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Sample records for 89b comparing adjuvant

  1. DBCG trial 89B comparing adjuvant CMF and ovarian ablation: similar outcome for eligible but non-enrolled and randomized breast cancer patients

    DEFF Research Database (Denmark)

    Ejlertsen, B.; Jensen, M.B.; Mouridsen, H.T.;

    2008-01-01

    INTRODUCTION: A cohort of premenopausal patients with primary hormone receptor positive breast cancer was prospectively identified to be eligible for the DBCG 89B trial. We perform a long-term follow-up and evaluate the external validity of the trial. MATERIAL AND METHODS: Following registration in...... a population-based registry, patients were invited to be randomized to ovarian ablation (OA) versus nine courses of three-weekly cyclophosphamide, methotrexate and 5-fluorouracil (CMF). The same procedures were used in all patients, including report forms, central review, querying, and analysis of...

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

    Science.gov (United States)

    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.

  3. Preparation and comparative evaluation of different adjuvanted toxoid vaccines against enterotoxaemia

    International Nuclear Information System (INIS)

    The objective of this study was to prepare and evaluate toxoid vaccines against enterotoxaemia in goats. Pure culture of Clostridium perfringens type D was used, already isolated and characterized by Institute of Microbiology, University of Agriculture Faisalabad, Pakistan. Epsilon toxin was extracted; the extracted toxin was subjected to LD/sub 50/ determination and then with the help of formalin inactivation was done. The resulting toxoids were adjuvanted with two adjuvants including Montanide ISA 206 and Aluminium hydroxide gel (Alum). The pathogenicity and immunogenicity of prepared toxoid vaccines and commercial vaccine procured from VRI, Lahore, Pakistan were studied and compared initially in an experimental trial on rabbits and then in field trials on goat. Field trial was conducted on 72 goats divided into four equal groups (n=18). The Indirect Haemagglutination Test (IHA) was used to evaluate the antibody titer and challenge protection test was performed in rabbits. The results showed that antibody titers were significantly higher (P< 0.05) for in group vaccinated with Montanide ISA -206 adjuvanted toxoid vaccine. The geometric mean titer of Montanide group was 203.19, 456 and 670 at 14, 21 and 28 days post vaccination as compared to 181.02, 298.63 and 456.14 of Alum group on same days. Montanide vaccinated group also exhibited highest protection percentage (100%) post challenge as compared to 85.71%, 71.42% and 14.29% of group B, C and D, respectively. (author)

  4. Increased immunogenicity of the MF59-adjuvanted influenza vaccine compared to a conventional subunit vaccine in elderly subjects

    International Nuclear Information System (INIS)

    Three-hundred and eight outpatient elderly subjects (≥ 65 years) were randomly assigned to receive the MF59-adjuvanted influenza vaccine (FLUAD; n = 204) or a conventional subunit influenza vaccine (AGRIPPAL S1; n = 104) in order to compare the safety and immunogenicity of the two vaccines. Although mild pain at the injection site was reported more frequently by subjects immunised with the adjuvanted vaccine, both vaccines were shown to be safe and well tolerated. The adjuvanted vaccine was more immunogenic as indicated by higher post-immunisation geometric mean titres (GMTs) and by higher proportions of subjects with post-immunisation ≥ four fold increases of antibody titres or subjects with ≥ 1/160 post-immunisation HI titres. These differences, statistically significant for all three strains after immunisation, indicated that, by addition of the MF59 adjuvant emulsion, conventional subunit influenza antigens acquire an enhanced immunogenicity without any clinically significant increase of their reactogenicity

  5. 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

  6. 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

  7. 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.

  8. 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

    2014-01-01

    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

  9. 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

  10. 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.

  11. 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.

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

    CERN Document Server

    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.

  13. Adjuvant chemotherapy in early breast cancer.

    Science.gov (United States)

    Ejlertsen, Bent

    2016-05-01

    these CMF regimens has not been compared within the context of a randomised trial. Shifting from the 77B's classic CMF regimen to the 82B four-weekly IV regimen or the 89B three-weekly IV regimen was associated with a 30% increased risk of a DFS event in a multivariate analysis of a population-based cohort study. Furthermore, the four-weekly regimen used in 82B was associated with a 40% increase in mortality. The strengths of the design include identical selection criteria, uniform and prospective registration of treatment, tumour and patient characteristics. Caution is still required due to the non-experimental design of the comparison. Another finding was a substantial difference in the risk of amenorrhoea; and while 15% 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 cancer patients with ER-positive tumours. No significant differences were found in DFS or OS in the preplanned analysis, suggesting that the benefits of CMF may, at least in part, be explained by ovarian suppression in premenopausal patients with ER-positive tumours. However, these results 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 and the EBCTCG meta-analyses. The benefits obtained with any individual anticancer drug are largely determined by the cancer (somatic) genome; and by being a molecular target of anthracyclines, TOP2A aberrations could obviously be associated with cancer drug benefits. In the DBCG 89D, a significant heterogeneity was observed between a beneficial effect on DFS and OS

  14. 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

  15. Quality of life of advanced ovarian cancer patients in the randomized phase III study comparing primary debulking surgery versus neo-adjuvant chemotherapy

    NARCIS (Netherlands)

    Greimel, E.; Kristensen, G.B.; Burg, M.E.L. van der; Coronado, P.; Rustin, G.; Rio, A.S. del; Reed, N.S.; Nordal, R.R.; Coens, C.; Vergote, I.; Massuger, L.F.A.G.; Ottevanger, P.B.

    2013-01-01

    OBJECTIVE: The EORTC 55971 trial compared primary debulking surgery (PDS) versus neo-adjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). The impact of both treatment arms on quality of life (QOL) is reported. METHODS: Patients with stages IIIc or IV ovarian cancer completed th

  16. Comparative study on the efficacy of tamoxifen and letrozole in the adjuvant hormonal therapy of postmenopausal breast cancer

    Institute of Scientific and Technical Information of China (English)

    Mei Yang

    2016-01-01

    Objective:To explore the efficacy of tamoxifen and letrozole in the adjuvant hormonal therapy of postmenopausal breast cancer.Methods:A total of 60 patients with postmenopausal breast cancer who were admitted in our hospital from May, 2012 to May, 2015 were included in the study and randomized into the observation group and the control group. The patients in the observation group were given letrozole, while the patients in the control group were given tamoxifen. The change of serum VEGF level before and after treatment, the mass shrinking degree after treatment, and the change of tumor grading in the two groups were observed. The clinical efficacy and adverse reactions were compared.Results:After treatment, the serum VEGF level in the observation group [(145.79±41.28) pg/mL] was significantly lower than that in the control group [(214.62±53.51) pg/mL]. The mass shrinking degree in the observation group (56.89±15.43) was significantly greater than that in the control group (45.17±11.16). In the tumor grading, 46.67% (14/30) at stage I in the observation group was significantly greater than that in the control group [13.33% (4/30)], 13.33% (4/30) at stage III significantly less than that in the control group [36.67% (11/30)] . The total response rate in the observation group [90.00% (27/30)] was significantly higher than that in the control group [66.66% (20/30)]. Conclusions:In the neoadjuvant endocrine therapy of postmenopausal breast cancer, letrozole has a better effect than tamoxifen, and can significantly reduce the tumor grading; therefore, it deserves to be widely recommended in the clinic.

  17. Comparative evaluation of low-level laser and systemic steroid therapy in adjuvant-enhanced arthritis of rat temporomandibular joint: A histological study

    OpenAIRE

    Khozeimeh, Faezeh; Moghareabed, Ahmad; Allameh, Maryam; Baradaran, Shahrzad

    2015-01-01

    Background: Low-level laser therapy (LLLT) has shown a promising effect in ameliorating symptoms of rheumatoid arthritis (RA). The aim of this investigation was to compare the early and late anti-inflammatory effects of LLLT and betamethasone in RA. Materials and Methods: In this animal experimental study, after inducing a model of RA in temporomandibular joint (TMJ) of 37 Wistar rats using adjuvant injection, they were randomly distributed into three experimental groups of 12 animals each: (...

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

    DEFF Research Database (Denmark)

    Billeskov, Rolf; Christensen, Jan Pravsgaard; Aagaard, Claus;

    2013-01-01

    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...

  19. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective

    OpenAIRE

    Barlesi, Fabrice; Chouaid, Christos; Crequit, Jacky; Le Caer, Hervé; Pujol, Jean Louis; Legodec, Julien; Vergnenegre, Alain; Le Treut, Jacques; Fabre-Guillevin, Elizabeth; Loundou, Anderson; Auquier, Pascal; Simeoni, Marie-Claude; Thomas, Pascal A

    2015-01-01

    International audience OBJECTIVES: Adjuvant chemotherapy with vinorelbine plus cisplatin (VC) improves survival in resected non-small-cell lung cancer (NSCLC), but has negative impact on quality of life (QoL). In advanced NSCLC, gemcitabine plus cisplatin (GC) and docetaxel plus cisplatin (DC) exhibit comparable efficacy, with possibly superior QoL compared to VC. This trial investigated these regimens in the adjuvant setting. METHODS: Patients with Stage IB to III NSCLC were eligible foll...

  20. 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.

  1. Randomized controlled trial to evaluate the effects of progressive resistance training compared to progressive muscle relaxation in breast cancer patients undergoing adjuvant radiotherapy: the BEST study

    International Nuclear Information System (INIS)

    Cancer-related fatigue (CRF) is one of the most common and distressing side effects of cancer and its treatment. During and after radiotherapy breast cancer patients often suffer from CRF which frequently impairs quality of life (QoL). Despite the high prevalence of CRF in breast cancer patients and the severe impact on the physical and emotional well-being, effective treatment methods are scarce. Physical activity for breast cancer patients has been reported to decrease fatigue, to improve emotional well-being and to increase physical strength. The pathophysiological and molecular mechanisms of CRF and the molecular-biologic changes induced by exercise, however, are poorly understood. In the BEST trial we aim to assess the effects of resistance training on fatigue, QoL and physical fitness as well as on molecular, immunological and inflammatory changes in breast cancer patients during adjuvant radiotherapy. The BEST study is a prospective randomized, controlled intervention trial investigating the effects of a 12-week supervised progressive resistance training compared to a 12-week supervised muscle relaxation training in 160 patients with breast cancer undergoing adjuvant radiotherapy. To determine the effect of exercise itself beyond potential psychosocial group effects, patients in the control group perform a group-based progressive muscle relaxation training. Main inclusion criterion is histologically confirmed breast cancer stage I-III after lumpectomy or mastectomy with indication for adjuvant radiotherapy. Main exclusion criteria are acute infectious diseases, severe neurological, musculosceletal or cardiorespiratory disorders. The primary endpoint is cancer-related fatigue; secondary endpoints include immunological and inflammatory parameters analyzed in peripheral blood, saliva and urine. In addition, QoL, depression, physical performance and cognitive capacity will be assessed. The BEST study is the first randomized controlled trial comparing progressive

  2. 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.

  3. Toxicity of an herbicide and adjuvant to saltmarsh invertebrates in the management of invasive grass; Comparative laboratory and field tests.

    Science.gov (United States)

    Kleinhenz, Linda S; Nugegoda, Dayanthi; Verspaandonk, Emily R; Coombes, Darcy C; Howe, Steffan; Shimeta, Jeff

    2016-08-15

    Coastal weeds are often treated with herbicides without knowledge of non-target impacts, and toxicity data from standardized test species can have limited applicability. We evaluated toxicity to invertebrates from Fusilade Forte® and the adjuvant Hasten® in the control of invasive salt marsh grass, Spartina anglica. For 3 of 4 local invertebrates, Fusilade Forte® was moderately toxic (96h LC50 5.4-144mgL(-1)), whereas Hasten® was less toxic (14.2-450mgL(-1)). For most species, the mixture was more toxic than the herbicide alone, with 96h LC50 reduced 23-45%. However, a field experiment applying typical concentrations (1000×the lowest 96h LC50) showed low concentrations of herbicide residues and no detrimental impacts on invertebrates over 6months. The results reveal the importance of testing locally relevant species for potential toxicity, and of comparison tests with field exposures to determine the realised toxicity in nature. PMID:27262496

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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....

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Pay more attention to the immunologically comparative evaluation of HIV-1 DNA vaccine in combination with adjuvant cytokines: a long way to go

    Institute of Scientific and Technical Information of China (English)

    REN Xiao-feng

    2006-01-01

    @@ To the Editor: A recent article entitled "HIV-1 DNA vaccine with adjuvant cytokines induces specific immune responses against HIV-1 infection in mice"was published in the Chinese Medical Journal.1 The authors descriptively analyzed the adjuvant potential of an interleukin-12 (IL-12), interleukin-18 (IL-18),regulated on activation of normal T-cell expressed and secreted factor (RANTES), macrophage inflammatory protein 1 alpha (MIP-1α) or stromal cell derived factor 1 (SDF-1) plasmid when coimmunized with an HIV Gag gene-based DNA vaccine. Consequently the authors believed that IL-12, IL-18, or SDF-1 plasmid DNA potentially serves as immune adjuvants in combination with therapeutic HIV-1 DNA vaccine. The RANTES,MIP-1α plasmid DNA potentially serves as immune adjuvants in combination with HIV-1 prophylactic vaccine. Although the experiment allows us to consider such a coinoculation strategy as one of the means against HIV-1 infection, some special attentions should be highlighted.

  9. Adjuvant therapy of melanoma.

    Science.gov (United States)

    Agarwala, S S; Kirkwood, J M

    1998-06-01

    Patients with AJCC Stage IIB and III melanoma have a poor 5-year survival rate which has been the driving force behind attempts to find an effective adjuvant therapy for this stage of disease that would effectively reduce relapse and improve survival. Immunotherapy with bacillus Calmette-Guerin (BCG), Corynebacterium parvum, and levamisole have not been successful in achieving this goal, nor have trials with chemotherapy in the adjuvant setting, including high-dose chemotherapy with autologous bone marrow transplantation. The recent Eastern Cooperative Oncology Group (ECOG) 1684 study showed significant improvement in relapse-free and overall survival with high doses of alpha interferon (IFNalpha) given for 1 year. Lower dosages of IFNalpha have to date been unsuccessful in impacting upon long-term survival. Recent data with vaccines have been encouraging, and the GM2-KLH vaccine is the focus of ongoing intergroup study comparing this treatment with IFNalpha in resected Stage IIB and III melanoma. The various regimens are reviewed in this article. PMID:9588723

  10. 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.

  11. Comparative efficacy of virus like particle (VLP) vaccine of foot-and-mouth-disease virus (FMDV) type O adjuvanted with poly I:C or CpG in guinea pigs.

    Science.gov (United States)

    Terhuja, Megolhubino; Saravanan, Paramasivam; Tamilselvan, Ramasamy Periyasamy

    2015-11-01

    Foot-and-mouth disease (FMD) is one of the most contagious and economically important diseases of cloven-hoofed livestock. Currently used inactivated FMD vaccines have short lived immunity besides risk of handling live virus. We studied recombinant FMD virus like particles (VLPs) encoded by FMDV type O/IND/R2/75 polyprotein genes expressed in Sf9 cells and adjuvanted with CpG or Poly I:C in inducing protective immune response in guinea pigs. Guinea pigs immunized with VLP + CpG vaccine had shown markedly higher cell mediated immunity (CMI) in comparison to the conventional vaccine group as evident from higher levels of IgG2 than IgG1. Although the humoral response was less in VLP + CpG compared to conventional vaccine, the lymphocyte stimulation index was more in VLP + CpG compared to conventional and VLP + Poly I:C vaccine groups. Finally the challenge experiments on 28 and 56 dpv had shown 75% protection in VLP + CpG immunized guinea pigs primary and boosted animals, while 50% and 62% protection in VLP + Poly I:C in primary and boosted animals, respectively. In conclusion, CpG adjuvant was found to be superior followed by ISA206 and Poly I:C in eliciting protection in VLP based FMD vaccines in guinea pigs. PMID:26493006

  12. Comparative efficacy of ropivacaine and levobupivacaine in combined femoral and lateral femoral cutaneous nerve block with adjuvant magnesium for post-operative analgesia

    Directory of Open Access Journals (Sweden)

    Prakash Khairnar

    2016-01-01

    Full Text Available Background and Aims: Patients with burns may require multiple surgeries, but poor general condition and underlying protein energy malnutrition make them unsuitable candidates for general or spinal anaesthesia. This study evaluated the role of magnesium sulphate as an adjuvant with levobupivacaine and ropivacaine used in combined femoral and lateral femoral cutaneous nerve (LFCN blocks in burn patients with relative sparing of thigh portion. Methods: This prospective, randomised, double-blind study included 54 adult patients of 18-65 years age, undergoing split-thickness skin graft harvest from the thigh, allotted to three equal groups of 18 each. Group L patients received femoral nerve (FN block with 15 mL of 0.5% levobupivacaine and 8 mL for LFCN block; Group LM patients received 14 mL of 0.5% levobupivacaine along with 1.0 mL of 15% magnesium sulphate for FN block, 7.5 mL of 0.5% levobupivacaine with 0.5 mL of 15% of magnesium sulphate to LFCN block and Group R patients received 15 mL of 0.5% ropivacaine for FN block and 8 mL of 0.5% ropivacaine for LFCN block. Time to block onset and complete surgical block, duration of analgesia, total analgesic dose and the overall analgesia satisfaction score were measured in the first 24 h post-operatively. Quantitative data were analysed with ANOVA and qualitative data subjected to Chi-square tests. Intergroup comparison was performed with independent t-test. Results: The duration of post-operative analgesia did not differ with the addition of magnesium (P = 0.610. Time to onset of the block was significantly decreased with the addition of magnesium (P = 0.0341, but time to complete surgical block onset was similar across the groups. Conclusion: Both ropivacaine and levobupivacaine have good perioperative analgesic efficacy. Magnesium as an analgesia adjuvant with levobupivacaine does not prolong the duration of post-operative analgesia.

  13. 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 .

  14. 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.

  15. 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.

  16. An Update of the Phase III Trial Comparing Whole Pelvic to Prostate Only Radiotherapy and Neoadjuvant to Adjuvant Total Androgen Suppression: Updated Analysis of RTOG 94-13, With Emphasis on Unexpected Hormone/Radiation Interactions

    International Nuclear Information System (INIS)

    Purpose: This trial was designed to test the hypothesis that total androgen suppression and whole pelvic radiotherapy (WPRT) followed by a prostate boost improves progression-free survival (PFS) by ≥10% compared with total androgen suppression and prostate only RT (PORT). This trial was also designed to test the hypothesis that neoadjuvant hormonal therapy (NHT) followed by concurrent total androgen suppression and RT improves PFS compared with RT followed by adjuvant hormonal therapy (AHT) by ≥10%. Methods and Materials: Patients eligible for the study included those with clinically localized adenocarcinoma of the prostate and an elevated prostate-specific antigen level of 15%. Results: The difference in overall survival for the four arms was statistically significant (p = 0.027). However, no statistically significant differences were found in PFS or overall survival between NHT vs. AHT and WPRT compared with PORT. A trend towards a difference was found in PFS (p = 0.065) in favor of the WPRT + NHT arm compared with the PORT + NHT and WPRT + AHT arms. Conclusions: Unexpected interactions appear to exist between the timing of hormonal therapy and radiation field size for this patient population. Four Phase III trials have demonstrated better outcomes when NHT was combined with RT compared with RT alone. The Radiation Therapy Oncology Group 9413 trial results have demonstrated that when NHT is used in conjunction with RT, WPRT yields a better PFS than does PORT. It also showed that when NHT + WPRT results in better overall survival than does WPRT + short-term AHT. Additional studies are warranted to determine whether the failure to demonstrate an advantage for NHT + WPRT compared with PORT + AHT is chance or, more likely, reflects a previously unrecognized biologic phenomenon

  17. 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...

  18. Adjuvant Therapy Trials.

    Science.gov (United States)

    Ursem, Carling; Van Loon, Katherine; Venook, Alan

    2016-01-01

    In 2015, ramucirumab and TAS-102 became the 10th and 11th drugs approved by the Food and Drug administration for the treatment of patients with colorectal cancer, not counting leucovorin, and yet only 3 agents, 5-fluorouracil, capecitabine, and oxaliplatin, have proven benefit in adjuvant treatment. In fact, there have been no additions (and 1 subtraction levamisole) to our arsenal of therapies for patients with stages II and III colon cancer for more than a decade. How did we get here? Are we stuck? And how do we move forward? PMID:27341598

  19. 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

  20. Iyengar-Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Therapy in Women with Stage I–III Breast Cancer: Health-Related Quality of Life, Mindfulness, Spirituality, Life Satisfaction, and Cancer-Related Fatigue

    Science.gov (United States)

    Lötzke, Désirée; Wiedemann, Florian; Rodrigues Recchia, Daniela; Ostermann, Thomas; Sattler, Daniel; Ettl, Johannes; Kiechle, Marion; Büssing, Arndt

    2016-01-01

    This study aims to test the effects of yoga on health-related quality of life, life satisfaction, cancer-related fatigue, mindfulness, and spirituality compared to conventional therapeutic exercises during (neo)adjuvant cytotoxic and endocrine therapy in women with breast cancer. In a randomized controlled trial 92 women with breast cancer undergoing oncological treatment were randomly enrolled for a yoga intervention (YI) (n = 45) or for a physical exercise intervention (PEI) (n = 47). Measurements were obtained before (t0) and after the intervention (t1) as well as 3 months after finishing intervention (t2) using standardized questionnaires. Life satisfaction and fatigue improved under PEI (p < 0.05) but not under YI (t0 to t2). Regarding quality of life (EORTC QLQ-C30) a direct effect (t0 to t1; p < 0.001) of YI was found on role and emotional functioning, while under PEI only emotional functioning improved. Significant improvements (p < 0.001) were observed at both t1 and t2 also for symptom scales in both groups: dyspnea, appetite loss, constipation, and diarrhea. There was no significant difference between therapies for none of the analyzed variables neither for t1 nor for t2. During chemotherapy, yoga was not seen as more helpful than conventional therapeutic exercises. This does not argue against its use in the recovery phase. PMID:27019663

  1. Role of mammography in evaluating residual cancer of locally advanced breast carcinoma after neo-adjuvant chemotherapy : compared with clinical examination

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Byoung Wook; Kim, Eun Kyung; Oh, Ki Keun; Cho, Jae Min; Chung, Hyun Cheol; Lee, Byung Chan; Lee, Kyong Sik; Lee, Yong Hee [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-06-01

    To compare the usefulness of mammography and clinical examination in the evaluation of residual cancer of locally-advanced breast carcinoma treated with neoadjuvant chemotherapy. Among 67 patients with locally advanced breast carcinoma who were treated with neoadjuvant chemotherapy, 18, aged 35-67 (mean, 48) years, underwent mammography before and after this therapy. The 18 sets of mammographs were analyzed retrospectively and compared with the results of clinical examination based on histologic diagnosis. On histologic examinations, 16 of 18 patients (89%) were found to have residual cancer, but in one of these 16, mammography did not show this same result. On mammography, residual cancer was found in 16 patients, but in one of this group, histologic examination did not reveal the same finding. Clinically, a complete response was shown by four patients, and a partial response by 11 ; three showed no response. On histolgogic examination, three of the four patients with complete clinical response were found to have residual cancer. Post-treatment mammographic findings showed that 11 patients had measurable mass ; all of these had residual cancer (positive predictive value : 100%). However, five of seven patients in whom no measurable mass was evident also had residual cancer. Seven of 8 patients in whom microcalcifications were seen on mammography were found to have residual cancer (positive predictive value : 88%). The sensitivity of mammography in predicting residual cancer was greater than that of clinical examination (94% vs 81%), even when microscopic residual cancer was considered as a complete response (92% vs 77%). The specificity of mammography was the same as that of clinical examination(50% vs 50%, 20% vs 20%). In evaluating residual cancer of locally-advanced breast carcinoma after neoadjuvant chemotheragy, mammography is more accurate and informative than clincal examination. In predicting residual cancer, however, it is not accurate enough to replace

  2. 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.

