how patients should adequately be treated in stage IB endometrial cancer. The aim of this review is to rule out the validity of either treatment option and determine which preference provides the best therapeutic benefit. Reports of relevant studies obtained from a search of PubMed and studies referenced in those reports were reviewed. Based on the available data in the literature, for stage IB grade 1 or 2, the risk of pelvic relapse is considered too low to justify pelvic RT. However, intravaginal RT (IVRT) should be recommended for those >or= 60 years old or with lymphovascular invasion (LVI). For patients with stage IB grade 3 (and IC all grades), the treatment recommendation is mainly based on whether surgical lymph node staging was performed. These patients have--without surgical lymph node staging--a high risk of pelvic recurrence and should therefore primarily undergo relaparotomy for lymphadenectomy or pelvic RT as second choice. If these patients had a surgical lymph node staging, then IVRT alone is a reasonable alternative to pelvic RT. Overall survival may not be the only ideal endpoint for stage IB endometrial cancer since causes of death are mostly other than endometrial cancer. Conventional pelvic RT may be overtreatment in some patients, in particular in those patients with a large number of negative lymph nodes after lymphadenectomy. However, negative surgical staging should not be understood as adjuvant RT can be omitted in all patients.

  4. Treg inducing adjuvants for therapeutic vaccination against chronic inflammatory diseases

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    Chantal eKeijzer

    2013-08-01

    Full Text Available Many existing therapies in autoimmune diseases are based on systemic suppression of inflammation, the observed side effects illustrate the need for more specific interventions. Regulatory T cells (Treg are pivotal controllers of (autoaggressive immune responses, and decreased Treg numbers and/or functioning have been associated with autoimmune disease. Especially antigen-specific targeting of Treg would enable tailor made interventions, while obviating negative side effects of general immuno-suppression. Self-antigens that participate in inflammation, irrespective of the etiology of the different autoimmune diseases, are held to be candidate antigens for such interventions. Rather than tolerance induction to disease inciting self-antigens, which are frequently unknown, general self-antigens expressed at sites of inflammation would allow targeting of disease independent, but inflammatory-site specific, regulatory mechanisms. Preferably, such self-antigens should be abundantly expressed and up-regulated at the inflammatory site. Heat shock proteins show several of these characteristics.The development of antigen-specific Treg inducing vaccines is a major novel goal in the field of immunotherapy in autoimmune diseases. Progress is hampered by the lack of effective antigens and by the fact that other factors such as dose, route and the presence or absence of an adjuvant, turned out to be critical unknowns, with respect to effective induction of Treg. The use of a Treg inducing adjuvant might be required to achieve effective regulatory responses, in the case of ongoing inflammation. Future goals will be the optimization of natural Treg expansion (or the induction of adaptive Treg without loss of their suppressive function or the concomitant induction of non-regulatory T cells. Here, we discuss the potential use of protein/peptide-based vaccines combined with Treg inducing adjuvants for the development of therapeutic vaccines against chronic

  5. Risk of Marrow Neoplasms After Adjuvant Breast Cancer Therapy: The National Comprehensive Cancer Network Experience

    Science.gov (United States)

    Wolff, Antonio C.; Blackford, Amanda L.; Visvanathan, Kala; Rugo, Hope S.; Moy, Beverly; Goldstein, Lori J.; Stockerl-Goldstein, Keith; Neumayer, Leigh; Langbaum, Terry S.; Theriault, Richard L.; Hughes, Melissa E.; Weeks, Jane C.; Karp, Judith E.

    2015-01-01

    Purpose Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). Patients and Methods We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. Results Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. Conclusion In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy. PMID