  3. QUALITY OF LIFE OF WOMEN RECIEVING ADJUVANT HORMONAL TREATMENT FOR BREAST CANCER – A RANDOMIZED TRIAL COMPARING TAMOXIFEN WITH AROMATASE INHIBITORS

    Directory of Open Access Journals (Sweden)

    C. Volovat

    2011-05-01

    Full Text Available Purpose: The assessment and comparison of the quality of life in women with early stages breast cancer receiving Tamoxifen versus aromatase inhibitors (AINs. Methods: There were selected 223 patients treated at Center of Medical Oncology Iasi, with early stages breast cancer. The patients were divided in two groups: 115 patients receiving Tamoxifen and 107 patients receiving aromatase inhibitors. From the patients receiving AINs, 33 of patients have received Exemestane, 60 patients Letrozole and 14 patients Anastrazole. The patients have completed an EORTC C30 and EORTC BR23 questionnaire at the beginning of the treatment (after one month and after 2 years of treatment. There was calculated the difference related with global status, functional scales, emotional scales, cognitive scales and symptom scales. Results: Statistic results show a better quality of life for Anastrazole vs. Letrozole and for AINs vs. Tamoxifen group, mainly on physical scales both after 2 months and after 2 years of treatment. In the same time, the physical scales were with better results after 1 month of treatment vs. 2 years of treatment. Conclusions: Following the hormonal treatment period, there is a mild worsening of quality of life for Tamoxifen and AINs too. In the same time, the quality of life is better in the group with AINs treatment comparative with the Tamoxifen treatment.

  4. 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.

  5. 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.

  6. Cognitive function after adjuvant treatment for early breast cancer

    DEFF Research Database (Denmark)

    Debess, Jeanne; Riis, Jens Østergaard; Engebjerg, Malene Cramer;

    2010-01-01

    start of adjuvant treatment and after 6 months by neuropsychological tests and questionnaires to evaluate cognitive function, quality of life and psychological distress. Neuropsychological tests did not reveal any differences in cognitive function between breast cancer patients after chemotherapy and......The purpose of this study was to examine cognitive function in patients with early breast cancer before and after adjuvant chemotherapy or 6 months of tamoxifen. We performed a population-based study in the county of North Jutland, Denmark, including 120 women aged <60 years who received adjuvant...... chemotherapy with seven cycles of cyclophosphamide, epirubicin and fluoruracil or adjuvant tamoxifen for 6 months for early breast cancer from 2004 to 2006. They were compared with an aged-matched group of 208 women without previous cancer selected randomly from the same population. Data were collected before...

  7. Liposome-Based Adjuvants for Subunit Vaccines

    DEFF Research Database (Denmark)

    Tandrup Schmidt, Signe; Foged, Camilla; Rades, Thomas

    2016-01-01

    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...... 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...

  8. 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...

  9. Innate immunity and adjuvants.

    Science.gov (United States)

    Akira, Shizuo

    2011-10-12

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  10. Adjuvant Therapy of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Chakra P Chaulagain

    2011-07-01

    Full Text Available There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This year at the American Society of Clinical Oncology (ASCO Gastrointestinal Cancer Symposium, the randomized phase III study presented by Uesaka et al. from Japan (Abstract #145 represents a newer paradigm of oral adjuvant S-1 chemotherapy in place of the traditional standard of care intravenous gemcitabine in terms of prolonging patients’ survival. Another study by Fan et al. (Abstract #269 examined the value of targeted therapy using erlotinib with adjuvant chemoradiation and chemotherapy. We present the summary of these two studies and discuss the potential impact on our clinical practice on this highly lethal cancer.

  11. 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.

  12. 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.

  13. Adjuvant therapy of malignant melanoma.

    Science.gov (United States)

    Molife, R; Hancock, B W

    2002-10-01

    High risk surgically resected melanoma is associated with a less than 50% 5-year survival. Adjuvant therapy is an appropriate treatment modality in this setting, and is more likely to be effective as the tumour burden here is small. Clinical observations of spontaneous tumour regressions and a highly variable rate of disease progression suggest a role of the immune system in the natural history of melanoma. Biological agents have therefore been the subjects of numerous adjuvant studies. Early, randomised controlled trials (RCTs) of Bacillus Calmette-Guerin (BCG), levamisole, Corynebacterium parvum, chemotherapy, isolated limb perfusion (ILP), radiotherapy, transfer factor (TF), megestrol acetate and vitamin A yielded largely negative results. Current trials focus on vaccines and the interferons. To date the latter is the only therapy to have shown a significant benefit in the prospective randomised controlled phase III setting. This report represents a systematic review of studies in adjuvant therapy in melanoma. Data from ongoing studies is awaited before a role for adjuvant agents in high risk melanoma is confirmed. PMID:12399001

  14. Improving vaccine delivery using novel adjuvant systems.

    Science.gov (United States)

    Pichichero, Michael E

    2008-01-01

    Adjuvants have been common additions to vaccines to help facilitate vaccine delivery. With advancements in vaccine technology, several adjuvants which activate immune specific responses have emerged. Available data show these adjuvants elicit important immune responses in both healthy and immunocompromised populations, as well as the elderly. Guidelines for the use and licensure of vaccine adjuvants remain under discussion. However, there is a greater understanding of the innate and adaptive immune response, and the realization of the need for immune specific adjuvants appears to be growing. This is a focused review of four adjuvants currently in clinical trial development: ASO4, ASO2A, CPG 7907, and GM-CSF. The vaccines including these adjuvants are highly relevant today, and are expected to reduce the disease burden of cervical cancer, hepatitis B and malaria. PMID:18398303

  15. Does Adjuvant Radiotherapy Suppress Liver Regeneration After Partial Hepatectomy?

    International Nuclear Information System (INIS)

    Purpose: To analyze the influence of the adjuvant radiotherapy (RT) on the liver regeneration and liver function after partial hepatectomy (PH). Methods and Materials: Thirty-four patients who underwent PH for biliary tract cancer between October 2003 and July 2005 were reviewed. Hemihepatectomy was performed in 14 patients and less extensive surgery in 20. Of the patients, 19 patients had no adjuvant therapy (non-RT group) and 15 underwent adjuvant RT by a three-dimensional conformal technique (RT group). Radiation dose range was 40 to 50 Gy (median, 40 Gy). Liver volume on computed tomography and the results of liver function tests at 1, 4, 12, 24, and 52 weeks after PH were compared between the RT and non-RT groups. Results: The preoperative characteristics were identical for both groups. During the interval between Weeks 4 and 12 when adjuvant RT was delivered in the RT group, the increase in liver volume was significantly smaller in the RT group than non-RT group (22.9 ± 38.3cm3 and 81.5 ± 75.6cm3, respectively, p = 0.007). However, the final liver volume measured at 1 year after PH did not differ between the two groups (p = 0.878). Liver function tests were comparable for both groups. The resection extent and original liver volume was independent factors for final liver volume measured at 1 year after PH. Conclusions: In this study, adjuvant RT delayed the liver regeneration process after PH, but the volume difference between the two study groups became nonsignificant after 1 year. Adjuvant RT had no additional adverse effect on liver function after PH.

  16. Adjuvant Therapy of Pancreatic Cancer

    OpenAIRE

    Chakra P Chaulagain; Muhammad Wasif Saif; Goodman, Martin D.; John Ng

    2011-01-01

    There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This year at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposiu...

  17. Effect of particulate adjuvant on the anthrax protective antigen dose required for effective nasal vaccination.

    Science.gov (United States)

    Bento, Dulce; Staats, Herman F; Borges, Olga

    2015-07-17

    Successful vaccine development is dependent on the development of effective adjuvants since the poor immunogenicity of modern subunit vaccines typically requires the use of potent adjuvants and high antigen doses. In recent years, adjuvant formulations combining both immunopotentiators and delivery systems have emerged as a promising strategy to develop effective and improved vaccines. In this study we investigate if the association of the mast cell activating adjuvant compound 48/80 (C48/80) with chitosan nanoparticles would promote an antigen dose sparing effect when administered intranasally. Even though the induction of strong mucosal immunity required higher antigen doses, incorporation of C48/80 into nanoparticles provided significant dose sparing when compared to antigen and C48/80 in solution with no significant effect on serum neutralizing antibodies titers. These results suggest the potential of this novel adjuvant combination to improve the immunogenicity of a vaccine and decrease the antigen dose required for vaccination. PMID:26087299

  18. 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....... Data on patients with stage III colonic cancer operated between January 1, 2005 and August 31, 2012 were retrieved. Perioperative variables, surgical modality, and time to adjuvant therapy (8 weeks) were evaluated and Cox regression was performed to identify factors influencing survival....... 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...

  19. Silica Nanoparticles as the Adjuvant for the Immunisation of Mice Using Hepatitis B Core Virus-Like Particles

    OpenAIRE

    Dace Skrastina; Ivars Petrovskis; Ilva Lieknina; Janis Bogans; Regina Renhofa; Velta Ose; Andris Dishlers; Yuri Dekhtyar; Paul Pumpens

    2014-01-01

    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 immunisatio...

  20. 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

  1. 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...... 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...

  2. Systemic adjuvant therapies in renal cell carcinoma

    OpenAIRE

    Sebastiano Buti; Melissa Bersanelli; Maddalena Donini; Andrea Ardizzoni

    2012-01-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to d...

  3. Adjuvant auricular electroacupuncture and autogenic training in rheumatoid arthritis: a randomized controlled trial

    DEFF Research Database (Denmark)

    Bernateck, M.; Becker, M.; Schwacke, C.;

    2008-01-01

    BACKGROUND: In contrast to psychological interventions the usefulness of acupuncture as an adjuvant therapy in rheumatoid arthritis (RA) has not yet been demonstrated. OBJECTIVE: The efficacy of auricular electroacupuncture (EA) was directly compared with autogenic training (AT). METHODS: Patients...

  4. 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.

  5. 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

  6. 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

  7. 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....

  8. Chitosan and Sodium Alginate Combinations Are Alternative, Efficient, and Safe Natural Adjuvant Systems for Hepatitis B Vaccine in Mouse Model

    Science.gov (United States)

    AbdelAllah, Nourhan H.; Boseila, Abeer A.; Amin, Magdy A.

    2016-01-01

    Hepatitis B viral (HBV) infections represent major public health problem and are an occupational hazard for healthcare workers. Current alum-adjuvanted HBV vaccine is the most effective measure to prevent HBV infection. However, the vaccine has some limitations including poor response in some vaccinee and being a frost-sensitive suspension. The goal of our study was to use an alternative natural adjuvant system strongly immunogenic allowing for a reduction in dose and cost. We tested HBV surface antigen (HBsAg) adjuvanted with chitosan (Ch) and sodium alginate (S), both natural adjuvants, either alone or combined with alum in mouse model. Mice groups were immunized subcutaneously with HBsAg adjuvanted with Ch or S, or triple adjuvant formula with alum (Al), Ch, and S, or double formulations with AlCh or AlS. These were compared to control groups immunized with current vaccine formula or unadjuvanted HBsAg. We evaluated the rate of seroconversion, serum HBsAg antibody, IL-4, and IFN-γ levels. The results showed that the solution formula with Ch or S exhibited comparable immunogenic responses to Al-adjuvanted suspension. The AlChS gave significantly higher immunogenic response compared to controls. Collectively, our results indicated that Ch and S are effective HBV adjuvants offering natural alternatives, potentially reducing dose. PMID:27493674

  9. In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant.

    Science.gov (United States)

    van Haren, Simon D; Ganapathi, Lakshmi; Bergelson, Ilana; Dowling, David J; Banks, Michaela; Samuels, Ronald C; Reed, Steven G; Marshall, Jason D; Levy, Ofer

    2016-07-01

    Most infections occur in early life, prompting development of novel adjuvanted vaccines to protect newborns and infants. Several Toll-like receptor (TLR) agonists (TLRAs) are components of licensed vaccine formulations or are in development as candidate adjuvants. However, the type and magnitude of immune responses to TLRAs may vary with the TLR activated as well as age and geographic location. Most notably, in newborns, as compared to adults, the immune response to TLRAs is polarized with lower Th1 cytokine production and robust Th2 and anti-inflammatory cytokine production. The ontogeny of TLR-mediated cytokine responses in international cohorts has been reported, but no study has compared cytokine responses to TLRAs between U.S. neonates and infants at the age of 6months. Both are critical age groups for the currently pediatric vaccine schedule. In this study, we report quantitative differences in the production of a panel of 14 cytokines and chemokines after in vitro stimulation of newborn cord blood and infant and adult peripheral blood with agonists of TLR4, including monophosphoryl lipid A (MPLA) and glucopyranosyl lipid Adjuvant aqueous formulation (GLA-AF), as well as agonists of TLR7/8 (R848) and TLR9 (CpG). Both TLR4 agonists, MPLA and GLA-AF, induced greater concentrations of Th1 cytokines CXCL10, TNF and Interleukin (IL)-12p70 in infant and adult blood compared to newborn blood. All the tested TLRAs induced greater infant IFN-α2 production compared to newborn and adult blood. In contrast, CpG induced greater IFN-γ, IL-1β, IL-4, IL-12p40, IL-10 and CXCL8 in newborn than in infant and adult blood. Overall, to the extent that these in vitro studies mirror responses in vivo, our study demonstrates distinct age-specific effects of TLRAs that may inform their development as candidate adjuvants for early life vaccines. PMID:27081760

  10. 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.

  11. 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.

  12. 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.

  13. Potent response of QS-21 as a vaccine adjuvant in the skin when delivered with the Nanopatch, resulted in adjuvant dose sparing.

    Science.gov (United States)

    Ng, Hwee-Ing; Fernando, Germain J P; Depelsenaire, Alexandra C I; Kendall, Mark A F

    2016-01-01

    Adjuvants play a key role in boosting immunogenicity of vaccines, particularly for subunit protein vaccines. In this study we investigated the induction of antibody response against trivalent influenza subunit protein antigen and a saponin adjuvant, QS-21. Clinical trials of QS-21 have demonstrated the safety but, also a need of high dose for optimal immunity, which could possibly reduce patient acceptability. Here, we proposed the use of a skin delivery technology - the Nanopatch - to reduce both adjuvant and antigen dose but also retain its immune stimulating effects when compared to the conventional needle and syringe intramuscular (IM) delivery. We have demonstrated that Nanopatch delivery to skin requires only 1/100(th) of the IM antigen dose to induce equivalent humoral response. QS-21 enhanced humoral response in both skin and muscle route. Additionally, Nanopatch has demonstrated 30-fold adjuvant QS-21 dose sparing while retaining immune stimulating effects compared to IM. QS-21 induced localised, controlled cell death in the skin, suggesting that the danger signals released from dead cells contributed to the enhanced immunogenicity. Taken together, these findings demonstrated the suitability of reduced dose of QS-21 and the antigen using the Nanopatch to enhance humoral responses, and the potential to increase patient acceptability of QS-21 adjuvant. PMID:27404789

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

    International Nuclear Information System (INIS)

    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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Martins, Karen A O; Cooper, Christopher L; Stronsky, Sabrina M; Norris, Sarah L W; Kwilas, Steven A; Steffens, Jesse T; Benko, Jacqueline G; van Tongeren, Sean A; Bavari, Sina

    2016-01-01

    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. PMID:26870818

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

    Science.gov (United States)

    Martins, Karen A.O.; Cooper, Christopher L.; Stronsky, Sabrina M.; Norris, Sarah L.W.; Kwilas, Steven A.; Steffens, Jesse T.; Benko, Jacqueline G.; van Tongeren, Sean A.; Bavari, Sina

    2015-01-01

    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. PMID:26870818

  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

    2016-01-01

    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, 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. PMID:27515230

  20. Novel adjuvant Alum-TLR7 significantly potentiates immune response to glycoconjugate vaccines

    Science.gov (United States)

    Buonsanti, Cecilia; Balocchi, Cristiana; Harfouche, Carole; Corrente, Federica; Galli Stampino, Luisa; Mancini, Francesca; Tontini, Marta; Malyala, Padma; Bufali, Simone; Baudner, Barbara; De Gregorio, Ennio; Valiante, Nicholas M.; O’Hagan, Derek T.; Rappuoli, Rino; D’Oro, Ugo

    2016-01-01

    Although glycoconjugate vaccines are generally very efficacious, there is still a need to improve their efficacy, especially in eliciting a strong primary antibody response. We have recently described a new type of vaccine adjuvant based on a TLR7 agonist adsorbed to alum (Alum-TLR7), which is highly efficacious at enhancing immunogenicity of protein based vaccines. Since no adjuvant has been shown to potentiate the immune response to glycoconjugate vaccines in humans, we investigated if Alum-TLR7 is able to improve immunogenicity of this class of vaccines. We found that in a mouse model Alum-TLR7 greatly improved potency of a CRM197-MenC vaccine increasing anti-MenC antibody titers and serum bactericidal activity (SBA) against MenC compared to alum adjuvanted vaccine, especially with a low dose of antigen and already after a single immunization. Alum-TLR7 also drives antibody response towards Th1 isotypes. This adjuvant was also able to increase immunogenicity of all polysaccharides of a multicomponent glycoconjugate vaccine CRM197-MenACWY. Furthermore, we found that Alum-TLR7 increases anti-polysaccharide immune response even in the presence of a prior immune response against the carrier protein. Finally, we demonstrate that Alum-TLR7 adjuvant effect requires a functional TLR7. Taken together, our data support the use of Alum-TLR7 as adjuvant for glycoconjugate vaccines. PMID:27439378

  1. 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.

  2. Attenuation of antigenic immunogenicity by kynurenine, a novel suppressive adjuvant.

    Science.gov (United States)

    Duan, Zhiqing; Duan, Yunqing; Lei, Huangui; Hu, Ningzhu; Shi, Jiandong; Shen, Dong; Wang, Xi; Hu, Yunzhang

    2014-01-01

    A novel therapeutic strategy is required for autoimmune diseases characterized by the production of autoantibody, because current clinical strategies have limitations. Vaccination against autoimmune diseases is a feasible strategy because vaccines induce immune response memory and the antigen specificity. However, no suitable adjuvant is available to direct the immune response toward tolerance or suppression. In the current study, we evaluated whether kynurenine (Kyn) could serve as a novel suppressive adjuvant to decrease the humoral immune responses against hepatitis A virus (HAV) in the ICR mouse model in vivo and lipopolysaccharide (LPS) in B cells in vitro. The underlying mechanisms of Kyn-mediated suppression of LPS-induced IgM responses were explored. The results showed that Kyn significantly decreased HAV immunogenicity when co-administered with HAV, and that Kyn (100 μM/1000 μM) impaired IgM generation compared with that induced by LPS alone. We also demonstrated that microRNA30b (miR30b) played a critical role in the process of Kyn-mediated suppression of IgM responses induced by LPS, and that Bach2, a transcriptional repressor of B cell terminal differentiation, was a novel target of miR30b. These findings suggest that Kyn can serve as a novel and effective suppressive adjuvant for vaccines. PMID:24583631

  3. Immune responses to Mycoplasma bovis proteins formulated with different adjuvants.

    Science.gov (United States)

    Prysliak, Tracy; Perez-Casal, Jose

    2016-06-01

    Most vaccines for protection against Mycoplasma bovis disease are made of bacterins, and they offer varying degrees of protection. Our focus is on the development of a subunit-based protective vaccine, and to that end, we have identified 10 novel vaccine candidates. After formulation of these candidates with TriAdj, an experimental tri-component novel vaccine adjuvant developed at VIDO-InterVac, we measured humoral and cell-mediated immune responses in vaccinated animals. In addition, we compared the immune responses after formulation with TriAdj with the responses measured in animals vaccinated with a mix of a commercial adjuvant (Emulsigen™) and 2 of the components of the TriAdj, namely polyinosinic:polycytidylic acid (poly I:C) and the cationic innate defense regulator (IDR) peptide 1002 (VQRWLIVWRIRK). In this latter trial, we detected significant IgG1 humoral immune responses to 8 out of 10 M. bovis proteins, and IgG2 responses to 7 out of 10 proteins. Thus, we concluded that the commercial adjuvant formulated with poly I:C and the IDR peptide 1002 is the best formulation for the experimental vaccine. PMID:27105454

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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

    , dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared...

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

    Science.gov (United States)

    Skrastina, Dace; Petrovskis, Ivars; Lieknina, Ilva; Bogans, Janis; Renhofa, Regina; Ose, Velta; Dishlers, Andris; Dekhtyar, Yuri; Pumpens, Paul

    2014-01-01

    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. PMID:25436773

  9. Systemic adjuvant therapies in renal cell carcinoma.

    Science.gov (United States)

    Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea

    2012-10-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216

  10. Systemic adjuvant therapies in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sebastiano Buti

    2012-10-01

    Full Text Available Renal cell carcinoma (RCC is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC.

  11. Comparison of adjuvant activity of N- and C-terminal domain of gp96 in a Her2-positive breast cancer model

    OpenAIRE

    Pakravan, Nafiseh; Hassan, Zuhair Mohammad

    2011-01-01

    It has been frequently reported that gp96 acts as a strong biologic adjuvant. Some studies have even investigated adjuvant activity of the gp96 C- or N-terminal domain. The controversy surrounding adjuvant activity of gp96 terminal domains prompted us to compare adjuvant activity of gp96 C- or N-terminal domain toward Her2/neu, as DNA vaccine in a Her2/neu-positive breast cancer model. To do so, mice were immunized with DNA vaccine consisting of transmembrane and extracellular domain (TM + EC...

  12. An adjuvanted respiratory syncytial virus fusion protein induces protection in aged BALB/c mice

    Directory of Open Access Journals (Sweden)

    Cherukuri Anu

    2012-10-01

    Full Text Available Abstract Background Respiratory Syncytial Virus (RSV causes significant disease in the elderly, in part, because immunosenescence impairs protective immune responses to infection in this population. Despite previous and current efforts, there is no RSV vaccine currently licensed in infants or elderly adults. Adjuvanted RSV subunit vaccines have the potential to boost waning immune responses and reduce the burden of RSV disease in the elderly population. Results We used an aged BALB/c mouse model to evaluate immune responses to RSV Fusion (F protein in the absence and presence of an alum adjuvant. We demonstrate that aged BALB/c mice immunized with alum-adjuvanted RSV F protein had significantly reduced lung viral titers at day 4 following challenge with wild-type (wt RSV. Serum neutralizing antibody titers measured on day 27 correlated with protection in both young and aged vaccinated mice, although the magnitude of antibody titers was lower in aged mice. Unlike young mice, in aged mice, alum-adjuvanted RSV F did not induce lung TH2-type cytokines or eosinophil infiltration compared to non-adjuvanted F protein following wt RSV challenge. Conclusion Our studies demonstrate that neutralizing anti-RSV antibody titers correlate with protection in both young and aged BALB/c mice vaccinated with RSV F protein vaccines. The F + alum formulation mediated greater protection compared to the non-adjuvanted F protein in both young and aged mice. However, while alum can boost F-specific antibody responses in aged mice, it does not completely overcome the reduced ability of a senescent immune system to respond to the RSV F antigen. Thus, our data suggest that a stronger adjuvant may be required for the prevention of RSV disease in immunosenescent populations, to achieve the appropriate balance of protective neutralizing antibodies and effective TH1-type cytokine response along with minimal lung immunopathology.

  13. Adjuvant endocrine and chemotherapy for early breast cancer

    International Nuclear Information System (INIS)

    Objective: Present the results of the 1995 World Overview which will be held in Oxford England two weeks before ASTRO. Discuss the interpretation and application of these results. Review current research topics on the use of adjuvant endocrine and chemotherapy for early breast cancer. The survival benefits from adjuvant chemotherapy in premenopausal women and adjuvant tamoxifen in postmenopausal women are well established. Each will reduce the annual odds of death by about 25% resulting in a 10 year survival difference of 8-10%. By the time of this presentation, the results of the 1995 Adjuvant Therapy Overview should be with 10+ years of follow-up, and if possible these will be summarized. Current efforts to improve on previous results are focused on the following areas: Optimal chemotherapy dose. Decreasing dose will compromise patient survival. It is not as certain that increasing dose will have as much impact in improving survival. The NSABP was unable to demonstrate an improvement in survival by modestly increasing the dose of cyclophosphamide alone. However, recent results of a Canadian study of CEF (cyclophosphamide, epidoxorubicin, and 5-fluorouracil) and an Intergroup trial of an intense 16 week polychemotherapy program keep alive the possibility that dose escalation is still a very important question. An NSABP trial evaluating even greater cyclophosphamide dose escalation, an Intergroup evaluation of different doxorubicin doses, and two Intergroup trials evaluating very high dose chemotherapy and bone marrow transplantation should provide definitive evidence regarding the importance of dose. Drug sequence. A study from Milan suggests that initial treatment with single agent doxorubicin followed by CMF will be superior to alternating doxorubicin and CMF. This has not been confirmed yet, and the reason for increased benefit from such a sequence is not entirely clear. This concept is being explored further in an Intergroup trial comparing four cycles of

  14. Does lipophilicity per se induce adjuvant effects?

    DEFF Research Database (Denmark)

    Hansen, Jitka Stilund; Larsen, Søren Thor; Poulsen, Lars K.;

    2007-01-01

    ) or on lung function parameters. Thus, MP did not possess irritant or inflammatory properties, which may be a precursive stimulus for adjuvant effects. Second, mice were exposed to aerosols of MP, 6 or 323 mg/m3, for 1 h followed by a 20-min low-dose ovalbumin (OVA) inhalation. OVA only and OVA + Al......Anthopogenically introduced substances and pollutants are suspected to promote sensitization and development of allergic airway diseases, that is, acting as adjuvants. Lipophilicity may serve as an immunological warning signal, promoting adjuvant effects. Whether the lipophilicity of an inhaled...... compound induces immunomodulatory effects was investigated in a murine inhalation model with the highly lipophilic methyl palmitate (MP) as model substance. First, studies of acute effects following a 1-h exposure of up to 348 mg/m3 MP showed no effects on cell composition in bronchoalveolar lavage (BAL...

  15. 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...

  16. 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.

  17. Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.

    Directory of Open Access Journals (Sweden)

    Zhenyu Jia

    Full Text Available It is difficult to construct a control group for trials of adjuvant therapy (Rx of prostate cancer after radical prostatectomy (RP due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.

  18. Effectiveness of spray adjuvants on reduction of spray drift

    Science.gov (United States)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Five new drift control adjuvants were sele...

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

    OpenAIRE

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

    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 a...

  20. A Nomogram for Predicting the Benefit of Adjuvant Cytokine-Induced Killer Cell Immunotherapy in Patients with Hepatocellular Carcinoma

    OpenAIRE

    Qiu-Zhong Pan; Qi-Jing Wang; Jia-Qiang Dan; Ke Pan; Yong-Qiang Li; Yao-Jun Zhang; Jing-Jing Zhao; De-Sheng Weng; Yan Tang; Li-Xi Huang; Jia He; Shi-Ping Chen; Miao-La Ke; Min-Shan Chen; Wicha, Max S.

    2015-01-01

    The benefits of adjuvant cytokine-induced killer (CIK) cell immunotherapy for hepatocellular carcinoma (HCC) remain mixed among patients. Here, we constructed a prognostic nomogram to enable individualized predictions of survival benefit of adjuvant CIK cell treatment for HCC patients. Survival analysis showed that the median overall survival (OS) and progression-free survival (PFS) for patients in the hepatectomy/CIK combination group were 41 and 16 months, respectively, compared to 28 and 1...

  1. 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.

  2. 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.

  3. 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. PMID:27449155

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

    Science.gov (United States)

    Bigaeva, Emilia; van Doorn, Eva; Liu, Heng; Hak, Eelko

    2016-01-01

    Background and Objectives 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. Methods 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. Results 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). Conclusions 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

  5. 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

  6. 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.

  7. 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

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

    OpenAIRE

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

    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.

  9. 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...

  10. 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

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

    International Nuclear Information System (INIS)

    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/m2 weekly) either before and after radiotherapy or only after radiotherapy. Twenty-two patients received concurrent full-dose Gem (1,000 mg/m2 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. 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.

  13. 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.

  14. 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.

  15. Adjuvant Therapy of Colon Cancer: Current Status and Future Developments

    OpenAIRE

    Morse, Michael A.

    2005-01-01

    Options for the adjuvant therapy of resected stage III colon cancer have expanded beyond the previously well-accepted standard of 5-fluorouracil (5-FU) combined with leucovorin. The Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) study confirmed that capecitabine (Xeloda) is at least as effective and is less toxic than a bolus 5-FU and leucovorin regimen for patients with stage III colon cancer. This study, in addition to National Surgical Adjuvant Breast and Bowel Project (NSABP) C-06, which...

  16. Adjuvant auricular electroacupuncture and autogenic training in rheumatoid arthritis: a randomized controlled trial. Auricular acupuncture and autogenic training in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Bernateck, M; Becker, M; Schwake, C;

    2008-01-01

    BACKGROUND: In contrast to psychological interventions the usefulness of acupuncture as an adjuvant therapy in rheumatoid arthritis (RA) has not yet been demonstrated. OBJECTIVE: The efficacy of auricular electroacupuncture (EA) was directly compared with autogenic training (AT). METHODS: Patients...

  17. [Recent advance in adjuvant therapy for breast cancer].

    Science.gov (United States)

    Shimizu, Chikako; Watanabe, Toru

    2002-12-01

    Adjuvant systemic therapy has contributed to a significant improvement of disease-free and overall survival in addition to surgery and irradiation to the local disease. The adjuvant therapy to a patient is determined integrating the information on estimated risk of recurrence, benefit and harm of the therapy and the patient's value. In this review, the state of the art of adjuvant therapy is discussed from several aspects, such as interpretation and evaluation of risk, the best available evidences on adjuvant systemic therapy, the future direction of primary therapy for breast cancer, and patient-oriented decision making. PMID:12506467

  18. CpG ODN and ISCOMATRIX Adjuvant: A Synergistic Adjuvant Combination Inducing Strong T-Cell IFN-γ Responses

    OpenAIRE

    Michael J. McCluskie; Weeratna, Risini D.; Evans, Dana M.; Shawn Makinen; Debbie Drane; Heather L. Davis

    2013-01-01

    For the induction of robust humoral and cellular immune responses, a strong rationale exists to use vaccine-adjuvant combinations possessing both immune modulatory and enhanced delivery capabilities. Herein, we evaluated the combination of 2 different adjuvants, a TLR9 agonist, composed of synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG), and ISCOMATRIX adjuvant (ISCOMATRIX), composed of saponin, phospholipid, and cholesterol, which possesses both immunostim...

  19. 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. PMID:20175969

  20. 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.

  1. Efficacy of chitosan oligosaccharide as aquatic adjuvant administrated with a formalin-inactivated Vibrio anguillarum vaccine.

    Science.gov (United States)

    Liu, Xiaohong; Zhang, Hua; Gao, Yuan; Zhang, Yang; Wu, Haizhen; Zhang, Yuanxing

    2015-12-01

    Vaccine is one of the efficient candidates to prevent fish disease through activating host immune response in aquaculture. Actually, several vaccines are often administered with adjuvants to increase immunostimulation, especially for some water-based formalin-killed vaccines. However, side effects are inevitable after vaccination of some adjuvants. Therefore, exploration for effective and harmless aquatic adjuvants is urgently needed. In this study, immunoprotection of a formalin-inactivated Vibrio anguillarum vaccine applied with chitosan oligosaccharide (COS) was analyzed. High levels of protection were achieved in zebrafish and turbot vaccinated with inactivated vaccine and COS (RPS of 89.0 ± 4.5% and 80.0 ± 6.9%) compared with fish vaccinated with inactivated vaccine alone (RPS of 47.8 ± 6.6% and 64.7 ± 5.8%) at 4 week post vaccination. Moreover, high antibody reaction and cross-protection against Vibrio alginolyticus and Vibrio harveyi were observed of turbot vaccinated with inactivated vaccine and COS. In conclusion, COS can enhance immunoprotection of a formalin-inactivated V. anguillarum vaccine, significantly activate humoral immune response of host, and be benefit for inhibition against pathogens. Therefore, COS would be a potential adjuvant for aquatic vaccine design in the future. PMID:26476108

  2. 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.

  3. 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.

  4. 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. PMID:27342914

  5. Effective polymer adjuvants for sustained delivery of protein subunit vaccines.

    Science.gov (United States)

    Adams, Justin R; Haughney, Shannon L; Mallapragada, Surya K

    2015-03-01

    We have synthesized thermogelling cationic amphiphilic pentablock copolymers that have the potential to act as injectable vaccine carriers and adjuvants that can simultaneously provide sustained delivery and enhance the immunogenicity of released antigen. While these pentablock copolymers have shown efficacy in DNA delivery in past studies, the ability to deliver both DNA and protein for subunit vaccines using the same polymeric carrier can provide greater flexibility and efficacy. We demonstrate the ability of these pentablock copolymers, and the parent triblock Pluronic copolymers to slowly release structurally intact and antigenically stable protein antigens in vitro, create an antigen depot through long-term injection-site persistence and enhance the in vivo immune response to these antigens. We show release of the model protein antigen ovalbumin in vitro from the thermogelling block copolymers with the primary, secondary and tertiary structures of the released protein unchanged compared to the native protein, and its antigenicity preserved upon release. The block copolymers form a gel at physiological temperatures that serves as an antigenic depot and persists in vivo at the site of injection for over 50days. The pentablock copolymers show a significant fivefold enhancement in the immune response compared to soluble protein alone, even 6weeks after the administration, based on measurement of antibody titers. These results demonstrate the potential of these block copolymers hydrogels to persist for several weeks and sustain the release of antigen with minimal effects on protein stability and antigenicity; and their ability to be used simultaneously as a sustained delivery device as well as a subunit vaccine adjuvant platform. PMID:25484331

  6. 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.

  7. Adjuvant Bidirectional Chemotherapy Using an Intraperitoneal Port

    Directory of Open Access Journals (Sweden)

    Paul H. Sugarbaker

    2012-01-01

    Full Text Available Cytoreductive surgery (CRS and hyperthermic intraperitoneal chemotherapy (HIPEC have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement.

  8. Adjuvant chemotherapy for soft tissue sarcoma.

    Science.gov (United States)

    Casali, Paolo G

    2015-01-01

    Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence. PMID:25993233

  9. 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. PMID:9554254

  10. 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.

  11. Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer.

    Science.gov (United States)

    Mallmann, Peter; Mallmann, Christoph

    2016-01-01

    Neoadjuvant chemotherapy is indicated in patients who can tolerate the side effects of a chemotherapy and with preoperative presentation of one of the following clinical risk situations: bulky disease with a maximal tumor diameter of > 4 cm, suspicious lymph nodes in magnetic resonance imaging (MRI), computed tomography (CT) scan or endosonography, histopathologically confirmed lymph node metastasis, or histopathologically documented risk factors such as G3 and L1V1. A neoadjuvant chemotherapy followed by surgery should be performed with cisplatin at a dosage of > 25 mg/m2 per week and an application interval of < 14 days. The previously published data suggests an improved rate of complete resection and reduced incidences of positive lymph nodes and parametric infiltration. Accordingly, the percentage of patients in need for adjuvant radiochemotherapy after operation can be significantly reduced. Some studies demonstrated a prolongation of progression-free and overall survival. Following the previously published studies, adjuvant chemotherapy after operation or after radiochemotherapy has no significant effect on the overall survival and, following the current guidelines, should be avoided. PMID:27614740

  12. 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.

  13. 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...

  14. 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...

  15. 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

  16. Evaluation of adjuvant chemoradiation therapy for ampullary adenocarcinoma: the Johns Hopkins Hospital - Mayo Clinic collaborative study

    International Nuclear Information System (INIS)

    The role of adjuvant chemoradiation therapy for ampullary carcinoma is unknown. Previous literature suggests that certain populations with high risk factors for recurrence may benefit from adjuvant chemoradiation. We combined the experience of two institutions to better delineate which patients may benefit from adjuvant chemoradiation. Patients who underwent curative surgery for ampullary carcinoma at the Johns Hopkins Hospital (n = 290; 1992-2007) and at the Mayo Clinic (n = 130; 1977-2005) were reviewed. Patients with <60 days of follow-up, metastatic disease at surgery, or insufficient pathologic data were excluded. The final combined study consisted of 186 patients (n = 104 Johns Hopkins, n = 82 Mayo). Most patients received 5-FU based chemoradiation with conformal radiation. Cox proportional hazards models were used for survival analysis. Median overall-survival was 39.9 months with 2- and 5-year survival rates of 62.4% and 39.1%. On univariate analysis, adverse prognostic factors for overall survival included T3/T4 stage disease (RR = 1.86, p = 0.002), node positive status (RR = 3.18, p < 0.001), and poor histological grade (RR = 1.69, p = 0.011). Patients who received adjuvant chemoradiation (n = 66) vs. surgery alone (n = 120) showed a higher rate of T3/T4 stage disease (57.6% vs. 30.8%, P < 0.001), lymph node involvement (72.7% vs. 30.0%, P < 0.001), and close or positive margins (4.6% vs. 0.0%, P = 0.019). Five year survival rates among node negative and node positive patients were 58.7% and 18.4% respectively. When compared with surgery alone, use of adjuvant chemoradiation improved survival among node positive patients (mOS 32.1 vs. 15.7 mos, 5 yr OS: 27.5% vs. 5.9%; RR = 0.47, P = 0.004). After adjusting for adverse prognostic factors on multivariate analysis, patients treated with adjuvant chemoradiation demonstrated a significant survival benefit (RR = 0.40, P < 0.001). Disease relapse occurred in 37.1% of all patients, most commonly metastatic

  17. 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.

  18. The Divergent CD8+ T Cell Adjuvant Properties of LT-IIb and LT-IIc, Two Type II Heat-Labile Enterotoxins, Are Conferred by Their Ganglioside-Binding B Subunits.

    Directory of Open Access Journals (Sweden)

    John C Hu

    Full Text Available Poor immune responses elicited by vaccine antigens can be enhanced by the use of appropriate adjuvants. Type II heat-labile enterotoxins (HLT produced by Escherichia coli are extremely potent adjuvants that augment both humoral and cellular immunity to co-administered antigens. Recent findings demonstrate that LT-IIb and LT-IIc, two type II HLT adjuvants, exhibit potent, yet distinguishable CD8(+ T cell adjuvant properties. While LT-IIc elicits a robust and rapid response at one week after administration, LT-IIb engenders a more gradual and slower expansion of antigen-specific CD8(+ T cells that correlates with improved immunity. The variations in immune effects elicited by the HLT adjuvants have been generally attributed to their highly divergent B subunits that mediate binding to various gangliosides on cell surfaces. Yet, HLT adjuvants with point mutations in the B subunit that significantly alter ganglioside binding retain similar adjuvant functions. Therefore, the contribution of the B subunits to adjuvanticity remains unclear. To investigate the influence of the B subunits on the enhancement of immune responses by LT-IIb and LT-IIc, chimeric HLT were engineered in which the B subunits of the two adjuvants were exchanged. Comparing the immune potentiating characteristics of both native and chimeric HLT adjuvants, it was found that not all the adjuvant characteristics of the HLT adjuvants were modulated by the respective B subunits. Specifically, the differences in the CD8(+ T cell kinetics and protective responses elicited by LT-IIb and LT-IIc did indeed followed their respective B subunits. However, induction of IL-1 from macrophages and the capacity to intoxicate cells in a mouse Y1 adrenal cell bioassay did not correlate with the B subunits. Therefore, it is likely that additional factors other than the B subunits contribute to the effects elicited by the HLT adjuvants.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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. PMID:26973069

  4. 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. PMID:27219467

  5. 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...

  6. Comparative study on effect of poly glycosides of Tripterygium wilfordii Hook on morphology of testicles and expression of NOS in normal and adjuvant-induced arthritis rats%雷公藤多苷对正常及佐剂关节炎大鼠睾丸组织形态结构、NOS表达影响的比较研究

    Institute of Scientific and Technical Information of China (English)

    李健; 谭勇; 吕永恒; 何小鹃; 鞠大宏; 吕爱平

    2011-01-01

    Objective: Comparative study on the differences of male reproductive toxicity disturbed by Tripterygium Wilfordii Multiglycoside (GTW) in normal rats and adjuvant induced arthritic rats (AA rat). Methods: male SD rats were randomly divided into two groups, normal group and AA group. GTW 0, 7, 70 and 105 mg·kg-1 day-1 was given to rats intragastrically for two weeks. After that, all animals were sacrificed, the testicle and epididymal coefficient were calculated, histopathological changes of testis was observed by H&E and NOS antibody immunohistochemical procedure,and the NOS level in testicle tissue was tested by chemical colorimetric method. Results: The changes were not detected both in normal group and AA group treated by 7mg·kg-1 GTW (clinical equal effective dosage). 70 mg·kg-1 GTW can induce testis toxicity in normal rats. However, none adverse impacts were observed in AA rats. 105 mg· kg-1 GTW can arouse significant testis toxicity both in normal rats and AA rats. Conclusion: There is the dose-related feature on testis toxicity of GTW. On the other side, the testis toxicity is relative to physiological status. The same dosage GTW can rouse weak testis toxicity in AA rats than that in normal rats.%目的:比较雷公藤多苷(GTW)时正常大鼠及佐剂关节炎雄性大鼠生殖毒性的差异.方法:雄性SD大鼠随机分为2姐:正常组及弗氏完全佐剂诱导的关节炎组(每组60只).各组大鼠同时以CTW灌胃,剂量分别为:0、7、70及105mg/kg/d,给药2用后取材,测量睾丸及附睾系数,检测睾丸组织中NOS含量及分布,观察睾丸组织病理变化.结果:105mg/kg GTW对正常及关节炎大鼠均能诱发生殖毒性;70mg/kg GTW可诱发正常大鼠生殖毒性,而该剂量GTW对关节炎大鼠没有明显的生殖毒性;7mg/kgGVW则对正常及关节炎大鼠均无生殖毒性.结论:GTW的睾丸毒性除与剂量相关外,与机体生理状态关联,相同剂量GTW在关节支动物体内产生的睾丸毒性较正常动物弱.

  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. The Adjuvant Activity of Epimedium Polysaccharide-Propolis Flavone Liposome on Enhancing Immune Responses to Inactivated Porcine Circovirus Vaccine in Mice

    OpenAIRE

    Yunpeng Fan; Liwei Guo; Weifeng Hou; Chao Guo; Weimin Zhang; Xia Ma; Lin Ma; Xiaoping Song

    2015-01-01

    Objectives. The adjuvant activity of Epimedium polysaccharide-propolis flavone liposome (EPL) was investigated in vitro and in vivo. Methods. In vitro, the effects of EPL at different concentrations on splenic lymphocytes proliferation and mRNA expression of IFN-γ and IL-6 were determined. In vivo, the adjuvant activities of EPL, EP, and mineral oil were compared in BALB/c mice through vaccination with inactivated porcine circovirus type 2 (PCV2) vaccine. Results. In vitro, EPL promoted lymph...

  9. 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....

  10. Quadrantectomy and adjuvant radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    The conservative treatment of early breast cancer always requires irradiation of residual mammary tissue. The preliminary results obtained in 45 early breast cancer patients, who received quadrantectomy plus axillary dissection, followed by radiation of residual breast are reported. Radiation was performed by the two opposed field technique. In some cases the residual breast tissue was compressed using a special accessory provided with the Theratron 780. In addition to the tumor dose of 50 GY, 10 GY boots was added to the surgical scar using 7 MeV electrons. The 6 patients with positive axillary nodes received 6 courses of adjuvant chemotherapy (CMF) after radiotherapy. All patients are currently alive and free of disease. The 64% (29 patients) were followed up for at least 5 years, and 36% (16 patients) for at least 3 years. Only 2 cases of local recurrence were encountered (4,4%). The esthetic result was satisfactory in all cases. No side effects due to treatment were noted

  11. Results of combination treatment using docetaxel in an adjuvant chemotherapy regimen for resectable breast cancer

    OpenAIRE

    L. V. Bolotina; T. I. Deshkina

    2014-01-01

    Breast cancer (BC) dominates in the structure of cancer morbidity and mortality in women worldwide. Despite the advances made in the treatment of this pathology, there is still a variety of unsolved problems, including those associated with disease progression after radical sur- gical interventions. One of the urgent current tasks is to estimate the adequate volume of adjuvant treatment with regard to the biological features of a tumor. Our investigation comparatively analyzed the efficiency ...