  6. The prognosis factor of adjuvant radiation therapy after surgery in uterine sarcomas

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    Hou HL

    2015-08-01

    Full Text Available Hai-Ling Hou, Mao-Bin Meng, Xiu-Li Chen, Lu-Jun Zhao, Li Zhu, Bai-Lin Zhang, Ping Wang Department of Radiation Oncology, CyberKnife Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People’s Republic of China Objective: This retrospective study evaluated the role of adjuvant radiotherapy (AR after surgery in patients with uterine sarcoma and analyzed the prognostic factors of local-regional failure-free survival (LRFFS and overall survival (OS.Patients and methods: A study of a total of 182 patients with uterine sarcoma was conducted between June 1994 and October 2014. Adjuvant radiotherapy was defined as postoperative external beam radiation to the pelvis (30–50 Gray/10–25 fractions at five fractions/week. The primary end point was LRFFS, and the secondary end point was OS. Kaplan–Meier curves were compared using the log-rank test. Cox regression analyses were used to determine prognosticators for LRFFS and OS.Results: The median follow-up time of all patients was 75 months, with a 5-year LRFFS of 62.1%. The 2-year and 5-year LRFFS rates were longer for those who received AR than for those who did not receive AR (83.4% vs 70.3%; 78% vs 55.3%; P=0.013. The 5-year OS of all patients was 56.2%, and no significant differences were observed in the 2-year and 5-year OS rates between these two groups (82.7% vs 71.4%; 64.1% vs 51.7%; P=0.067. Importantly, in patients with leiomyosarcoma, the 2-year and 5-year LRFFS and OS rates were longer for those who received AR than for those who did not receive AR (P=0.04 and P=0.02 for the 2-year and 5-year LRFFS, respectively.Conclusion: Patients with uterine sarcoma who were treated with AR after surgery demonstrated an improved LRFFS compared with those who were treated with surgery alone, especially those patients with leiomyosarcoma. Therefore, the role of personalized adjuvant

  7. Caffeine as an opioid analgesic adjuvant in fibromyalgia

    OpenAIRE

    Scott JR; Hassett AL; Brummett CM; Harris RE; Clauw DJ; Harte SE

    2017-01-01

    J Ryan Scott,1 Afton L Hassett,1 Chad M Brummett,1 Richard E Harris,1,2 Daniel J Clauw,1,2 Steven E Harte1,2 1Chronic Pain and Fatigue Research Center, Department of Anesthesiology, 2Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA Background: Caffeine’s properties as an analgesic adjuvant with nonsteroidal anti-inflammatory drugs/acetaminophen are well documented. However, little clinical research has explored ca­ffeine&a...

  8. Radiation Recall Reaction Induced by Adjuvant Trastuzumab (Herceptin

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    Caroline Chung

    2009-01-01

    trastuzumab (Herceptin administration, there has been no published case of radiation recall reaction associated with trastuzumab. This case describes a clinical presentation consistent with a radiation recall reaction following administration of adjuvant trastuzumab after neoadjuvant FEC-D chemotherapy and locoregional radiotherapy for HER2-positive, locally advanced breast cancer in a premenopausal woman. Although the mechanism and etiology of radiation recall dermatitis remain unclear, this case raises further hypotheses regarding a possible drug dose-dependence and possible predisposing risk factor for the development of radiation recall reactions.

  9. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

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    Ghosn Marwan G

    2010-06-01

    Full Text Available Abstract Background Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. Methods 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. Results This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96% had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy was completed by 22 patients (91.7%. Only 7 patients (36.8% completed the total planned courses of chemotherapy. 2 local relapses (10%, 2 regional relapses (10% and 2 distant relapses (10% were recorded. Time to progression has not been reached. 9 patients (37.5% died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8% with 9 (36% patients suffering grade 3 or 4 toxicity and 5 patients (20% suffering from grade 3 or 4 neutropenia. 4 (17% patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17% and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Conclusions Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the

  10. [Value of adjuvant physiotherapy in postoperative pain management].

    Science.gov (United States)

    Bullmann, V; Weber, T P; Kienle, B; Schulte, T L

    2008-10-01

    In times of limited financial and human resources the application of adjuvant physiotherapy postoperatively in orthopaedic patients requires reevaluation. In the early postoperative course physiotherapy improves the patients' mobility. However, it is not able to reduce the need for pain medication. It is intended to minimize complications and to mobilize and motivate the patients early. In contrast, massages are of minor importance in the immediate postoperative course and are applied only in a few selected cases. Cryotherapy plays a major role especially after shoulder and knee surgery. On the other hand, transcutaneous electrical nerve stimulation (TENS) and acupuncture are applied only in selected patients after orthopaedic surgery, e.g., after limb amputation.

  11. Effect of Feeding Status on Adjuvant Arthritis Severity, Cachexia, and Insulin Sensitivity in Male Lewis Rats

    Directory of Open Access Journals (Sweden)

    Andrea Stofkova

    2010-01-01

    Full Text Available We studied the effect of food restriction, overfeeding, and normofeeding on cachexia, inflammatory and metabolic parameters, and insulin sensitivity in chronic adjuvant arthritis (AA in rats. Food restriction during AA increased circulating ghrelin, corticosterone, decreased leptin, and ameliorated arthrogram score and systemic inflammation compared to normofeeding. Overfeeding worsened arthrogram score and systemic inflammation, and led to lipid accumulation in the liver, but not to alterations of adipokine and ghrelin plasma levels relative to normofeeding. Independently of feeding status, AA induced cachexia, in which modulation of mRNA expressions for appetite-regulating neuropeptides (NPY, AgRP, POMC, CART in the arcuate nucleus (ARC does not play a primary role. The overexpression of IL-1β mRNA in the ARC suggests its role in the mechanisms of impaired energy balance during AA under all feeding conditions. Normal HOMA index in all arthritic groups does not indicate the development of insulin resistance by feeding interventions in these rats.