  12. Xanthan Gum as an Adjuvant in a Subunit Vaccine Preparation against Leptospirosis

    OpenAIRE

    Bacelo, Katia L.; Hartwig, Daiane D.; Seixas, Fabiana K.; Rodrigo Schuch; Angelita da S. Moreira; Marta Amaral; Tiago Collares; Vendrusculo, Claire T.; McBride, Alan J. A.; Dellagostin, Odir A.

    2014-01-01

    Leptospiral immunoglobulin-like (Lig) proteins are of great interest due to their ability to act as mediators of pathogenesis, serodiagnostic antigens, and immunogens. Purified recombinant LigA protein is the most promising subunit vaccine candidate against leptospirosis reported to date, however, as purified proteins are weak immunogens the use of a potent adjuvant is essential for the success of LigA as a subunit vaccine. In the present study, we compared xanthan pv. pruni (strain 106), alu...

  13. 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.

  14. The effects of adjuvants on CTL induction by V3:Ty-virus-like particles (V3-VLPs) in mice.

    Science.gov (United States)

    Harris, S J; Woodrow, S A; Gearing, A J; Adams, S E; Kingsman, A J; Layton, G T

    1996-07-01

    We have previously described the generation of HIV-1 V3-specific cytotoxic T-lymphocytes (CTL) responses in BALB/c (H-2d) mice following immunization with Ty-virus-like particles carrying the V3 loop of gp120 (V3-VLPs) without adjuvant. In this study the effects of various adjuvants on CTL induction by V3-VLPs was examined. Mice immunized with V3-VLPs formulated in aqueous-based adjuvants, Detox, gamma-inulin, galactosaminylmuramyl dipeptide and Chemivax generated V3-specific CTL responses, although at reduced levels when compared to the no adjuvant group. V3-VLPs prepared in Alhydrogel, algamulin or as an oil emulsion in SAF-MF failed to generate V3-specific CTL responses. The mechanism whereby alum prevented the induction of a CTL response was investigated further. Immunization with V3-VLPs prepared in non-saturating doses of alum or alum plus EDTA primed for strong CTL responses, indicating that free VLPs do, but alum-bound VLPs do not enter the MHC class I processing pathway of antigen-presenting cells (APCs). Furthermore, V3-VLPs with very low doses of alum led to an enhancement of the CTL response. The formulation of hybrid Ty-VLPs in oil based or precipitating adjuvants, therefore, inhibits access to the MHC class I processing pathway of APCs. The intact particulate structure of hybrid VLPs is therefore strictly necessary for CTL induction. PMID:8873390

  15. 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.

  16. 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.

  17. Adjuvant radiation for vulvar carcinoma: improved local control

    International Nuclear Information System (INIS)

    Purpose: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. Methods and Materials: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. Results: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). Conclusion: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and

  18. Mechanism of the adjuvant activity of the synthetic mycobacterial cord factor analog Trehalose-6,6-dibehenate (TDB)

    OpenAIRE

    Althaus, Kerstin

    2010-01-01

    The mechanism behind the adjuvant activity of the mycobacterial cord factor TDM and its synthetic analog TDB as a component of the new adjuvant system CAF01 was investigated and compared to the TLR9 ligand CpG. In vitro, TDB and TDM potently activate antigen-presenting cells via a Myd88 and TLR independent, but FcRg-Syk-Card9 dependent signaling pathway. Microarray analysis indicated that in macrophages, TDB induced genome-wide transcriptional responses similar to the Dectin-1 ligand Curdlan ...

  19. 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.

  20. CpG ODN and ISCOMATRIX Adjuvant: A Synergistic Adjuvant Combination Inducing Strong T-Cell IFN-γ Responses

    Directory of Open Access Journals (Sweden)

    Michael J. McCluskie

    2013-01-01

    Full Text Available For the induction of robust humoral and cellular immune responses, a strong rationale exists to use vaccine-adjuvant combinations possessing both immune modulatory and enhanced delivery capabilities. Herein, we evaluated the combination of 2 different adjuvants, a TLR9 agonist, composed of synthetic oligodeoxynucleotides (ODN containing immunostimulatory CpG motifs (CpG, and ISCOMATRIX adjuvant (ISCOMATRIX, composed of saponin, phospholipid, and cholesterol, which possesses both immunostimulatory and delivery properties. While both individual adjuvants have been shown effective in numerous preclinical and clinical studies, it is likely that for optimal adjuvant activity a combined adjuvant approach will be necessary. Herein, using three different antigens, namely, hepatitis B surface antigen (HBsAg, ovalbumin (OVA, and influenza A haemagglutinin antigen (HA, we show in mice that some adjuvant effects of CpG and ISCOMATRIX are further enhanced if they are used in combination. In particular, with all three antigens, IFN-γ levels were greatly increased with the CpG/ISCOMATRIX combination. The ability of the CpG/ISCOMATRIX combination to induce antitumor responses when administered with OVA following administration to mice of a highly metastatic OVA-secreting tumor cell line (B16-OVA melanoma was also demonstrated. Thus the CpG/ISCOMATRIX combination may prove to be a valuable tool in the development of novel or improved vaccines.

  1. Adjuvant chemotherapy after liver transplanta-tion for hepatocellular carcinoma:a systematic review and a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Hua-Shan Lin; Ren-Hua Wan; Liang-Hui Gao; Jian-Feng Li; Ren-Feng Shan; Jun Shi

    2015-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide and liver transplanta-tion (LT) is considered as the best therapeutic option for patients with HCC combined with cirrhosis. However, tumor recurrence after LT for HCC remains the major obstacle for long-term survival. The present study was to evaluate the efif-cacy and necessity of adjuvant chemotherapy in patients with HCC who had undergone LT. DATA SOURCES: Several databases were searched to identify comparative studies fuliflling the predeifned selection criteria before October 2014. Suitable studies were chosen and data extracted for meta-analysis. Three authors independently evaluated the bias of each study according to the Cochrane Handbook for Systematic Review of Intervention. Stata 12 was used for statistical analysis. Hazard ratio (HR) was considered as a summary statistic for overall survival, disease-free survival and recurrence rate. RESULTS: Three prospective studies and 5 retrospective stud-ies including 360 patients (166 in the adjuvant chemotherapy group, and 194 in the control group) were included. Com-pared with the control group, post-LT adjuvant chemotherapy conferred signiifcant beneift for overall survival (HR: 0.34;95% CI: 0.22-0.52;P=0.000). Meanwhile, the results showed an improvement for disease-free survival on favoring adju-vant chemotherapy (HR: 0.87; 95% CI: 0.78-0.95;P=0.004). However, no signiifcant difference in HCC recurrence rate was observed between the two groups (HR: 1.26; 95% CI: 0.40-4.00;P=0.696). Descriptions of adverse events were of anecdotal na-ture and did not allow meta-analytic calculations. CONCLUSIONS: Adjuvant chemotherapy after LT for HCC can signiifcantly prolong patient's survival and delay the recurrence of HCC. For advanced HCC with poor differentia-tion, patients may perhaps beneift from the early implantation of adjuvant chemotherapy after LT.

  2. 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...

  3. Influence of radiotherapy on the dose of adjuvant chemotherapy in early breast cancer

    International Nuclear Information System (INIS)

    399 patients with early breast cancer were randomly allocated to treatment by either modified radical mastectomy or lumpectomty and radiotherapy. 169 had histologically involved axillary nodes and were randomised to receive either adjuvant cytotoxic chemotherapy (76 patients) or no systemic adjuvant treatment (93 patients). Chemotherapy comprised a combination of oral cyclophosphamide and intravenous methotrexate and 5-fluorouracil (CMF) for 12 cycles over one year. Patients in the mastectomy group received a significantly higher percentage of the planned chemotherapy dose compared with those in the radiotherapy group (median 85% v. 71% p < 0.05). Patients treated with radiotherapy were more frequently nauseated and developed more severe alopecia, but these differences were not statistically significant. At median follow-up of 37 months the relapse-rate and pattern of relapse were similar in both groups of patients receiving CMF. (author). 11 refs.; 5 tabs

  4. 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.

  5. Xanthan Gum as an Adjuvant in a Subunit Vaccine Preparation against Leptospirosis

    Directory of Open Access Journals (Sweden)

    Katia L. Bacelo

    2014-01-01

    Full Text Available Leptospiral immunoglobulin-like (Lig proteins are of great interest due to their ability to act as mediators of pathogenesis, serodiagnostic antigens, and immunogens. Purified recombinant LigA protein is the most promising subunit vaccine candidate against leptospirosis reported to date, however, as purified proteins are weak immunogens the use of a potent adjuvant is essential for the success of LigA as a subunit vaccine. In the present study, we compared xanthan pv. pruni (strain 106, aluminium hydroxide (alhydrogel, and CpG ODN as adjuvants in a LigA subunit vaccine preparation. Xanthan gum is a high molecular weight extracellular polysaccharide produced by fermentation of Xanthomonas spp., a plant-pathogenic bacterium genus. Preparations containing xanthan induced a strong antibody response comparable to that observed when alhydrogel was used. Upon challenge with a virulent strain of L. interrogans serovar Copenhageni, significant protection (Fisher test, P<0.05 was observed in 100%, 100%, and 67% of hamsters immunized with rLigANI-xanthan, LigA-CpG-xanthan, and rLigANI-alhydrogel, respectively. Furthermore, xanthan did not cause cytotoxicity in Chinese hamster ovary (CHO cells in vitro. The use of xanthan as an adjuvant is a novel alternative for enhancing the immunogenicity of vaccines against leptospirosis and possibly against other pathogens.

  6. Effects of Adjuvant Analgesics on Cerebral Ischemia-Induced Mechanical Allodynia.

    Science.gov (United States)

    Matsuura, Wataru; Harada, Shinichi; Tokuyama, Shogo

    2016-01-01

    Central post-stroke pain (CPSP), a potential sequela of stroke, is classified as neuropathic pain. Although we recently established a CPSP-like model in mice, the effects of adjuvant analgesics as therapeutic drugs for neuropathic pain in this model are unknown. Hence, the aim of the present study was to assess the usefulness of our model by evaluating the effects of adjuvant analgesics used for treating neuropathic pain in this mouse model of CPSP. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). The development of hind paw mechanical allodynia was measured after BCAO using the von Frey test. The mechanical allodynia was significantly increased on day 3 after BCAO compared with that during the pre-BCAO assessment. BCAO-induced mechanical allodynia was significantly decreased by intraperitoneal injections of imipramine (a tricyclic antidepressant), mexiletine (an antiarrhythmic), gabapentin (an antiepileptic), or a subcutaneous injection of morphine (an opioid receptor agonist) compared with that following vehicle treatment in BCAO-mice. By contrast, milnacipran (a serotonin and norepinephrine reuptake inhibitor), paroxetine (selective serotonin reuptake inhibitor), carbamazepine (antiepileptic), and indomethacin (nonsteroidal anti-inflammatory drug) did not affect the BCAO-induced mechanical allodynia. Our results show that BCAO in mice may be useful as an animal model of CPSP. In addition, BCAO-induced mechanical allodynia may be suppressed by some adjuvant analgesics used to treat neuropathic pain. PMID:27150152

  7. 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.

  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. Advances in aluminum hydroxide-based adjuvant research and its mechanism

    OpenAIRE

    He, Peng; Zou, Yening; Hu, Zhongyu

    2015-01-01

    In the past few decades, hundreds of materials have been tried as adjuvant; however, only aluminum-based adjuvants continue to be used widely in the world. Aluminum hydroxide, aluminum phosphate and alum constitute the main forms of aluminum used as adjuvants. Among these, aluminum hydroxide is the most commonly used chemical as adjuvant. In spite of its wide spread use, surprisingly, the mechanism of how aluminum hydroxide-based adjuvants exert their beneficial effects is still not fully und...

  10. 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)....

  11. Patient adherence to aromatase inhibitor treatment in the adjuvant setting

    OpenAIRE

    Verma, S.; Madarnas, Y.; Sehdev, S.; Martin, G; Bajcar, J.

    2011-01-01

    Improvements in adjuvant systemic therapy and detection of early disease have resulted in a decline of breast cancer death rates across all patient age groups in Canada. Non-adherence to adjuvant hormonal therapy in the setting of early breast cancer may significantly affect patient outcome. Factors associated with medication adherence are complex and may be patient-related, therapy-related, and health care provider–related. To date, there is a gap in the literature concerning a comprehensive...

  12. Second malignancies after breast cancer: The impact of adjuvant therapy

    OpenAIRE

    Dong, Chunhui; Chen, Ling

    2014-01-01

    Second malignant neoplasms (SMNs) are potentially life-threatening late sequelae of the adjuvant therapy for breast cancer (BC). The increased risk of SMNs is associated with adjuvant chemotherapy (development of secondary acute myeloid leukemia and myelodysplastic syndrome) and hormonal therapy (risk of uterine cancer secondary to tamoxifen treatment). Previous studies have demonstrated an increased risk of SMNs associated with alkylating agents, topoisomerase-II inhibitors, granulocyte-stim...

  13. Experimental study on Cervi Cornu on Adjuvant Arthritis in rats

    OpenAIRE

    Ji-Won, Shin; Jai-Young, Park; Hee-Soo,Park

    2002-01-01

    Objective: To investigate effects of Cervi Cornu on Adjuvant Athritis in rats, the edema inhibit rate, the anaJgesic effects, the number of WBC, RA facter, Platelet, the quantity of CRP, total protein, albumin and globuline in the blood serum were measured in the arthritis part. Results: The results obtained as fonows ; 1. After arthritis of Sprague dawley(SD) rats was induced by injecting Freund's complete adjuvant for 2 weeks, any treatment was not for Control group, acupunctured for Tr...

  14. 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

  15. 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.

  16. Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

    International Nuclear Information System (INIS)

    Purpose: Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Methods and Materials: Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA–IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. Results: We identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I–IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB–C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651–1.002, p = 0.052) Conclusion: In FIGO Stage IB–C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival.

  17. Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Anne, E-mail: akim2@health-quest.org [Department of Radiation Oncology, Vassar Brothers Medical Center, Poughkeepsie, NY (United States); Schreiber, David [Department of Veterans Affairs, New York Harbor Healthcare System, Brooklyn, NY (United States); Rineer, Justin [Department of Radiation Oncology, MD Anderson Cancer Center Orlando, Orlando, FL (United States); Choi, Kwang; Rotman, Marvin [Department of Radiation Oncology, SUNY Downstate Medical Center, Brooklyn, NY (United States)

    2011-11-15

    Purpose: Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Methods and Materials: Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA-IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. Results: We identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I-IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB-C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651-1.002, p = 0.052) Conclusion: In FIGO Stage IB-C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival.

  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. 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

  20. 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.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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

  3. 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.

  4. Characterization of a mutant Escherichia coli heat-labile toxin, LT(R192G/L211A), as a safe and effective oral adjuvant.

    Science.gov (United States)

    Norton, Elizabeth B; Lawson, Louise B; Freytag, Lucy C; Clements, John D

    2011-04-01

    Despite the fact that the adjuvant properties of the heat-labile enterotoxins of Escherichia coli (LT) and Vibrio cholerae (CT) have been known for more than 20 years, there are no available oral vaccines containing these molecules as adjuvants, primarily because they are both very potent enterotoxins. A number of attempts with various degrees of success have been made to reduce or eliminate the enterotoxicity of LT and CT so they can safely be used as oral adjuvants or immunogens. In this report we characterize the structural, enzymatic, enterotoxic, and adjuvant properties of a novel mutant of LT, designated LT(R192G/L211A), or dmLT. dmLT was not sensitive to trypsin activation, had reduced enzymatic activity for induction of cyclic AMP in Caco-2 cells, and exhibited no enterotoxicity in the patent mouse assay. Importantly, dmLT retained the ability to function as an oral adjuvant for a coadministered antigen (tetanus toxoid) and to elicit anti-LT antibodies. In vitro and in vivo data suggest that the reduced enterotoxicity of this molecule compared to native LT or the single mutant, LT(R192G), is a consequence of increased sensitivity to proteolysis and rapid intracellular degradation in mammalian cells. In conclusion, dmLT is a safe and powerful detoxified enterotoxin with the potential to function as a mucosal adjuvant for coadministered antigens and to elicit anti-LT antibodies without undesirable side effects. PMID:21288994

  5. Adjuvant and anti-inflammatory properties of cigarette smoke in murine allergic airway inflammation.

    Science.gov (United States)

    Trimble, Nancy J; Botelho, Fernando M; Bauer, Carla M T; Fattouh, Ramzi; Stämpfli, Martin R

    2009-01-01

    The impact of cigarette smoke on allergic asthma remains controversial both clinically and experimentally. The objective of this study was to investigate, in a murine model, how cigarette smoke affects immune inflammatory processes elicited by a surrogate allergen. In our experimental design, mice were concurrently exposed to cigarette smoke and ovalbumin (OVA), an innocuous antigen that, unless introduced in the context of an adjuvant, induces inhalation tolerance. We show that cigarette smoke exposure has adjuvant properties, allowing for allergic mucosal sensitization to OVA. Specifically, concurrent exposure to cigarette smoke and OVA for 2 weeks led to airway eosinophilia and goblet cell hyperplasia. In vivo OVA recall challenge 1 month after the last smoke exposure showed that concurrent exposure to OVA and cigarette smoke induced antigen-specific memory. Robust eosinophilia and OVA-specific IgG1 and IgE characterized the ensuing inflammatory response. Mechanistically, allergic sensitization was, in part, granulocyte macrophage colony-stimulating factor (GM-CSF) dependent, as a significant reduction in BAL eosinophilia was observed in mice treated with an anti-GM-CSF antibody. Of note, continuous smoke exposure attenuated the OVA recall response; decreased airway eosinophilia was observed in mice continuously exposed to cigarette smoke compared with mice that ceased the smoke exposure protocol. In conclusion, we demonstrate experimentally that while cigarette smoke acts as an adjuvant allowing for allergic sensitization, it also attenuates the ensuing eosinophilic inflammatory response. PMID:18635815

  6. 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.

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. Excellent outcomes with adjuvant toremifene or tamoxifen in early stage breast cancer

    Directory of Open Access Journals (Sweden)

    Jaime D. Lewis

    2014-01-01

    Full Text Available Fareston (toremifene and tamoxifen, both selective estrogen receptor modulators, are therapeutically equivalent treatments for metastatic breast cancer. We hypothesized that toremifene as compared with tamoxifen given as adjuvant therapy for early stage breast cancer would result in equivalent survival with an improved side effect profile, therefore, providing superior therapeutic efficacy.Subjects and methods. The North American Fareston versus Tamoxifen Adjuvant trial assigned 1813 perimenopausal or postmenopausal women with hormone receptor (HR – positive invasive breast cancer to adjuvant treatment with either tamoxifen or toremifene. The primary outcomes evaluated were disease-free survival (DFS and overall survival (OS.Results. Median follow-up was 59 months. The baseline characteristics of the 2 treatment groups were well-balanced. On the basis of intenttotreat, 5-year actuarial DFS was not significantly different between tamoxifen and toremifene (91.2 % (standard error of the mean (SE 1.2 % vs 91.2 % (SE 1.1 %, respectively. Similarly, 5-year actuarial OS was not significantly different between tamoxifen and toremifene (92.7 % (SE 1.1 % vs 93.7 % (SE 1.0 %, respectively. Controlling for patient age, tumor size, and tumor grade, a Cox multivariate survival analysis found no difference between patients randomized to toremifene versus tamoxifen in terms of OS (OR 0.951; 95 % confidence interval (CI, 0.623–1.451, p = 0.951 or DFS (OR 1.037; 95 % CI, 0.721–1.491, p = 0.846. Adverse events were similar in the 2 groups.Conclusions. Women treated with adjuvant hormonal therapy enjoyed excellent DFS and OS. No significant differences were found between treatment with either tamoxifen or toremifene. Treatment of HR-positive patients with either tamoxifen or toremifene is appropriate.

  12. 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.

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

    International Nuclear Information System (INIS)

    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

  14. 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 < 0.05) than alum except for BmVAH antigen. In vitro ADCC assay showed that inulin formulation had induced higher cytotoxicity with filarial antigens (as single P < 0.01 and as cocktail P < 0.05, respectively) than alum. The results had confirmed the capability of inulin to deplete the levels of Treg and brought a balance in Th1/Th2 arms against filarial antigens in mice. PMID:25041426

  15. Identification of QS-21 as an Inflammasome-activating Molecular Component of Saponin Adjuvants.

    Science.gov (United States)

    Marty-Roix, Robyn; Vladimer, Gregory I; Pouliot, Kimberly; Weng, Dan; Buglione-Corbett, Rachel; West, Kim; MacMicking, John D; Chee, Jonathan D; Wang, Shixia; Lu, Shan; Lien, Egil

    2016-01-15

    Many immunostimulants act as vaccine adjuvants via activation of the innate immune system, although in many cases it is unclear which specific molecules contribute to the stimulatory activity. QS-21 is a defined, highly purified, and soluble saponin adjuvant currently used in licensed and exploratory vaccines, including vaccines against malaria, cancer, and HIV-1. However, little is known about the mechanisms of cellular activation induced by QS-21. We observed QS-21 to elicit caspase-1-dependent IL-1β and IL-18 release in antigen-presenting cells such as macrophages and dendritic cells when co-stimulated with the TLR4-agonist adjuvant monophosphoryl lipid A. Furthermore, our data suggest that the ASC-NLRP3 inflammasome is responsible for QS-21-induced IL-1β/IL-18 release. At higher concentrations, QS-21 induced macrophage and dendritic cell death in a caspase-1-, ASC-, and NLRP3-independent manner, whereas the presence of cholesterol rescued cell viability. A nanoparticulate adjuvant that contains QS-21 as part of a heterogeneous mixture of saponins also induced IL-1β in an NLRP3-dependent manner. Interestingly, despite the role NLRP3 plays for cellular activation in vitro, NLRP3-deficient mice immunized with HIV-1 gp120 and QS-21 showed significantly higher levels of Th1 and Th2 antigen-specific T cell responses and increased IgG1 and IgG2c compared with wild type controls. Thus, we have identified QS-21 as a nonparticulate single molecular saponin that activates the NLRP3 inflammasome, but this signaling pathway may contribute to decreased antigen-specific responses in vivo. PMID:26555265

  16. Decreased hepatobiliary transport of methotrexate in adjuvant arthritis rats.

    Science.gov (United States)

    Achira, M; Totsuka, R; Fujimura, H; Kume, T

    2002-12-01

    1. We investigated the difference in hepatobiliary transport of methotrexate in normal and adjuvant arthritis (AA) rats and substantiated the expression level of multidrug resistance-associated protein 2 (MRP2) in the liver. 2. Biliary clearance of methotrexate in normal and AA rats was calculated from plasma concentrations and biliary excretion following intravenous infusion and hepatic uptake clearance was estimated from an integration plot using methotrexate concentrations in plasma and liver. 3. Biliary clearance of methotrexate in AA rats was 2.30 +/- 0.23 ml min(-1) kg(-1) (mean SD) and significantly lower than in normal rats (8.42 +/- 0.81 ml min(-1) kg(-1)). The uptake clearance of methotrexate in AA rats was also lower than in normal rats (0.138 versus 0.278 ml min(-1) g liver(-1)). 4. MRP2 in the liver was detected by fluorescein isothiocyanate-labelled antibody and visualized using a confocal laser microscope system. The expression level of MRP2 in AA rats was very low compared with normal rats, indicating a down-regulation in AA rats. 5. In conclusion, biliary clearance of methotrexate was decreased due to the lower activities in both uptake and canalicular secretion, suggesting that several active transporters in the liver, including MRP2, are down-regulated in AA rats. PMID:12593762

  17. 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.

  18. Adjuvant effect of B domain of staphyloccocal protein A displayed on the surface of hepatitis B virus capsid.

    Science.gov (United States)

    Kim, Hyun Jin; Ahn, Keum-Young; Bae, Kyung Dong; Lee, Jiyun; Sim, Sang Jun; Lee, Jeewon

    2016-02-01

    The hepatitis B virus (HBV) capsid-based recombinant particles, which display both major hydrophilic region of HBV surface antigen (HBV-MHR) and B domain of Staphylococcal protein A (SPAB ), were produced using Escherichia coli as expression host. SPAB was used as an adjuvant to elicit the immune response to HBV-MHR, and its adjuvant effect in the immunized mice was estimated with varying the position and amount of SPAB on the HBV capsid particles. Compared to the emulsified aluminum gel (alum gel) that is a currently commercialized vaccine adjuvant, SPAB caused the significantly higher level of anti-HBV immunoglobulin G (IgG) titer and seroconversion rate, and notably SPAB at the most surface-exposed position on the recombinant particle led to the highest immune response. Moreover, SPAB caused much lower ratio of IgG1 to IgG2a compared to alum gel, indicating that helper T-cell 1-mediated immune response (responsible for cytotoxic T-cell stimulation) is relatively more stimulated by SPAB , unlike alum gel that mainly stimulates helper T-cell 2-mediated immune response (responsible for B-cell stimulation). Although HBV-MHR and HBV capsid particle were used as proof-of-concept in this study, SPAB can be used as a highly effective adjuvant with other disease-specific antigens on the surface of other virus-like particles to produce various recombinant vaccines with high potency. PMID:26222886

  19. Molecular cloning, expression and the adjuvant effects of interleukin-8 of channel catfish (Ictalurus Punctatus) against Streptococcus iniae

    Science.gov (United States)

    Wang, Erlong; Wang, Jun; Long, Bo; Wang, Kaiyu; He, Yang; Yang, Qian; Chen, Defang; Geng, Yi; Huang, Xiaoli; Ouyang, Ping; Lai, Weimin

    2016-01-01

    Interleukin-8 (IL-8) as an important cytokine involving in inflammatory and immune response, has been studied as effective adjuvants for vaccines in mammals. However, there are fewer reports about the characterization and adjuvant effects of IL-8 in fish. In this study, cloning and sequence analysis of IL-8 coding region of channel catfish (Ictalurus punctatus) were conducted, mature IL-8(rtIL-8) was expressed and evaluated for its adjuvant effects on the immunoprotection of subunit vaccine encoding α-enolase (rENO) of Streptococcus iniae from several aspects in channel catfish. The results showed co-vaccination of rENO with rtIL-8 enhanced immune responses including humoral and cellular immunity, with higher relative percent survival(RPS,71.4%) compared with the moderate RPS of rENO alone(50%) against S. iniae infection at 4 week post vaccination. While rtIL-8 failed to maintain long-lasting immune protection, only with RPS of 26.67% in rENO + rtIL-8-vaccinated fish compared with that of rENO alone(20%) at 8 week, signifying that IL-8 hold promise for use as potential immunopotentiator in vaccines against bacterial infections in fish, whereas it is insufficient to extend the immunoprotection for long time, and further studies are required to understand the mechanisms of IL-8 used as an adjuvant and seek for more effective way to strengthen the adjuvanticity of IL-8. PMID:27373470

  20. Adjuvant therapy for highly malignant canine mammary tumours: Cox-2 inhibitor versus chemotherapy: a case-control prospective study.

    Science.gov (United States)

    Arenas, C; Peña, L; Granados-Soler, J L; Pérez-Alenza, M D

    2016-07-30

    Cyclooxygenase-2 (Cox-2) enzyme participates in different steps of the carcinogenetic process and in canine mammary tumours (CMTs), a high expression of Cox-2 is associated with malignancy and tumour angiogenesis. The objectives of the study were to evaluate the disease-free survival (DFS) and overall survival (OS) of a Cox-2 inhibitor as adjuvant therapy in dogs with highly malignant (HM)-CMTs and compare it with that of dogs treated with chemotherapy and with control dogs. Twenty-eight dogs were prospectively included. After surgery, dogs were alternatively allocated into two treatment groups (chemotherapy with mitoxantrone n=8; Cox-2 inhibitor, firocoxib n=7). Control group (n=13) included dogs whose owners rejected adjuvant therapy. All dogs were followed up for two years or until death. The DFS was significantly higher in dogs that received adjuvant treatment (mitoxantrone or firocoxib) (P=0.030) than in control dogs. Dogs on firocoxib treatment had significantly higher DFS (P=0.015) and OS (P=0.048) than control dogs. The DFS and OS of dogs on mitoxantrone treatment were not statistically different from controls. In conclusion, this study supports the use of firocoxib for the treatment of HM-CMTs. Further studies are needed to compare the efficacy of chemotherapy drugs versus Cox-2 inhibitors as adjuvant treatment in these cases. PMID:27377395

  1. Molecular cloning, expression and the adjuvant effects of interleukin-8 of channel catfish (Ictalurus Punctatus) against Streptococcus iniae.

    Science.gov (United States)

    Wang, Erlong; Wang, Jun; Long, Bo; Wang, Kaiyu; He, Yang; Yang, Qian; Chen, Defang; Geng, Yi; Huang, Xiaoli; Ouyang, Ping; Lai, Weimin

    2016-01-01

    Interleukin-8 (IL-8) as an important cytokine involving in inflammatory and immune response, has been studied as effective adjuvants for vaccines in mammals. However, there are fewer reports about the characterization and adjuvant effects of IL-8 in fish. In this study, cloning and sequence analysis of IL-8 coding region of channel catfish (Ictalurus punctatus) were conducted, mature IL-8(rtIL-8) was expressed and evaluated for its adjuvant effects on the immunoprotection of subunit vaccine encoding α-enolase (rENO) of Streptococcus iniae from several aspects in channel catfish. The results showed co-vaccination of rENO with rtIL-8 enhanced immune responses including humoral and cellular immunity, with higher relative percent survival(RPS,71.4%) compared with the moderate RPS of rENO alone(50%) against S. iniae infection at 4 week post vaccination. While rtIL-8 failed to maintain long-lasting immune protection, only with RPS of 26.67% in rENO + rtIL-8-vaccinated fish compared with that of rENO alone(20%) at 8 week, signifying that IL-8 hold promise for use as potential immunopotentiator in vaccines against bacterial infections in fish, whereas it is insufficient to extend the immunoprotection for long time, and further studies are required to understand the mechanisms of IL-8 used as an adjuvant and seek for more effective way to strengthen the adjuvanticity of IL-8. PMID:27373470

  2. 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

    International Nuclear Information System (INIS)

    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. 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. The aim of this clinical trial is to evaluate de-escalation of the CapRI-scheme. It

  3. 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

    , based on the Danish Breast Cancer Cooperative Groups database. Inclusion criteria: women treated with chemotherapy as adjuvant treatment for primary breast cancer, age 18-69 years, without recurrence. Results. One thousand two hundred and forty-one patients allocated to CEF in 2005-2006 and 1652.......52, compared to CEF. Patients treated with CE + T had a lower risk of sensory disturbances in the area of surgery compared with CEF, OR 0.75 (95% CI 0.62-0.90), p =¿0.002. More CE + T patients reported peripheral sensory disturbances in the hands, OR 1.56 (95%CI 1.27-1.92), p...

  4. 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

  5. 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)....

  6. 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.

  7. 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.

  8. 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. PMID:24434331

  9. 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.

  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. Who benefits most from adjuvant interferon treatment for melanoma?

    Science.gov (United States)

    Gogas, Helen; Abali, Huseyin; Ascierto, Paolo A; Demidov, Lev; Pehamberger, Hubert; Robert, Caroline; Schachter, Jacob; Eggermont, Alexander M M; Hauschild, Axel; Espinosa, Enrique

    2015-01-01

    Metastatic melanoma has a poor prognosis; the median survival for patients with stage IV melanoma ranges from 8 to 18 months after diagnosis. Interferon-α provides significant improvement in disease-free survival at the cost of poor tolerability. Identifying patients who benefit the most may improve the cost:benefit ratio. In addition, no data exist for the role of adjuvant therapy in noncutaneous melanoma. Molecular profiles may help to identify patients who benefit the most from adjuvant interferon therapy. In this review, the American Joint Commission on Cancer 2009 staging criteria and emerging biomarker data to guide adjuvant treatment decisions will be discussed. Several criteria to guide selection of patients are discussed in detail. These include Breslow thickness, number of positive lymph nodes, whether or not the primary lesion has ulcerated, immunologic markers, and cytokine profiles. Substantial progress has been made in deciding which patients benefit from interferon-α adjuvant therapy. Interferon-α is the only agent currently approved for the adjuvant treatment of this deadly disease, despite its side effect profile. More effective drugs with better tolerability are needed. PMID:24176884

  12. 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.

  13. Comparison between ultrasonography and [18F]FDG PET for pathological response of breast cancer to neo-adjuvant chemotherapy

    International Nuclear Information System (INIS)

    To compare between ultrasonography (US) and the predictive value of [18F]fluorodeoxyglucose positron emission tomography (FDG PET) for the pathological response of breast cancer after completion of neo-adjuvant chemotherapy. Twenty eight patients with newly diagnosed, locally advanced breast cancer were evaluated with US and PET before and after neo-adjuvant chemotherapy. Chemotherapy response with US was classified by UICC. Reduction rate of pSUV with PET was measured for residual disease assessment. Pathological responses were classified into three groups: pathological non-response (pNR), pathological partial response (pPR), and pathological complete response (pCR). PET correctly predicted pathologic responses in 22 of 28 patients (78.6%); US correctly predicted in 21 of 28 patients (75%). Significant differences between chemotherapy responses of US and residual tumor assessments of PET to neo-adjuvant chemotherapy were not observed (>0.05). Two patients with pPR who were predicted with US to have complete response were classified as partial response in PET. Also, a patient with pNR was predicted with US to have partial response in US, but partial response in PET. In this study, differences between US and PET were not statistically significant. But PET provides additional information that cannot be assessed in US for the pathological response of breast cancer after completion of neo-adjuvant chemotherapy

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy

    Science.gov (United States)

    Petryk, Alicia Ailie

    Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

  20. 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.

  1. Development of CpG ODN Based Vaccine Adjuvant Formulations.

    Science.gov (United States)

    Gursel, Mayda; Gursel, Ihsan

    2016-01-01

    Development of effective vaccine mediated immune responses relies on the use of vaccine adjuvants capable of enhancing and directing the adaptive immune response to the antigen. When used as vaccine adjuvants, type I interferon inducing agents can elicit potent effector/memory T cell responses and humoral immunity. Distinct sequences of single stranded synthetic oligodeoxynucleotides containing unmethylated cytosine-phosphate-guanine oligodeoxynucleotide motifs (CpG ODN) can generate type I interferon production via a TLR9-MyD88-IRF7-mediated signaling pathway. Here, we describe two different methods of preparing CpG ODN-based vaccine adjuvant formulations that can induce a robust IFNα response from human peripheral blood mononuclear cells. PMID:27076306

  2. Old and new adjuvants for hepatitis B vaccines.

    Science.gov (United States)

    Leroux-Roels, Geert

    2015-02-01

    The safety and immunogenicity profiles of currently available recombinant hepatitis B vaccines are excellent. However, it remains a real challenge to induce protective immunity in the target groups that respond poorly or not at all to conventional vaccines. Ideally, a hepatitis B vaccine can be developed that conveys lifelong protection against infection rapidly after the injection of a single dose. Although this goal is far from being reached, important improvements have been made. Novel vaccine adjuvants have been developed that enhance the immunogenicity of recombinant hepatitis B vaccines while maintaining a good safety profile. The different adjuvants and adjuvant systems that are discussed herein have all been thoroughly evaluated in clinical trials and some have reached or are close to reach the market. PMID:25523196

  3. Elucidating the mechanisms of protein antigen adsorption to the CAF/NAF liposomal vaccine adjuvant systems

    DEFF Research Database (Denmark)

    Hamborg, Mette; Rose, Fabrice; Jorgensen, Lene;

    2014-01-01

    The reverse vaccinology approach has recently resulted in the identification of promising protein antigens, which in combination with appropriate adjuvants can stimulate customized, protective immune responses. Although antigen adsorption to adjuvants influences vaccine efficacy and safety, little...

  4. 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.

  5. Concurrent chemoradiotherapy in adjuvant treatment of breast cancer

    International Nuclear Information System (INIS)

    The optimal sequencing of chemotherapy and radiotherapy after breast surgery was largely studied but remains controversial. Concurrent chemo-radiotherapy is a valuable method for adjuvant treatment of breast cancer which is under ongoing research program in our hospital. We are evaluating the feasibility of the concomitant use of chemotherapy retrospectively. Two hundred forty four women having breast cancer were investigated in a retrospective study. All patients were either treated by radical surgery or breast conservative surgery. The study compares two adjuvant treatments associating concomitant chemotherapy and radiotherapy. In the first group (group A) the patients were treated by chemotherapy and radiotherapy in concomitant way using anthracycline (n = 110). In the second group (group B) the patients were treated by chemotherapy and radiotherapy in concomitant way using CMF treatment (n = 134). Chemotherapy was administered in six cycles, one each 3 weeks. Radiotherapy delivered a radiation dose of 50 Gy on the whole breast (or on the external wall) and/or on the lymphatic region. The Kaplan-Meier method was used to estimate the rates of disease free survival, loco-regional recurrence-free survival and overall survival. The Pearson Khi2 test was used to analyse the homogeneity between the two groups. The log-rank test was used to evaluate the differences between the two groups A and B. After 76.4 months median follow-up (65.3 months mean follow up), only one patient relapsed to loco-regional breast cancer when the treatment was based on anthracycline. However, 8 patients relapsed to loco-regional breast cancer when the treatment was based on CMF. In the anthracycline group, the disease free survival after 5 years, was 80.4% compared to 76.4% in the CMF group (Log-rank test: p = 0.136). The overall survival after 5 years was 82.5% and 81.1% in the anthracycline and CMF groups respectively (Log-rank test: p = 0.428). The loco-regional free survival at 5 years

  6. TLR9 adjuvants enhance immunogenicity and protective efficacy of the SE36/AHG malaria vaccine in nonhuman primate models.

    Science.gov (United States)

    Tougan, Takahiro; Aoshi, Taiki; Coban, Cevayir; Katakai, Yuko; Kai, Chieko; Yasutomi, Yasuhiro; Ishii, Ken J; Horii, Toshihiro

    2013-02-01

    The SE36 antigen, derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Ongoing clinical trials suggest the efficacy of the SE36 vaccine could be increased by the incorporation of more effective adjuvants into the vaccine formulation. In this study, we assessed the safety, immunogenicity and protective efficacy of SE36/AHG formulated with TLR9 ligand adjuvants K3 CpG oligodeoxyribonucleotides (CpG ODNs) (K3 ODN), D3 ODN or synthetic hemozoin, in two non-human primate models. SE36/AHG with or without each adjuvant was administrated to cynomolgus monkeys. A combination of TLR9 ligand adjuvant with SE36/AHG induced higher humoral and cellular immune response compared with SE36/AHG alone. Administration of a crude extract of P. falciparum parasite resulted in the induction of more SE36-specific IgG antibodies in monkeys vaccinated with a combination of SE36/AHG and adjuvant, as opposed to vaccination with SE36/AHG alone. The most effective TLR9 ligand, K3 ODN, was chosen for further vaccine trials in squirrel monkeys, in combination with SE36/AHG. All monkeys immunized with the combined SE36/AHG and K3 ODN formulation effectively suppressed parasitemia and symptoms of malaria following challenge infections. Furthermore, no serious adverse events were observed. Our results show that the novel vaccine formulation of K3 ODN with SE36/AHG demonstrates safety, potent immunogenicity and efficacy in nonhuman primates, and this vaccine formulation may form the basis of a more effective malaria vaccine. PMID:23291928

  7. Outcomes of Adjuvant Chemoradiation After Pancreaticoduodenectomy With Mesenterico-Portal Vein Resection for Adenocarcinoma of the Pancreas

    International Nuclear Information System (INIS)

    Purpose: Surgery followed by chemotherapy and radiation (CRT) offers patients with pancreatic adenocarcinoma a chance for extended survival. In some patients, however, resection is difficult because of vascular involvement by the carcinoma, necessitating resection and grafting of the mesenterico-portal vessels. The purpose of this study was to compare outcomes between pancreaticoduodenectomy (PD) with and without mesenterico-portal vein resection (VR) in patients receiving adjuvant CRT for pancreatic adenocarcinoma. Methods and Materials: Between 1993 and 2005, 160 patients underwent PD with 5-FU-based adjuvant CRT followed by maintenance chemotherapy at the Johns Hopkins Hospital; 20 (12.5%) of the 160 underwent VR. Clinical outcomes, including median survival, overall survival, and complication rates were assessed for both groups. Results: Patients who underwent VR had significantly longer operative times (p = 0.009), greater intraoperative blood loss (p = 0.01), and longer postoperative lengths of stay (p = 0.03). However, postoperative morbidity, median survival, and overall survival rates were similar between the two groups. Most patients (70%) from both groups were able to complete CRT, and a subgroup analysis demonstrated no appreciable differences in terms of complications. None of the VR patients who received adjuvant CRT developed veno-occlusive disease or graft failure/leakage. Conclusion: In a cohort of patients treated with adjuvant 5-FU-based CRT at the Johns Hopkins Hospital, having a VR at the time of PD resulted in similar complication rates and survival. These data support the feasibility and safety of adjuvant CRT in patients undergoing VR at the time of PD.

  8. Adjuvant effect of docetaxel on the immune responses to influenza A H1N1 vaccine in mice

    Directory of Open Access Journals (Sweden)

    Chen Jian

    2012-07-01

    Full Text Available Abstract Background Vaccination remains one of the most effective approaches to prevent the spread of infectious diseases. Immune responses to vaccination can be enhanced by inclusion of adjuvant in a vaccine. Paclitaxel extracted from the bark of the Pacific yew tree Taxus brevifola was previously demonstrated to have adjuvant property. Compared to paclitaxel, docetaxel is another member of taxane family, and is more soluble in water and easier to manipulate in medication. To investigate the adjuvant effect of this compound, we measured the immune responses induced by co-administration of a split inactivated influenza H1N1 vaccine antigen with docetaxel. Results When co-administered with docetaxel, lower dose antigen (equivalent to 10 ng HA induced similar levels of IgG and IgG isotypes as well as HI titers to those induced by higher dose antigen (equivalent to 100 ng HA. Docetaxel promoted splenocyte responses to H1N1 antigen, ConA and LPS, mRNA expressions of cytokines (IFN-gamma, IL-12, IL-4 and IL-10 and T-bet/GATA-3 by splenocytes. The enhanced immunity was associated with up-expressed microRNAs (miR-155, miR-150 and miR-146a in docetaxel-stimulated RAW264.7 cells. Docetaxel promoted similar IgE level to but alum promoted significantly higher IgE level than the control. Conclusion Docetaxel has adjuvant effect on the influenza H1N1 vaccine by up-regulation of Th1/Th2 immune responses. Considering its unique vaccine adjuvant property as well as the safe record as an anti-neoplastic agent clinically used in humans during a long period, docetaxel should be further studied for its use in influenza vaccine production.

  9. 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.

  10. 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.

  11. 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.

  12. 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

    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...

  13. Topical CpG Oligodeoxynucleotide Adjuvant Enhances the Adaptive Immune Response against Influenza A Infections.

    Science.gov (United States)

    Cheng, Wing Ki; Plumb, Adam William; Lai, Jacqueline Cheuk-Yan; Abraham, Ninan; Dutz, Jan Peter

    2016-01-01

    Current influenza vaccines generate humoral immunity, targeting highly variable epitopes and thus fail to achieve long-term protection. T cells recognize and respond to several highly conserved epitopes across influenza serotypes. A strategy of raising strong cytotoxic T cell memory responses to epitopes conserved across serotypes would provide cross serotype protection, eliminating the need for annual vaccination. We explored the adjuvant potential of epicutaneous (ec) and subcutaneous (sc) delivery of CpG oligodeoxynucleotide in conjunction with sc protein immunization to improve protection against influenza A virus (IAV) infections using a mouse model. We found enhanced long-term protection with epicutaneous CpG ODN (ecCpG) compared to subcutaneous CpG ODN (scCpG) as demonstrated by reduced viral titers in the lungs. This correlated with increased antigen-specific CD8 T cells in the airways and the lungs. The memory T cell response after immunization with ecCpG adjuvant was comparable to memory response by priming with IAV infection in the lungs. In addition, ecCpG was more efficient than scCpG in inducing the generation of IFN-γ producing CD4 T cells. The adjuvant effect of ecCpG was accompanied with its ability to modulate tissue-homing molecules on T cells that may direct them to the site of infection. Together, this work provides evidence for using ecCpG to induce strong antibody and memory T cell responses to confer protection against IAV infection. PMID:27524984

  14. 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.