  12. Our experiment in postoperative adjuvant chemotherapy of endometrial carcinoma. In comparison with radiotherapy on prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Kaichiro; Abe, Kunio; Obata, Koushiro; Inoue, Yoshiki; Hoshiai, Hiroshi [Kinki Univ., Osaka-Sayama (Japan). School of Medicine

    1999-09-01

    To evaluate the usefulness chemotherapy for postoperative adjuvant therapy, authors compared with chemoradiotherapy and the prognosis was analyzed. Patients were 171 cases of endometrial carcinoma which underwent surgery between January 1976 and December 1993. They were accurately determined the surgical stages. In chemoradiotherapy group, patients received irradiation on whole-pelvis or para-aortic lymph nodes after chemotherapy. In the IIIc stage patients, who received combined therapy with chemotherapy (CP or CAP regimen) and radiotherapy, the prognosis was significantly better than those by the chemotherapy alone. The five-year survival rate was 90.9% in chemoradiotherapy group and 50.0% in chemotherapy alone group. The trial on the regimen of chemotherapy and the use of new anti-cancer drugs will be required. (K.H.)

  13. Protective immunization against visceral leishmaniasis using Leishmania sterol 24-c-methyltransferase formulated in adjuvant.

    Science.gov (United States)

    Goto, Yasuyuki; Bogatzki, Lisa Y; Bertholet, Sylvie; Coler, Rhea N; Reed, Steven G

    2007-10-16

    We present here the identification and characterization of Leishmania sterol 24-c-methyltransferase (SMT), as well as data on protection of mice immunized with this Ag formulated in MPL-SE. Serological evaluation revealed that SMT is recognized by VL patients. C57BL/6 mice immunized with this vaccine candidate plus MPL-SE showed Ag-specific Th1 immune responses characterized by robust production of IFN-gamma upon specific Ag re-exposure in vitro. Upon challenge with L. infantum, mice immunized with SMT plus MPL-SE showed significant lower parasite burdens in both spleens and livers compared with non-immunized mice or mice injected with adjuvant alone. The results indicate that SMT/MPL-SE can be an effective vaccine candidate for use against VL.

  14. The potential of 1018 ISS adjuvant in hepatitis B vaccines: HEPLISAV™ review.

    Science.gov (United States)

    Eng, Nelson F; Bhardwaj, Nitin; Mulligan, Rebecca; Diaz-Mitoma, Francisco

    2013-08-01

    Hepatitis B (HBV) virus infects the liver, and upon chronic infection, can cause liver cirrhosis and hepatocellular carcinoma. Despite universal vaccination programs against the virus, HBV still affects over 2 billion people worldwide, with over 240 million developing a chronic infection. While current alum-adjuvanted vaccines have shown efficacy in promoting seroprotection in healthy adults, 5-10% of immune-competent populations fail to achieve long-lasting seroprotection from these formulations. Furthermore, a large proportion of immunocompromised patients fail to achieve seroprotective antibody titers after receiving these vaccines. A novel vaccine candidate, HEPLISAV™, uses immunostimulatory sequences (ISS), in its formulation that helps induce a robust humoral and cell mediated immunity against HBV. In Phase III clinical trials, HEPLISAV™ has been shown to elicit seroprotective antibody titers with fewer immunizations. Similar safety profiles are demonstrated when compared with current HBV vaccines. For these reasons, HEPLISAV™ is an attractive vaccine to combat this global disease.

  15. Effects of simvastatin, ezetimibe, and their combination on histopathologic alterations caused by adjuvant-induced arthritis.

    Science.gov (United States)

    Barbosa, Carmem Patrícia; Ritter, Alessandra Milene; da Silva, Lorena Gimenez; Grespan, Renata; Cuman, Roberto Kenji Nakamura; Hernandes, Luzmarina; Bersani-Amado, Ciomar Aparecida

    2014-08-01

    The objective of the present study was to investigate t