  15. Management of patients with T4 cutaneous T-cell lymphoma(CTCL) with total skin electron beam therapy(TSEBT) and adjuvant extracorporeal photochemotherapy(ECP)

    International Nuclear Information System (INIS)

    Purpose/Objective: No randomized data are available regarding the use of ECP in CTCL, and its usage as an adjuvant to TSEBT has not been studied extensively. We report the clinical results for patients with T4 CTCL who received TSEBT and adjuvant ECP with respect to overall survival(OS), disease free survival(DFS), and toxicity with comparison to historical controls. Materials and Methods: Between 1974 and 1994, a total of 47 patients with T4 CTCL were treated with TSEBT. All patients were staged as T4 based on the presence of erythroderma. Of the 47 patients in the cohort, 42 were evaluable, 12 received adjuvant ECP, 7 received systemic chemotherapy, 2 received PUVA, and 21 were not treated adjuvantly. TSEBT was offered via 6MeV linac, total 36Gy, 1Gy daily, 6 fields, with boosts to the perineum(20Gy), soles(20Gy), and scalp (6Gy), over 9 weeks. ECP was offered monthly on 2 consecutive days with the use of oral psoralen, pheresis of leukocytes and reinfusion, for 6 months. Overall survival, DFS, response to TSEBT, and toxicity were evaluated for all patients, and subgroups were compared based on adjuvant modality. Median age was 64 years (29-82), 14 patients were female, and the median follow-up was 11 months(2-100). Results: Response to TSEBT was complete(CR) in (23(42))(55%) of patients. The median OS for the entire cohort was 37 months, with a median DFS of only 2.2 months. When patients were evaluated by subgroup based on adjuvant therapy, the median OS for those not receiving adjuvant treatment was 29 months, not reached at 42 months for TSEBT+ECP, and 65 months for TSEBT+Chemo (p>0.05). DFS by adjuvant group was 0, 6, and 3 months for no adjuvant, TSEBT+ECP, and TSEBT+Chemo respectively. When stratified by response to TSEBT prior to adjuvant therapy, the CR rates were: 55% (11 patients) for the TSEBT alone group, 71% (5 patients) TSEBT+Chemo, and 25% (3 patients) for TSEBT+ECP. Differences in OS and DFS for patients after CR to TSEBT by adjuvant group were

  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. 胰腺癌:辅助治疗%Pancreatic cancer-Adjuvant therapy

    Institute of Scientific and Technical Information of China (English)

    Asma Sultana; John Neoptolemos; Paula Ghaneh

    2007-01-01

    Pancreatic cancer ranks tenth in terms of newly diagnosed cases, but just 10%-15% of these patients can undergo resection. Survival after curative surgery is dismal, as recurrences occur either locally or in the liver. Adjuvant treatment with either chemotherapy or chemoradiation (with or without maintenance chemotherapy) has been employed, to improve the poor prognosis. Justification for the use of chemoradiation, with follow on chemotherapy, is based on the results of an underpowered 1987 GITSG study, which closed prematurely and compared intervention to observation. There has been no survival advantage demonstrated in the one randomized controlled trial that examined chemoradiation compared to chemotherapy. There is a clear cut survival advantage however with chemotherapy compared to observation, based on the results from two large randomized controlled trials, and supported by an individual patient data meta-analysis. The standard of care for adjuvant therapy based on level Ⅰ evidence (from the ESPAC-1 trial) is post operative chemotherapy using 5-Fluorouracil with folinic acid providing a best estimate of 29% five years survival.

  18. Influence of Adjuvant Therapy in Cancer Survivors on Endothelial Function and Skeletal Muscle Deoxygenation.

    Science.gov (United States)

    Ederer, Austin K; Didier, Kaylin D; Reiter, Landon K; Brown, Michael; Hardy, Rachel; Caldwell, Jacob; Black, Christopher D; Larson, Rebecca D; Ade, Carl J

    2016-01-01

    The cardiotoxic effects of adjuvant cancer treatments (i.e., chemotherapy and radiation treatment) have been well documented, but the effects on peripheral cardiovascular function are still unclear. We hypothesized that cancer survivors i) would have decreased resting endothelial function; and ii) altered muscle deoxygenation response during moderate intensity cycling exercise compared to cancer-free controls. A total of 8 cancer survivors (~70 months post-treatment) and 9 healthy controls completed a brachial artery FMD test, an index of endothelial-dependent dilation, followed by an incremental exercise test up to the ventilatory threshold (VT) on a cycle ergometer during which pulmonary V̇O2 and changes in near-infrared spectroscopy (NIRS)-derived microvascular tissue oxygenation (TOI), total hemoglobin concentration ([Hb]total), and muscle deoxygenation ([HHb] ≈ fractional O2 extraction) were measured. There were no significant differences in age, height, weight, and resting blood pressure between cancer survivors and control participants. Brachial artery FMD was similar between groups (P = 0.98). During exercise at the VT, TOI was similar between groups, but [Hb]total and [HHb] were significantly decreased in cancer survivors compared to controls (P cancer survivors compared to controls (P = 0.02 and P = 0.03 respectively). In cancer survivors, a decreased skeletal muscle microvascular function was observed during moderate intensity cycling exercise. These data suggest that adjuvant cancer therapies have an effect on the integrated relationship between O2 extraction, V̇O2 and O2 delivery during exercise.

  19. Taxanes in adjuvant and neoadjuvant therapy for breast cancer

    OpenAIRE

    S. V. Limareva

    2010-01-01

    Taxanes (paclitaxel and docetaxel) are currently considered to be basic cytostatics in the treatment of all breast cancer (BC) stages. The results of conducted and ongoing clinical trials suggest that incorporation of taxanes into adjuvant and neoadjuvant chemotherapy regimens enhances the efficiency of treatment for operable BC and show it necessary to apply an individual approach depending on prognostic and predictive factors.

  20. Organic weed control with vinegar: Application volumes and adjuvants

    Science.gov (United States)

    Preliminary results have indicated that vinegar has potential as an organic herbicide, but further research is needed to increase our understanding of the relationship between acetic acid concentrations, application volumes, adjuvants, weed species, and weed maturity on effectiveness of vinegar to c...

  1. 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

  2. Controversies in the Adjuvant Treatment of Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Muhammad Wasif Saif

    2007-09-01

    Full Text Available There is no universally accepted standard approach to treat patients with pancreatic cancer in the adjuvant setting. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary depending on which side of the Atlantic you are on: chemo-radiotherapy followed by chemotherapy is considered the optimal therapy in North America (GITSG, RTOG while chemotherapy alone is the current standard in Europe (ESPAC-1, CONKO. Whether gemcitabine is superior to 5-FU remains to be learnt from the ESPAC-3 study currently on-going in Europe. A number of important questions have yet to be fully addressed: • What is the absolute value of radiotherapy in this setting? • How should radiotherapy be delivered, if at all? • What should be the time to deliver of either or both therapeutic modalities in the adjuvant setting? • Are there any patients who can benefit from the combined modality? • What is the most appropriate chemotherapeutic agent(s to administer in the adjuvant setting? • Is there any role of integrating the novel/targeted agents, albeit the negative studies in the metastatic setting? • What are the new developments (such as vaccines, pancreas cancer stem cells, etc. in this area? The author summarizes the evolution of adjuvant therapy for resected pancreatic cancer and highlights the controversies that originate from several studies, each fraught with its own limitations.

  3. Oily adjuvants and autoimmunity: now time for reconsideration?

    Science.gov (United States)

    Whitehouse, M

    2012-02-01

    Immunologists have relied heavily on oil-based adjuvants to generate antibodies or induce auto-allergic responses in experimental animals. These are rarely used today for human vaccination because of their persistent irritancies and propensity to cause ulcers at sites of injection. However oily materials with adjuvant properties abound in our modern environment, both personal and extraneous. Their inadvertent impact as cryptotoxins may contribute to the rising incidence of auto-allergic diseases in recent times. Experimentally, the potential adjuvanticity of various oils, fats and other lipids can be evaluated by their ability (or otherwise) to induce auto-allergic disease(s) in rats and mice with, or even without, the addition of a mycobacterial immunostimulant. Genetic factors have been recognized that determine an animal's susceptibility or resistance to these oil-induced immunopathies. So it may be profitable to further characterize these factors, first in animals and then perhaps in human populations, to help find ways to enhance natural resistance to those adjuvant-active oils that may be widely distributed in the personal environment, notably mineral oil(s). (The six tables in this article summarize some relevant facts and a few conjectures.) A caveat: This review is restricted to the adjuvant properties of some oils in the personal environment. It does not cover the mechanisms of adjuvanticity.

  4. Postoperative adjuvant chemotherapy in rectal cancer operated for cure

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

  5. Tailorable Trimethyl chitosans as adjuvant for intranasal immunization

    NARCIS (Netherlands)

    Verheul, R.J.

    2010-01-01

    Tailorable Trimethyl Chitosans as Adjuvant for Intranasal Immunization Active vaccination has proven to be the most (cost) effective tool in the fight against infectious diseases. Nowadays, most vaccines are administered via parenteral injection. However, the risk of contaminated needles and need fo

  6. Maternal allergen immunisation to prevent sensitisation in offspring: Th2-polarising adjuvants are more efficient than a Th1-polarising adjuvant in mice

    Directory of Open Access Journals (Sweden)

    Melkild Ingrid

    2010-03-01

    Full Text Available Abstract Background Allergy has been an increasing problem in several parts of the world. Prenatal exposure to allergen and microbial components may affect the development of allergies in childhood, as indicated by epidemiological and experimental studies. We investigated the capacity for allergic sensitisation in offspring after induction of a Th1- or a Th2-polarised immune response to the same allergen in mothers during pregnancy. Results During pregnancy, mice were immunised with ovalbumin (OVA given with either one of the Th2-adjuvants pertussis toxin (PT or Al(OH3 (aluminium hydroxide, or with the Th1 adjuvant CpG. Offspring were immunised with OVA in Al(OH3 as young adults. Serum and supernatants from ex vivo stimulated or non-stimulated spleen cells from mothers and offspring were analysed for OVA-specific antibodies and cytokines, respectively. Mothers immunised with OVA together with either Al(OH3 or PT had increased levels of OVA-specific IgE and IgG1 compared to naive mothers, whereas mothers immunised with OVA together with CpG had increased levels of OVA-specific IgG2a compared to naive mothers. In general the highest levels of IL-5, IL-10, and IFNγ were observed in spleen cells from mothers immunised with PT and OVA. Upon immunisation, offspring from mothers immunised with OVA and either PT or Al(OH3 showed reduced levels of OVA-specific IgE and IgG1 and increased levels of OVA-specific IgG2a antibodies compared to offspring from naive mothers. Maternal immunisation with CpG and OVA did not affect antibody responses in offspring. Conclusion Allergic sensitisation in the offspring was affected by the type of adjuvant used for immunisation of the mothers with the same allergen. Th2 polarisation of the immune response in the mothers was found to give reduced IgE levels upon sensitisation of the offspring, whereas no reduction was achieved with Th1 polarisation in the mothers.

  7. 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.

  8. 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. PMID:25156127

  9. 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. PMID:27236001

  10. 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. PMID:27032516

  11. 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.

  12. 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.

  13. Adjuvant Therapy with High-Dose Medroxyprogesterone Acetate for Operable Breast Cancer.

    Science.gov (United States)

    Koyama

    1999-04-25

    BACKGROUND: Medroxyprogesterone acetate (MPA) produces a comparable or higherresponse rate in metastatic breast cancer compared with tamoxifen which is alsocommonly used for adjuvant endocrine therapy. Several studies in the West have indicated the efficacy of MPA when used as an adjuvant to surgery in certain subsets of patients. The present study was undertaken as a multicenter open study in Japan to investigate the safety and efficacy of MPA in adjuvant endocrine therapy. Method and Patients: A combination of 800 mg/day MPA and a fluorouracil compound for 6 months was given postoperatively to 119 patients with stage II or IIIabreast cancer in 32 participating hospitals between June 1987 and June 1989. RESULTS: Among the 119 patients, 59 patients (49.6%) experienced some kind ofadverse reaction. The major adverse reaction was abnormal menstruation, seen in 13 (25.0%) of the 52 premenopausal patients. Vaginal bleeding was a major adverse reaction in the 67 postmenopausal patients (8/67 or 11.9%). An increase in body weight and moon face were observed in 23 (19.3%) and 9 (7.6%) of the 119 patients, respectively. Administration of drugs was discontinued because of adversereaction in 17 patients (14.3%), and dose reduction or temporary suspension wasnecessary in 7 patients (5.9%). Increase in body weight was the main reason fordiscontinuation of the treatment. No severe adverse reactions were observed. After a median follow-up of 74.5 months (range, 2.2-90.0 months), 84 of the 119 patients are alive with no evidence of disease. The 3-year and 5-year disease-freesurvival rates were 88.2% and 82.6% in stage II patients, and 64.7% and 52.9% in stage IIIa patients, respectively. The 3-year and 5-year disease-free survivalrates according to age were 87.8% and 79.3% in patients aged 50 years or more, and 78.6% and 71.4% in patients aged under 50 years. CONCLUSION: These results show that 800 mg/day MPA plus a fluorouracil compound can be administered with acceptable

  14. Scrotal Irradiation in Primary Testicular Lymphoma : Review of the Literature and In Silico Planning Comparative Study

    NARCIS (Netherlands)

    Brouwer, Charlotte L.; Wiesendanger, Esther M.; van der Hulst, Peter C.; van Imhoff, Gustaaf W.; Langendijk, Johannes A.; Beijert, Max

    2013-01-01

    We examined adjuvant irradiation of the scrotum in primary testicular lymphoma (PTL) by means of a literature review in MEDLINE, a telephone survey among Dutch institutes, and an in silico planning comparative study on scrotal irradiation in PTL. We did not find any uniform adjuvant irradiation tech

  15. Assembly and Immunological Processing of Polyelectrolyte Multilayers Composed of Antigens and Adjuvants

    Science.gov (United States)

    2016-01-01

    While biomaterials provide a platform to control the delivery of vaccines, the recently discovered intrinsic inflammatory characteristics of many polymeric carriers can also complicate rational design because the carrier itself can alter the response to other vaccine components. To address this challenge, we recently developed immune-polyelectrolyte multilayer (iPEMs) capsules electrostatically assembled entirely from peptide antigen and molecular adjuvants. Here, we use iPEMs built from SIINFEKL model antigen and polyIC, a stimulatory toll-like receptor agonist, to investigate the impact of pH on iPEM assembly, the processing and interactions of each iPEM component with primary immune cells, and the role of these interactions during antigen-specific T cell responses in coculture and mice. We discovered that iPEM assembly is pH dependent with respect to both the antigen and adjuvant component. Controlling the pH also allows tuning of the relative loading of SIINFEKL and polyIC in iPEM capsules. During in vitro studies with primary dendritic cells (DCs), iPEM capsules ensure that greater than 95% of cells containing at least one signal (i.e., antigen, adjuvant) also contained the other signal. This codelivery leads to DC maturation and SIINFEKL presentation via the MHC-I antigen presentation pathway, resulting in antigen-specific T cell proliferation and pro-inflammatory cytokine secretion. In mice, iPEM capsules potently expand antigen-specific T cells compared with equivalent admixed formulations. Of note, these enhancements become more pronounced with successive booster injections, suggesting that iPEMs functionally improve memory recall response. Together our results reveal some of the features that can be tuned to modulate the properties of iPEM capsules, and how these modular vaccine structures can be used to enhance interactions with immune cells in vitro and in mice. PMID:27380137

  16. Adjuvant radiotherapy and concomitant 5-fluorouracil by protracted venous infusion for resected pancreatic cancer

    International Nuclear Information System (INIS)

    Purpose: To assess the toxicity and clinical benefit from adjuvant chemoradiotherapy consisting of protracted venous infusion 5-fluorouracil (5-FU) and concomitant radiotherapy in patients with resected pancreatic cancer. Methods and Materials: Between 1994 and 1999, 52 patients who underwent pancreaticoduodenectomy received adjuvant chemoradiotherapy. The tumor bed and regional nodes received a dose of 45 Gy in fractions of 1.8 Gy followed by boost to the tumor bed if the surgical margins were involved (total dose, 54 Gy). The patients also received concomitant 5-FU by protracted venous infusion (200-250 mg/m2/day, 7 days/week) during the entire radiotherapy course. Results: Fifty-two patients (30 men, 22 women) were enrolled and treated on this protocol. The median age was 63 years (range, 38-78 years), and the median Karnofsky Performance Status was 80 (range, 70-100). Thirty-five percent had involved surgical margins and 59% had involved lymph nodes. All patients completed therapy, and there were no Grade IV/V toxicities observed. With median follow-up of 24 months (range, 3-52 months) for surviving patients, the median survival is 32 months, and 2-year and 3-year survivals are 62%, and 39%, respectively. Conclusion: Radiotherapy with concomitant 5-FU by protracted venous infusion as adjuvant treatment for resected pancreatic cancer is well tolerated. This approach allows for greater dose intensity with reduced toxicity. The median survival of this cohort of patients compares favorably with our earlier experience and other published series.

  17. 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

  18. 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.

  19. Cognitive function in postmenopausal women receiving adjuvant letrozole or tamoxifen for breast cancer in the BIG 1-98 randomized trial

    OpenAIRE

    Phillips, Kelly Anne; Ribi, Karin; Sun, Zhuoxin; Stephens, Alisa; Thompson, Alastair; Harvey, Vernon; Thürlimann, Beat; Cardoso, Fatima; Pagani, Olivia; Coates, Alan S.; Goldhirsch, Aron; Price, Karen N.; Gelber, Richard D; Bernhard, Jürg

    2010-01-01

    Cognitive function in postmenopausal women receiving letrozole or tamoxifen as adjuvant endocrine treatment was compared during the fifth year of treatment in a substudy of the BIG 1-98 trial. In BIG 1-98 patients were randomized to receive adjuvant A) 5-years tamoxifen, B) 5-years letrozole, C) 2-years tamoxifen followed by 3-years letrozole, or D) 2-years letrozole followed by 3-years tamoxifen. The primary comparison was the difference in composite score for patients taking letrozole (B+C;...

  20. Comparative study between eszopiclone and clonazepam in adjuvant treatment of sleep disorders of schizophrenia%右佐匹克隆与氯硝西泮辅助治疗精神分裂症睡眠障碍对照研究

    Institute of Scientific and Technical Information of China (English)

    王刚平; 颉瑞; 裴根祥; 杜鹤宇; 李宏

    2011-01-01

    目的 探讨右佐匹克隆辅助治疗精神分裂症睡眠障碍的疗效及安全性.方法 91例伴睡眠障碍的精神分裂症患者(均统一服用阿立哌唑10~20 mg·d-1)随机分成2组,分别口服右佐匹克隆3~6 mg·d-1(n=45)或氯硝西泮2~4 mg·d-1(n=46),采用匹兹堡睡眠质量指数(PSQI)、阳性和阴性症状量表(PANSS)、副反应量表(TESS)评定疗效和安全性;观察3 wk.结果 2组各完成43例.治疗3 wk后,2组睡眠时间均显著延长,PSQI评分和PANSS评分显著下降(均P<0.01),2组间疗效无显著差异(P>0.05);右佐匹克隆组日间功能障碍的改善显著优于氯硝西泮组[(1.2±0.9)分vs.(1.6±0.7)分,P<0.05];2组TESS评分无显著差异(P>0.05),右佐匹克隆组嗜睡、头昏的发生率显著少于氯硝西泮组(P<0.05).结论 右佐匹克隆辅助治疗精神分裂症睡眠障碍疗效显著,安全性优于氯硝西泮.%AIM To detect the clinical efficacy and safety of eszopiclone in the adjuvant treatment of sleep disorders of schizophrenia.METHODS Ninety-one schizophrenic patients with sleep disorders who received aripiprazole 10 - 20 mg·d-1 were divided into two groups, 45 for eszopiclone (3 - 6 mg·d-1) group and 46 for clonazepam (2 - 4 mg·d-1) group.PSQI、 PANSS and TESS were used to evaluate the efficacy and safety of the 3-week treatment.RESULTS The two groups completed 43 patients for each.By the end of the treatment, the sleep duration increased and the PSQI scores and PANSS scores of the two groups decreased significantly (all P < 0.01 ), and there was no significant difference in the overall efficacy between the two groups (P > 0.05).But the ezopiclone group had better effect on treating daytime dysfunction than the clonazepam group [( 1.2± 0.9) vs.( 1.6 ± 0.7), P < 0.05].There was no significant difference in the TESS scores between the two groups (P > 0.05) , but the incidence rates of somnolence and dizziness in the eszopiclone group were lower than

  1. Preliminary evaluation of a recombinant Rift Valley fever virus nucleocapsid protein as an immunogen in combination with different adjuvants in mice and sheep

    International Nuclear Information System (INIS)

    The nucleocapsid protein (NP) of Rift Valley fever virus (RVFV) is the most abundantly expressed and immunogenic viral component and therefore it is an obvious choice for development of immunoassays for rapid and accurate detection of specific antigen and antibody in RVF infected individuals. The role of the anti-NP host immune responses in protection against infection with RVFV has not been elucidated. Mice and sheep were immunized with recombinant RVFV NP combined with four adjuvants (ISA50, Alhydrogel, TiterMax Gold or SaponinQ) and respectively boosted with recNP/adjuvant. All vaccinated mice groups generated strong Th-2 mediated IgG1 responses, whereas recNP/SaponinQ vaccinated mice generated a much stronger Th-1 mediated IgG2A response than other antigen/adjuvant combinations. Among the placebo control groups, 96% of the mice showed severe clinical signs or died between day 2 and 6 after challenge whereas vaccinated animals showed 40 to 100% protection against sickness or death depending on the adjuvant used. Anti-NP humoral immunity did not prevent viral replication as demonstrated by RVFV recovery from various tissues of clinically normal mice but viral loads were lower compared to non-vaccinated groups. The recNP was highly immunogenic in sheep. Its administration with adjuvants resulted in increased but varying kinetics of humoral immune response which after challenge with wild type virus was lower in vaccinated than in control sheep. The level of viremia post-infection varied between vaccinated sheep but was significantly lower compared to control groups. Anti-NP antibodies did not neutralize RVFV in vitro. The type of adjuvant used with recNP appears to play an important role in protection against clinical disease implicating that cellular immune responses are responsible in protection and/or controlling infection with RVFV in a host

  2. 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

  3. 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

  4. Comparison of CTL reactivity in the spleen and draining lymph nodes after immunization with peptides pulsed on dendritic cells or mixed with Freund's incomplete adjuvant

    DEFF Research Database (Denmark)

    Wang, Ming-Jun; Nissen, Mogens Holst; Buus, Søren;

    2003-01-01

    OBJECTIVE: To compare CTL reactivity in the spleen and the draining lymph nodes (LN) from C57BL/6 mice after immunization with self and non-self peptides pulsed on autologous dendritic cells (DC) or mixed with Freund's incomplete adjuvant (FIA). METHODS: Peptides showing high to low binding...

  5. 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 immun...

  6. 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 (Pbone volume and BMD at the end of 3 month study endpoint was seen in animals dosed with 20 IU/kg of calcitonin compounds. Similarly, in case of adjuvant-induced arthritis rats, there was a significant increase (Pbone volume and BMD in calcitonin-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.

  7. 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

  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. 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.

  10. 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.

  11. 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.

  12. CpG DNA as a vaccine adjuvant.

    Science.gov (United States)

    Bode, Christian; Zhao, Gan; Steinhagen, Folkert; Kinjo, Takeshi; Klinman, Dennis M

    2011-04-01

    Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs trigger cells that express Toll-like receptor 9 (including human plasmacytoid dendritic cells and B cells) to mount an innate immune response characterized by the production of Th1 and proinflammatory cytokines. When used as vaccine adjuvants, CpG ODNs improve the function of professional antigen-presenting cells and boost the generation of humoral and cellular vaccine-specific immune responses. These effects are optimized by maintaining ODNs and vaccine in close proximity. The adjuvant properties of CpG ODNs are observed when administered either systemically or mucosally, and persist in immunocompromised hosts. Preclinical studies indicate that CpG ODNs improve the activity of vaccines targeting infectious diseases and cancer. Clinical trials demonstrate that CpG ODNs have a good safety profile and increase the immunogenicity of coadministered vaccines. PMID:21506647

  13. 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.

  14. CpG DNA as a vaccine adjuvant

    OpenAIRE

    Bode, Christian; Zhao, Gan; Steinhagen, Folkert; Kinjo, Takeshi; Klinman, Dennis M.

    2011-01-01

    Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs trigger cells that express Toll-like receptor 9 (including human plasmacytoid dendritic cells and B cells) to mount an innate immune response characterized by the production of Th1 and proinflammatory cytokines. When used as vaccine adjuvants, CpG ODNs improve the function of professional antigen-presenting cells and boost the generation of humoral and cellular vaccine-specific immune responses. These effects are optimi...

  15. Neo-adjuvant chemotherapy in advanced hypopharyngeal carcinoma

    OpenAIRE

    Joshi, P.; V Patil; Joshi, A; V Norohna; Chaturvedi, P.; Chaukar, D.; P Pai; D Nair; Juvekar, S; Agarwal, J. P.; A K D′cruz; Prabhash, K

    2013-01-01

    Objective: The aim of this retrospective study was to find out the role of neo-adjuvant chemotherapy (NACT) in changing the management and outcome of advanced hypopharyngeal cancer patients. Materials and Methods: This is a retrospective analysis of 59 treatment naïve, advanced hypopharyngeal cancer patients presenting to our tertiary care center from April 2010 to October 2011. NACT was given as two (platinum with taxane) or three drug with (platinum, taxane with 5-flurouracil [5 FU]) as 3 w...

  16. Recombinant human migration inhibitory factor has adjuvant activity.

    OpenAIRE

    Weiser, W Y; Pozzi, L M; Titus, R G; David, J R

    1992-01-01

    Recombinant human migration inhibitory factor (MIF), isolated through functional expression cloning in COS-1 cells, up-regulates expression of genes encoding HLA-DR and interleukin 1 beta (IL-1 beta) and elaboration of IL-1 beta by human monocyte-derived macrophages. Administration of soluble bovine serum albumin or human immunodeficiency virus 120-kDa glycoprotein (HIV gp120) to mice in the presence of recombinant MIF together with incomplete Freund's adjuvant induced a strong T-cell prolife...

  17. INTRASITE VANCOMYCIN POWDER AS A PROPHYLACTIC ADJUVANT IN LUMBAR FUSION

    OpenAIRE

    Jorge Álvaro González Ross; Alfredo Javier Moheno Gallardo; Eulalio Elizalde Martínez; José Manuel Pérez Atanasio; Ruth Martínez Martínez

    2016-01-01

    ABSTRACT Objective: To identify whether the use of prophylactic intrasite vancomycin as an adjuvant is a protective factor against deep tissue infection of the surgical site. Methods: Retrospective, descriptive, case-control study evaluating 210 patients, of whom 70 received intrasite vancomycin (case group) and 140 were controls. It was made a follow up for at least one year, reviewing the physical and electronic records. Data were tabulated in spreadsheets (Excel) including all variable...

  18. Controversies in the Adjuvant Therapy of Endometrial Cancer

    OpenAIRE

    Sheng-Mou Hsiao; Lin-Hung Wei

    2011-01-01

    Endometrial cancer is the most common malignancy of the female genital tract. Surgical treatment includes hysterectomy, bilateral salpingo-oophorectomy, and an appropriate staging procedure. Relapse of endometrial cancer may occur in patients with high risk factors, such as old age, grade 3 cancer, deep myometrial invasion, and papillary serous and clear cell types. In recent years, several randomized trials reported the results of adjuvant therapy for patients with high risk factors. Nonethe...

  19. Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

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    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.

  20. 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.

  1. Establishment of a Rat Adjuvant Arthritis-Interstitial Lung Disease Model

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    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.

  2. 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.

  3. Adjuvant chemotherapy prior to postoperative concurrent chemoradiotherapy for locoregionally advanced head and neck cancer

    International Nuclear Information System (INIS)

    Background and purpose: Induction chemotherapy prior to definitive concurrent chemoradiotherapy (CCRT) is a promising treatment option for unresectable head and neck cancer (HNC). In the postoperative setting, the efficacy of such an approach with adjuvant chemotherapy (AdjCT) followed by postoperative CCRT is unclear. Materials and methods: Forty-one postoperative patients with stage III-IV (M0) HNC enrolled on 3 consecutive phase II clinical trials were retrospectively analyzed. Twenty-five of the patients were treated on a protocol which included AdjCT with carboplatin and paclitaxel prior to postoperative CCRT (AdjCT group). Sixteen were treated on protocols with similar postoperative CCRT but without AdjCT (control group). CCRT consisted of paclitaxel, 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy. Results: After a median follow-up of 72 months, there were no locoregional failures (LRF) or distant metastases (DM) in the AdjCT group. In the control group, there were 2 LRF and 2 DM. The 5-year risk of disease recurrence was 0% in the AdjCT group, compared to 28.9% in the control group (p = 0.0074). No patients had disease progression during AdjCT, and all proceeded to postoperative CCRT without delay. Conclusions: Adjuvant chemotherapy after surgery followed by CCRT may be a treatment strategy associated with favorable disease outcomes in locoregionally advanced HNC. These results pose a hypothesis which warrants further investigation.

  4. Influence of Asian dust particles on immune adjuvant effects and airway inflammation in asthma model mice.

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    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.

  5. 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.

  6. [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. PMID:26469159

  7. Vitamin Supplementation as an Adjuvant Treatment for Alzheimer's Disease.

    Science.gov (United States)

    Bhatti, Adnan Bashir; Usman, Muhammad; Ali, Farhan; Satti, Siddique Akbar

    2016-08-01

    Alzheimer's Disease (AD) is a slowly progressing neurodegenerative disorder representing a major health concern worldwide. This disorder is characterised by progressive dementia and cognitive decline. The pathological hallmarks of AD include the presence of Aβ plaques and tau neurofibrils. Research has shown that oxidative stress represents a major risk factor associated with AD pathology. Accumulation of Aβ plaques and relative lack of antioxidant defence mechanisms, including cellular antioxidant enzymes and dietary antioxidants like vitamins, assist in the exacerbation of oxidative stress. Reactive Oxygen Species (ROS) produced as the result of oxidative stress, that increase structural and functional abnormalities in brain neurons, which then manifests as dementia and decline in cognition. Data from numerous epidemiological studies suggests that nutrition is one of the most important yet modifiable risk factors for AD. Since oxidative stress contributes a great deal in the development and progression of AD, anything that could attenuate oxidative stress would help in decreasing the prevalence and incidence of AD. There is increasing evidence that supports the use of different antioxidant as an adjuvant treatment for AD. Vitamins are one such antioxidant that can be used as an adjuvant in AD treatment. This paper will focus on the evidence, based on current literature, linking the use of vitamin supplementations as an adjuvant treatment for AD. PMID:27656493

  8. [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.

  9. 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.

  10. Generation of humoral immune responses to multi-allele PfAMA1 vaccines; effect of adjuvant and number of component alleles on the breadth of response.

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    Kwadwo A Kusi

    Full Text Available There is increasing interest in multi-allele vaccines to overcome strain-specificity against polymorphic vaccine targets such as Apical Membrane Antigen 1 (AMA1. These have been shown to induce broad inhibitory antibodies in vitro and formed the basis for the design of three Diversity-Covering (DiCo proteins with similar immunological effects. The antibodies produced are to epitopes that are shared between vaccine alleles and theoretically, increasing the number of component AMA1 alleles is expected to broaden the antibody response. A plateau effect could however impose a limit on the number of alleles needed to achieve the broadest specificity. Moreover, production cost and the vaccine formulation process would limit the number of component alleles. In this paper, we compare rabbit antibody responses elicited with multi-allele vaccines incorporating seven (three DiCos and four natural AMA1 alleles and three (DiCo mix antigens for gains in broadened specificity. We also investigate the effect of three adjuvant platforms on antigen specificity and antibody functionality. Our data confirms a broadened response after immunisation with DiCo mix in all three adjuvants. Higher antibody titres were elicited with either CoVaccine HT™ or Montanide ISA 51, resulting in similar in vitro inhibition (65-82% of five out of six culture-adapted P. falciparum strains. The antigen binding specificities of elicited antibodies were also similar and independent of the adjuvant used or the number of vaccine component alleles. Thus neither the four extra antigens nor adjuvant had any observable benefits with respect to specificity broadening, although adjuvant choice influenced the absolute antibody levels and thus the extent of parasite inhibition. Our data confirms the feasibility and potential of multi-allele PfAMA1 formulations, and highlights the need for adjuvants with improved antibody potentiation properties for AMA1-based vaccines.

  11. Radical hysterectomy with adjuvant radiotherapy versus radical radiotherapy for FIGO stage IIB cervical cancer

    International Nuclear Information System (INIS)

    The goal of this study was to compare treatment outcomes for Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical carcinoma patients receiving radical surgery followed by adjuvant postoperative radiotherapy versus radical radiotherapy. Medical records of FIGO stage IIB cervical cancer patients treated between July 2008 and December 2011 were retrospectively reviewed. A total of 148 patients underwent radical hysterectomy with pelvic lymph node dissection followed by adjuvant radiotherapy (surgery-based group). These patients were compared with 290 patients that received radical radiotherapy alone (RT-based group). Recurrence rates, progression-free survival (PFS), overall survival (OS), local control rates, and treatment-related complications were compared for these two groups. Similar rates of recurrence (16.89% vs. 12.41%, p = 0.200), PFS (log-rank, p = 0.211), OS (log-rank, p = 0.347), and local control rates (log-rank, p = 0.668) were observed for the surgery-based group and the RT-based group, respectively. Moreover, the incidence of acute grade 3–4 gastrointestinal reactions and late grade 3–4 lower limb lymphedema were significantly higher for the surgery-based group versus the RT-based group. Cox multivariate analyses found no significant difference in survival outcome between the two groups, and tumor diameter and histopathology were identified as significant prognostic factors for OS. Radical radiotherapy was associated with fewer treatment-related complications and achieved comparable survival outcomes for patients with FIGO stage IIB cervical cancer compared to radical hysterectomy followed by postoperative radiotherapy

  12. C-erbB-2 expression and benefit from adjuvant chemotherapy and radiotherapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Staal, O.; Sullivan, S.; Wingren, S.; Skoog, L.; Rutqvist, L.E.; Nordenskjoeld, B. [Karolinska Sjukhuset, Stockholm (Sweden); Carstensen, J.M. [Linkoeping Univ. (Sweden)

    1995-12-31

    Frozen tissue from primary tumours of 152 premenopausal breast cancer patients, who participated in a trial comparing radiotherapy with adjuvant chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil, CMF), was analysed for c-erbB-2 protein expression, measured by flow cytometry. The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 3.0 (95% confidence interval (CI) 1.1-7.8) for patients whose tumours showed high c-erbB-2 levels and 0.87 (95% CI 0.43-1.7) for those with tumours with low levels of c-erbB-2 protein. Patients with highly proliferative tumours that did not overexpress c-erbB-2 benefited most, in terms of survival, from CMF. In addition, we found an increased risk of locoregional recurrence for tumours overexpressing c-erbB-2 when radiotherapy was replaced by chemotherapy. (author).

  13. Green propolis phenolic compounds act as vaccine adjuvants, improving humoral and cellular responses in mice inoculated with inactivated vaccines

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    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.

  14. Adjuvant chemotherapy for ypT0N0M0 rectal cancer following chemoradiotherapy and total mesorectal excision.

    Science.gov (United States)

    Kainthla, Radhika; Huerta, Sergio

    2016-10-01

    The management of adenocarcinoma of the rectum is a dynamic field in oncology. The multidisciplinary approach to the management of this disease continues to evolve in each segment of its trimodality treatment. New scheduling regimens and radiosensitizing agents continue to emerge. Although total mesorectal excision continues to be the operation of choice for rectal cancers, what is done before and after surgery continues to evolve to maximize an ideal oncologic outcome with minimal morbidity. The achievement of a pathological complete response [pCR (i.e. ypT0N0)] in a fraction of patients undergoing neoadjuvant chemoradiation poses an interesting management dilemma. The cohort of patients who can achieve a pCR have superior oncologic outcomes compared to nonresponders. The present review addresses the need for adjuvant therapy in patients with a pCR. We discuss the evolution of the role of adjuvant therapy in patients with rectal cancer and the studies addressing the elimination of this strategy in all patients with rectal cancer with a goal of determining the current evidence that might result in the omission of adjuvant therapy for patients with ypT0N0 rectal cancer after chemoradiation and total mesorectal excision. PMID:27387144

  15. Triphala exhibits anti-arthritic effect by ameliorating bone and cartilage degradation in adjuvant-induced arthritic rats.

    Science.gov (United States)

    Kalaiselvan, Sowmiya; Rasool, MahaboobKhan

    2015-01-01

    The present study was aimed to investigate the anti-arthritic effect of triphala and its underlying mechanism on adjuvant-induced rat model. For comparison purpose, non-steroidal anti-inflammatory drug indomethacin was used. Arthritis was induced by intradermal injection of complete Freund's adjuvant (0.1 ml) into the right hind paw of the Wistar albino rats. Triphala (100 mg/kg body weight [bwt]) was administered intraperitoneally (from 11th to 20th day) after the arthritis induction. Arthritis induction increased the levels of reactive oxygen species (LPO and NO), elastase, and mRNA expression of pro-inflammatory cytokines (TNF-α, IL-β, IL-17, IL-6 and MCP-1), inflammatory marker enzymes (iNOS and COX-2), receptor activator of nuclear factor kappa-B ligand (RANKL), and transcription factors (NF-kB p65 and AP-1) in the paw tissues of rats. The levels of bone collagen were found to decrease with increased urinary constituents (hydroxyproline and total glycosaminoglycans) in arthritic rats. In addition, the immunohistochemistry analysis revealed increased expression of NF-kBp65 and COX-2 in the paw tissues of arthritic rats. However, administration of triphala significantly inhibited the biochemical and molecular alterations in adjuvant-induced arthritic rats compared to indomethacin (3 mg/kg bwt) as evidenced by the radiological and histopathological analysis. In conclusion, our results suggest that triphala administration ameliorate bone and cartilage degradation during rheumatoid arthritis. PMID:25942351

  16. 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.

  17. Establishment of a new quality control and vaccine safety test for influenza vaccines and adjuvants using gene expression profiling.

    Directory of Open Access Journals (Sweden)

    Haruka Momose

    Full Text Available 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.

  18. Development and application of next generation SE36 malaria vaccine formulated with a novel adjuvant: approach to travelers' vaccine.

    Science.gov (United States)

    Tougan, Takahiro; Ishii, Ken J; Horii, Toshihiro

    2013-01-01

    The SE36 antigen, derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Previous clinical trials indicated the protective efficacy of BK-SE36 malaria vaccine that is constituted of SE36 recombinant protein and aluminum hydroxide gel. In this study, we assessed the safety, immunogenicity and protective efficacy of SE36/AHG formulated with TLR9 ligand adjuvants K3 CpG oligodeoxyribonucleotides (CpG ODNs) (K3 ODN), D3 ODN or synthetic hemozoin, in two non-human primate models. SE36/AHG with or without each adjuvant was administrated to cynomolgus monkeys. A combination of TLR9 ligand adjuvant with SE36/AHG induced higher humoral and cellular immune response compared with SE36/AHG alone. The most effective TLR9 ligand, K3 ODN, was chosen for further vaccine trials in squirrel monkeys, in combination with SE36/AHG. All monkeys immunized SE36/AHG with K3 ODN effectively suppressed parasitemia and symptoms of malaria following challenge infection. Furthermore, no serious adverse events were observed. Our results show that the novel vaccine formulation of K3 ODN with SE36/AHG is safety, potent immunogenicity and efficacy in nonhuman primates. We are conducting the first in human clinical trials with this formulation. PMID:24189556

  19. 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.

  20. Application of the Western-based adjuvant online model to Korean colon cancer patients; a single institution experience

    International Nuclear Information System (INIS)

    Adjuvant Online (AOL) is web-accessible risk-assessment model that predicts the mortality and the benefits of adjuvant therapy. AOL has never been validated for Asian colon cancer patients. Using the Yonsei Tumor Registry database, patients who were treated within the Yonsei University Health System between 1990 and 2005 for T1-4, N0-2, and M0 colon cancer were included in the calculations for survival. Observed and predicted 5-year overall survival was compared for each patient. The median age of the study population of 1431 patients was 60 years (range, 15–87 years), and the median follow-up duration was 7.9 years (range, 0.06–19.8 years). The predicted 5-year overall survival rate (77.7%) and observed survival (79.5%) was not statistically different (95% Confidential interval, 76.3–81.5) in all patients. Predicted outcomes were within 95% confidential interval of observed survival in both stage II and III disease, including most demographic and pathologic subgroups. Moreover, AOL more accurately predicted OS for patients with stage II than stage III. AOL tended to offer reliable prediction for 5-year overall survival and could be used as a decision making tool for adjuvant treatment in Korean colon cancer patients whose prognosis is similar to other Asian patients

  1. 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.

  2. 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.

  3. 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

  4. Influence of Brucella abortus lipopolysaccharide as an adjuvant on the immunogenicity of HPV-16 L1VLP vaccine in mice.

    Science.gov (United States)

    Kianmehr, Zahra; Soleimanjahi, Hoorieh; Ardestani, Susan Kaboudanian; Fotouhi, Fatemeh; Abdoli, Asghar

    2015-04-01

    Brucella abortus lipopolysaccharide (LPS) has less toxicity and no pyrogenic properties in comparison with other bacterial LPS. It is a toll-like receptor 4 agonist and has been shown to have the potential use as a vaccine adjuvant. In this study, the immunostimulatory properties of LPS from smooth and rough strains of B. abortus (S19 and RB51) as adjuvants were investigated for the human papillomavirus type 16 (HPV16) L1 virus-like particles (L1VLPs) vaccines. C57BL/6 mice were immunized subcutaneously three times either with HPV-16 L1VLPs alone, or in combination with smooth LPS (S-LPS), rough LPS (R-LPS), aluminum hydroxide or a mixture of them as adjuvant. The humoral immunity was evaluated by measuring the specific and total IgG levels, and also the T-cell immune response of mice was evaluated by measuring different cytokines such as IFN-γ, TNF-α, IL-4, IL-10 and IL-17. Results showed that serum anti-HPV16 L1VLP IgG antibody titers was significantly higher in mice immunized with a combination of VLPs and R-LPS or S-LPS compared with other immunized groups. Co-administration of HPV-16 L1VLPs with R-LPS elicited the highest levels of splenocytes cytokines (IFN-γ, IL-4, IL-17 and TNF-α) and also effectively induced improvement of a Th1-type cytokine response characterized with a high ratio of IFN-γ/IL-10. The data indicate that B. abortus LPS particularly RB51-LPS enhances the immune responses to HPV-16 L1VLPs and suggests its potential as an adjuvant for the development of a potent prophylactic HPV vaccine and other candidate vaccines.

  5. Influence of Brucella abortus lipopolysaccharide as an adjuvant on the immunogenicity of HPV-16 L1VLP vaccine in mice.

    Science.gov (United States)

    Kianmehr, Zahra; Soleimanjahi, Hoorieh; Ardestani, Susan Kaboudanian; Fotouhi, Fatemeh; Abdoli, Asghar

    2015-04-01

    Brucella abortus lipopolysaccharide (LPS) has less toxicity and no pyrogenic properties in comparison with other bacterial LPS. It is a toll-like receptor 4 agonist and has been shown to have the potential use as a vaccine adjuvant. In this study, the immunostimulatory properties of LPS from smooth and rough strains of B. abortus (S19 and RB51) as adjuvants were investigated for the human papillomavirus type 16 (HPV16) L1 virus-like particles (L1VLPs) vaccines. C57BL/6 mice were immunized subcutaneously three times either with HPV-16 L1VLPs alone, or in combination with smooth LPS (S-LPS), rough LPS (R-LPS), aluminum hydroxide or a mixture of them as adjuvant. The humoral immunity was evaluated by measuring the specific and total IgG levels, and also the T-cell immune response of mice was evaluated by measuring different cytokines such as IFN-γ, TNF-α, IL-4, IL-10 and IL-17. Results showed that serum anti-HPV16 L1VLP IgG antibody titers was significantly higher in mice immunized with a combination of VLPs and R-LPS or S-LPS compared with other immunized groups. Co-administration of HPV-16 L1VLPs with R-LPS elicited the highest levels of splenocytes cytokines (IFN-γ, IL-4, IL-17 and TNF-α) and also effectively induced improvement of a Th1-type cytokine response characterized with a high ratio of IFN-γ/IL-10. The data indicate that B. abortus LPS particularly RB51-LPS enhances the immune responses to HPV-16 L1VLPs and suggests its potential as an adjuvant for the development of a potent prophylactic HPV vaccine and other candidate vaccines. PMID:25187406

  6. 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. PMID:25664993

  7. Review on adjuvant chemotherapy for rectal cancer - why do treatment guidelines differ so much?

    DEFF Research Database (Denmark)

    Poulsen, Laurids Ø; Qvortrup, Camilla; Pfeiffer, Per;

    2015-01-01

    /oxaliplatin. METHODS: 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. RESULTS: As regards patients treated with preoperative (chemo...... of adjuvant chemotherapy and if adjuvant colon cancer studies are considered transferrable to rectal cancer patients regardless of the molecular differences....

  8. Adjuvant radiotherapy for melanoma metastatic to axillary and inguinal nodes: Regional tumor control and late effects

    OpenAIRE

    Ahmed SK; Kottschade LA; Markovic SN; Garces YI; Foote RL

    2014-01-01

    Background: Adjuvant radiotherapy reduces nodal recurrence in metastatic melanoma. The purpose of this study was to examine the effects of adjuvant radiotherapy on in-field nodal control of melanoma metastatic to axillary and inguinal lymph nodes. Methods: The medical records of patients who received adjuvant radiotherapy from January 1, 2003, through December 31, 2011, at Mayo Clinic were reviewed. Results: In the 20 patients identified, the rates of 2-year overall survival, nodal control, a...

  9. Chitin, Chitosan, and Glycated Chitosan Regulate Immune Responses: The Novel Adjuvants for Cancer Vaccine

    OpenAIRE

    Xiaosong Li; Min Min; Nan Du; Ying Gu; Tomas Hode; Mark Naylor; Dianjun Chen; Nordquist, Robert E.; Chen, Wei R.

    2013-01-01

    With the development of cancer immunotherapy, cancer vaccine has become a novel modality for cancer treatment, and the important role of adjuvant has been realized recently. Chitin, chitosan, and their derivatives have shown their advantages as adjuvants for cancer vaccine. In this paper, the adjuvant properties of chitin and chitosan were discussed, and some detailed information about glycated chitosan and chitosan nanoparticles was also presented to illustrate the trend for future development.

  10. Vaccination of Atlantic cod (Gadus morhua L.) against atypical furunculosis using different adjuvants

    OpenAIRE

    Hamid, Lemia M.O

    2003-01-01

    In recent years increased attention has been focussed on fish vaccines and vaccination against diseases in farmed fish. In this study, efficacy and side effects of vaccination against atypical furunculosis in Atlantic cod (Gadus morhua L.) were studied in an experimental trial by using different adjuvants. The different adjuvanted vaccines were administered by intraperitoneal injection (i.p.) to Atlantic cod. The adjuvants used were CpG DNA, Aluminium hydroxide (Alhydrogel), an...

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

    OpenAIRE

    Mold, M; Shardlow, E; Exley, C.

    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. EVALUATION OF N-RATIO IN SELECTING PATIENTS FOR ADJUVANT CHEMORADIOTHERAPY AFTER D2-GASTRECTOMY

    OpenAIRE

    Wilson Luiz da COSTA JUNIOR; Felipe Jose Fernandez COIMBRA; Batista, Thales Paulo; RIBEIRO, Heber Salvador de Castro; DINIZ, Alessandro Landskron

    2013-01-01

    Context Whether adjuvant chemoradiotherapy may contribute to improve survival outcomes after D2-gastrectomy remains controvertial. Objective To explore the clinical utility of N-Ratio in selecting gastric cancer patients for adjuvant chemoradiotherapy after D2-gastrectomy. Methods A retrospective cohort study was carried out on gastric cancer patients who underwent D2-gastrectomy alone or D2-gastrectomy plus adjuvant chemoradiotherapy (INT-0116 protocol) at the Hospital A. C. Camargo from...

  13. 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.

  14. Evaluation of the efficacy of a new oil-based adjuvant ISA 61 VG FMD vaccine as a potential vaccine for cattle.

    Science.gov (United States)

    Khorasani, A; Madadgar, O; Soleimanjahi, H; Keyvanfar, H; Mahravani, H

    2016-01-01

    Foot-and-mouth disease is an important viral disease of cloven-hoofed animals. Inactivated whole particle virus vaccines are still widely used in prophylactic vaccination campaigns. The choice of adjuvant is a very important factor in enhancing immune responses and the efficacy of inactivated vaccines. Montanide ISA 61 VG is a new ready-to-use mineral oil-based adjuvant developed by SEPPIC Inc. (SEPPIC, France) with high-potential immune responses needed for clinical protection against FMD infection. In this study, we compared the efficacy of two FMD vaccines either formulated with the new oil-based adjuvant ISA 61 VG and saponin, or with aluminum hydroxide gel and saponin. Both vaccines contained the same antigen payloads of O2010/IR. Two groups of 15 naive cattle received a single vaccination with different doses (full dose, 1/3 dose and 1/9 dose) to calculate their PD50 (50% protective dose) after being challenged with the homologous virulent virus. The mean neutralizing antibody titer was determined at 0, 7, 14 and 21 days after vaccination, measured by a micro neutralization test. The new vaccine improved humoral immune responses by 19%, while inducing a higher geometric mean. The titer for neutralizing antibodies was 2.91 log10 compared to the alum-gel based adjuvant vaccine which was 2.44 log10 (P-value=0.1782). The new vaccine showed a PD50 value of 10.05 as compared to a PD50 value of 4.171, respectively. According to the results, the FMD vaccine formulated with the new oil adjuvant, ISA 61 VG, shows potential as an alternative vaccine for routine and emergency vaccinations in the FMD enzootic region. PMID:27656222

  15. 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.

  16. 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

  17. Influence of Adjuvant Therapy in Cancer Survivors on Endothelial Function and Skeletal Muscle Deoxygenation.

    Directory of Open Access Journals (Sweden)

    Austin K Ederer

    Full Text Available The cardiotoxic effects of adjuvant cancer treatments (i.e., chemotherapy and radiation treatment have been well documented, but the effects on peripheral cardiovascular function are still unclear. We hypothesized that cancer survivors i would have decreased resting endothelial function; and ii altered muscle deoxygenation response during moderate intensity cycling exercise compared to cancer-free controls. A total of 8 cancer survivors (~70 months post-treatment and 9 healthy controls completed a brachial artery FMD test, an index of endothelial-dependent dilation, followed by an incremental exercise test up to the ventilatory threshold (VT on a cycle ergometer during which pulmonary V̇O2 and changes in near-infrared spectroscopy (NIRS-derived microvascular tissue oxygenation (TOI, total hemoglobin concentration ([Hb]total, and muscle deoxygenation ([HHb] ≈ fractional O2 extraction were measured. There were no significant differences in age, height, weight, and resting blood pressure between cancer survivors and control participants. Brachial artery FMD was similar between groups (P = 0.98. During exercise at the VT, TOI was similar between groups, but [Hb]total and [HHb] were significantly decreased in cancer survivors compared to controls (P < 0.01 The rate of change for TOI (ΔTOIΔ/V̇O2 and [HHb] (Δ[HHb]/ΔV̇O2 relative to ΔV̇O2 were decreased in cancer survivors compared to controls (P = 0.02 and P = 0.03 respectively. In cancer survivors, a decreased skeletal muscle microvascular function was observed during moderate intensity cycling exercise. These data suggest that adjuvant cancer therapies have an effect on the integrated relationship between O2 extraction, V̇O2 and O2 delivery during exercise.

  18. The prognosis factor of adjuvant radiation therapy after surgery in uterine sarcomas

    Directory of Open Access Journals (Sweden)

    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

  19. Treg inducing adjuvants for therapeutic vaccination against chronic inflammatory diseases

    Directory of Open Access Journals (Sweden)

    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

  20. Combined effect of space radiation and adjuvants on mice in vivo

    Science.gov (United States)

    Sorokina, Svetlana; Zaichkina, Svetlana; Rozanova, Olga; Aptikaeva, Gella; Romanchenko, Sergei; Smirnova, Helene; Peleshko, Vladimir

    2012-07-01

    Recently we investigated the cytogenetic effects of low-dose-rate high-LET radiation on SHK mice in the radiation field behind the concrete shield of the Serpukhov accelerator with 70 GeV proton energy, that simulates the spectral and component composition of radiation fields formed in the conditions of high-altitude flights. It was found that low doses of high-LET irradiation led to an increase in the cytogenetic damage in mice which can be compared with level of spontaneous lesions. At the same time no decrease of cytogenetic damage was detected after irradiation with the challenging dose of 1.5 Gy, i. e., no adaptive response (AR) takes place in polychromatic erythrocytes (PCE) as opposed to low doses of chronic X-radiation. The goal of the present work was to determine if there is any influence of combined action of low doses of high-LET radiation and adjuvants on the cytogenetic damages and solid tumor growth in mice. Two-month-old SHK male mice were used. A search for potential adaptogens was performed among the adjuvants such as dibazol and calcium chloride. In each experiment, a group of animals was exposed to low doses of high-LET radiation and treated with dibazol or CaCl2 solutions after that mice were additionally irradiated with X-radiation according to the scheme of AR: 0.1 Gy + 1.5 Gy. After 28 h, the animals of all groups were killed by the cervical dislocation. Bone marrow specimens for calculating micronuclei (MN) in PCE were prepared by a conventional method with minor modifications. The influence of combined treatment of high-LET radiation and adjuvants on the growth of solid tumor of Ehrlich ascite carcinoma was estimated by measuring the size of the tumor at different times after the inoculation of ascitic cells into the femur. Our earlier study has shown that dibazol when used alone not only induced AR but also increased the magnitude of radiation AR when used in combination with low doses of X-radiation. In present work the obtained results

  1. Synthetic DNA Vaccines: Improved Vaccine Potency by Electroporation and Co-delivered Genetic Adjuvants

    Directory of Open Access Journals (Sweden)

    Seleeke eFlingai

    2013-11-01

    Full Text Available In recent years, DNA vaccines have undergone a number of technological advancements that have incited renewed interest and heightened promise in the field. Two such improvements are the use of genetically engineered cytokine adjuvants and plasmid delivery via in vivo electroporation (EP, the latter of which has been shown to increase antigen delivery by nearly 1000-fold compared to naked DNA plasmid delivery alone. Both strategies, either separately or in combination, have been shown to augment cellular and humoral immune responses in not only mice, but also in large animal models. These promising results, coupled with recent clinical trials that have shown enhanced immune responses in humans, highlight the bright prospects for DNA vaccines to address many human diseases.

  2. Effect of Feeding Status on Adjuvant Arthritis Severity, Cachexia, and Insulin Sensitivity in Male Lewis Rats

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    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.

  3. Should all patients with serous and clear cell endometrial carcinoma receive adjuvant chemotherapy?

    Science.gov (United States)

    Boren, Todd P; Miller, David S

    2010-11-01

    Uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) represent two rare subtypes that have an increased risk of recurrence and worse overall survival compared with the more common endometrioid endometrial cancers. Meaningful data in the form of prospective randomized trials is lacking for both advanced and early-stage UPSC and UCCC. Data extrapolated from prospective trials in advanced endometrioid endometrial cancer and retrospective trials on early-stage UPSC suggest that adjuvant platinum and taxane-based chemotherapy may provide a survival benefit for these patients. Future trials specifically examining UPSC and UCCC are needed to elucidate the optimal treatment regimen for these patients. Given the current data, the option of chemotherapy should be considered in treatment-planning discussions for all patients with UPSC and UCCC. PMID:21118038

  4. 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

  5. Long-term side effects of adjuvant breast cancer treatment

    OpenAIRE

    Buijs, Ciska

    2008-01-01

    Breast cancer is the most common malignancy in women. Breast cancer accounts for one-third of all cancers in females and 24% of the patients are younger than 55 years of age. More than 10% all Dutch women will develop breast cancer and 70-80% of all breast cancer patients will survive over 5 years. In the absence of distant metastases, patients receive loco-regional therapy with or without adjuvant systemic therapy. Loco-regional therapy consists of either a modified radical mastectomy, in so...

  6. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

    International Nuclear Information System (INIS)

    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. 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. 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. 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 full planned courses of chemotherapy. This is due to

  7. The Adjuvant Activity of Epimedium Polysaccharide-Propolis Flavone Liposome on Enhancing Immune Responses to Inactivated Porcine Circovirus Vaccine in Mice.

    Science.gov (United States)

    Fan, Yunpeng; Guo, Liwei; Hou, Weifeng; Guo, Chao; Zhang, Weimin; Ma, Xia; Ma, Lin; Song, Xiaoping

    2015-01-01

    Objectives. The adjuvant activity of Epimedium polysaccharide-propolis flavone liposome (EPL) was investigated in vitro and in vivo. Methods. In vitro, the effects of EPL at different concentrations on splenic lymphocytes proliferation and mRNA expression of IFN-γ and IL-6 were determined. In vivo, the adjuvant activities of EPL, EP, and mineral oil were compared in BALB/c mice through vaccination with inactivated porcine circovirus type 2 (PCV2) vaccine. Results. In vitro, EPL promoted lymphocytes proliferation and increased the mRNA expression of IFN-γ and IL-6, and the effect was significantly better than EP at all concentrations. In vivo, EPL significantly promoted the lymphocytes proliferation and the secretion of cytokines and improved the killing activity of NK cells, PCV2-specific antibody titers, and the proportion of T-cell subgroups. The effects of EPL were significantly better than EP and oil adjuvant at most time points. Conclusion. EPL could significantly improve both PCV2-specific cellular and humoral immune responses, and its medium dose had the best efficacy. Therefore, EPL would be exploited in an effective immune adjuvant for inactivated PCV2 vaccine. PMID:26612996

  8. Neo-adjuvant endocrine therapy in breast cancer%乳腺癌新辅助内分泌治疗进展

    Institute of Scientific and Technical Information of China (English)

    刘倩

    2011-01-01

    针对局部晚期乳腺癌患者,尤其是绝经后内分泌反应型且不能耐受化疗的群体,新辅助内分泌治疗不失为一种选择方案.第三代芳香化酶抑制剂为绝经后患者首选药物,因其疗效显著优于他莫昔芬.同比新辅助化疗,在病例选择得当的前提下,新辅助内分泌治疗可获得相似的短期获益,由于长时间随访结果较少,总体预后尚不清楚.%Nco-adjuvant endocrine therapy has provided opened new alternatives for locally advanced breast cancer, especially for patient groups such as the elderly, those who are not suited for chemotherapy, and those whose response may not be optimal. The latest generation of endocrine therapy for breast cancer,aromatase inhibitors, has proved superior to tamoxifen in terms of toxicity and efficacy in the adjuvant setting.Compared with neo-adjuvant chemotherapy, the appropriate patients to receive nco-adjuvant endocrine therapy can achieve similar short-term benefit. However, because of fewer long-term follow up results, the overall prognosis is not clear.

  9. In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay as a Predictor of Clinical Response to Fluorouracil-Based Adjuvant Chemotherapy in Stage II Colorectal Cancer

    Science.gov (United States)

    Kwon, Hye Youn; Kim, Im-kyung; Kang, Jeonghyun; Sohn, Seung-Kook; Lee, Kang Young

    2016-01-01

    Purpose We evaluated the usefulness of the in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) for prediction of clinical response to fluorouracil-based adjuvant chemotherapy in stage II colorectal cancer. Materials and Methods Tumor specimens of 86 patients with pathologically confirmed stage II colorectal adenocarcinoma were tested for chemosensitivity to fluorouracil. Chemosensitivity was determined by cell death rate (CDR) of drug-exposed cells, calculated by comparing the intracellular ATP level with that of untreated controls. Results Among the 86 enrolled patients who underwent radical surgery followed by fluorouracil-based adjuvant chemotherapy, recurrence was found in 11 patients (12.7%). The CDR ≥ 20% group was associated with better disease-free survival than the CDR < 20% group (89.4% vs. 70.1%, p=0.027). Multivariate analysis showed that CDR < 20% and T4 stage were poor prognostic factors for disease-free survival after fluorouracil-based adjuvant chemotherapy. Conclusion In stage II colorectal cancer, the in vitro ATP-CRA may be useful in identifying patients likely to benefit from fluorouracil-based adjuvant chemotherapy. PMID:26511802

  10. Effect of dendritic cell/cytokine-induced killer cell immunobiological cancer therapy combined with adjuvant chemotherapy in patients with triple-negative breast cancer

    Institute of Scientific and Technical Information of China (English)

    Ranran Zhang; Dongchu Ma; Xiaodong Xie; Wanqing Xie Co-first author; Tao Han; Yongye Liu; Zhaozhe Liu; Fang Guo; Yaling Han; Zhenyu Ding; Yinghui Sun

    2015-01-01

    Objective The aim of the present study was to investigate the ef ect of dendritic cel (DC)/cytokine-in-duced kil er cel (CIK) immunobiological cancer therapy in patients with triple-negative breast cancer (TNBC) who underwent adjuvant chemotherapy. Methods From January 2010 to October 2013, 120 patients with postoperative TNBC were recruited and included in the study. Patients were enrol ed in one of two groups according to whether they accepted DC/CIK immunobiological cancer therapy during adjuvant chemotherapy; the patients in the DC/CIK group underwent adjuvant chemotherapy combined with DC/CIK immunobiological cancer therapy, and the control group underwent adjuvant chemotherapy alone. When six cycles of adjuvant chemotherapy and six cycles of DC/CIK immunobiological cancer therapy had been completed, dif erences between the two groups with regard to quality of life (QoL), immunological indicators (CD3, CD4, CD8, and NK cel levels), disease-free survival (DFS), and side ef ects of chemotherapy and DC/CIK treatment were evaluated. Results In the DC/CIK group, the proportion of NK cel s and CD3+ and CD4+ T-cel subgroups significantly increased, and the proportion of CD8+ cel s decreased when they were compared before and after DC/CIK therapy (P Conclusion The DC/CIK treatment had potential benefits for patients with TNBC compared with the con-trol group, and was not associated with any obvious side ef ects. Therefore, DC/CIK therapy is a safe and ef ective method for the treatment of TNBC.

  11. A caprine herpesvirus 1 vaccine adjuvanted with MF59™ protects against vaginal infection and interferes with the establishment of latency in goats.

    Directory of Open Access Journals (Sweden)

    Mariarosaria Marinaro

    Full Text Available The immunogenicity and the efficacy of a beta-propiolactone-inactivated caprine herpesvirus 1 (CpHV-1 vaccine adjuvanted with MF59™ were tested in goats. Following two subcutaneous immunizations, goats developed high titers of CpHV-1-specific serum and vaginal IgG and high serum virus neutralization (VN titers. Peripheral blood mononuclear cells (PBMC stimulated in vitro with inactivated CpHV-1 produced high levels of soluble IFN-gamma and exhibited high frequencies of IFN-gamma producing cells while soluble IL-4 was undetectable. On the other hand, control goats receiving the inactivated CpHV-1 vaccine without adjuvant produced only low serum antibody responses. A vaginal challenge with virulent CpHV-1 was performed in all vaccinated goats and in naïve goats to assess the efficacy of the two vaccines. Vaginal disease was not detected in goats vaccinated with inactivated CpHV-1 plus MF59™ and these animals had undetectable levels of infectious challenge virus in their vaginal washes. Goats vaccinated with inactivated CpHV-1 in the absence of adjuvant exhibited a less severe disease when compared to naïve goats but shed titers of challenge virus that were similar to those of naïve goats. Detection and quantitation of latent CpHV-1 DNA in sacral ganglia in challenged goats revealed that the inactivated CpHV-1 plus MF59™ vaccine was able to significantly reduce the latent viral load when compared either to the naïve goats or to the goats vaccinated with inactivated CpHV-1 in the absence of adjuvant. Thus, a vaccine composed of inactivated CpHV-1 plus MF59™ as adjuvant was strongly immunogenic and induced effective immunity against vaginal CpHV-1 infection in goats.

  12. Esophagectomy for locally advanced esophageal cancer, followed by chemoradiotherapy and adjuvant chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Hung-Chang Liu; Yu-Jen Chen; Shih-Kai Hung; Charn-Jer Huang; Chung-Chu Chen; Ming-Jen Chen; Chun-Chao Chang; Cheng-Jeng Tai; Chi-Yuan Tzen; Li-Hua Lu

    2005-01-01

    AIM: To compare the efficacy and toxicity of a three-step combination therapy with post-operative radiation alone for locally advanced esophageal cancer.METHODS: Patients with T3-4 and N0-1 esophageal carcinoma from a number of institutions were non-randomly,prospectively enrolled in the study. All patients underwent single-stage curative en bloc esophagectomy. The patients were then assigned into one of two treatment groups based on treatment consisting of either post-operative concurrent chemoradiotherapy (CCRT) with weekly cisplatin 30 mg/m2 followed by systemic adjuvant chemotherapy (four monthly cycles of cisplatin 20 mg/m2 and 5-fiuorouracil 1 000 mg/m2 for five consecutive days),or, post-operative radiation alone. The radiotherapy dose was 55-60 Gy for all patients. Primary end-point of this study was to assess the per-protocol patients' improvement of overall survival benefit. Secondary end-point was designed to evaluate both the per-protocol and intent-to-treat patients' outcome of survival.RESULTS: A total of 60 patients (n = 30 per group) were enrolled in this study. The two groups were generally comparable for demographic characteristics and hematological and non-hematological toxicities. The CCRT with weekly cisplatin was well tolerated, with significantly better overall survival (30.9 mo vs 20.7 mo; 95% CI,27.5-36.4 vs15.2-26.1) and 3-year survival (70.0% vs 33.7%; P = 0.003). Low histological grade of tumor (P<0.001) was associated with favorable survival in these locally advanced patients.CONCLUSION: For locally advanced esophageal cancer,the combination of esophagectomy, post-operative CCRT with weekly cisplatin and systemic adjuvant chemotherapy is well tolerated and effective. A large-scale, prospective randomized trial of this regimen is in progress.

  13. Conjunctival Autograft Alone or Combined With Adjuvant Beta-Radiation? A Randomized Clinical Trial

    International Nuclear Information System (INIS)

    Purpose: To evaluate the effectiveness and safety of postoperative low single-dose of beta-irradiation (β-RT) in pterygium comparing conjunctival autograft (CAG) surgery with CAG plus adjuvant β-RT in a randomized clinical trial. Methods: This trial was designed as a prospective, randomized, single-center study. Surgery was performed in all cases according to the CAG technique. One hundred and eight pterygia were postoperatively randomized to CAG + β-RT or CAG alone. In the case of β-RT, a (90) Sr eye applicator was used to deliver 10 Gy to the sclera surface at a dose rate of between 200 and 250 cGy/min. After treatment, both an ophthalmologist and a radiation oncologist performed the follow-up examinations. The accumulated data were analyzed using a group sequential test. Results: Between February 2008 and September 2008, 116 eyes with primary pterygium were operated on according to the trial protocol. Adjuvant treatment was performed within 24 h postoperatively. Eight patients were lost to follow-up, resulting in 108 patients who could be analyzed. At a mean follow-up of 18 months (range, 8–33), in the 54 eyes randomized to receive CAG + β-RT, 5 relapses occurred compared with 12 recurrences in the 54 eyes in CAG, for a crude control rate of 90.8 % vs. 78%; p = 0.032, respectively. The treatment complications as hyperemia, total dehiscence of the autograft and dellen were significantly more frequent in the CAG (p < 0.05). The arm of β-RT resulted in better cosmetic results and improves of symptoms than CAG. Conclusions: A low single-dose of β-RT of 10 Gy after CAG surgery was a simple, effective, and safe treatment that reduced the risk of primary pterygium recurrence, improved symptoms after surgery, resulting in a better cosmetic effect than only CAG.

  14. Conjunctival Autograft Alone or Combined With Adjuvant Beta-Radiation? A Randomized Clinical Trial

    Energy Technology Data Exchange (ETDEWEB)

    Arruda Viani, Gustavo, E-mail: gusviani@gmail.com [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo (Brazil); Carrara Fonseca, Ellen [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo (Brazil); Department of Ophthalmology, Marilia Medical School, Marilia, Sao Paulo (Brazil); De Fendi, Ligia Issa [Department of Ophthalmology, Marilia Medical School, Marilia, Sao Paulo (Brazil); Melani Rocha, Eduardo [Department of Ophthalmology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto (Brazil)

    2012-03-01

    Purpose: To evaluate the effectiveness and safety of postoperative low single-dose of beta-irradiation ({beta}-RT) in pterygium comparing conjunctival autograft (CAG) surgery with CAG plus adjuvant {beta}-RT in a randomized clinical trial. Methods: This trial was designed as a prospective, randomized, single-center study. Surgery was performed in all cases according to the CAG technique. One hundred and eight pterygia were postoperatively randomized to CAG + {beta}-RT or CAG alone. In the case of {beta}-RT, a (90) Sr eye applicator was used to deliver 10 Gy to the sclera surface at a dose rate of between 200 and 250 cGy/min. After treatment, both an ophthalmologist and a radiation oncologist performed the follow-up examinations. The accumulated data were analyzed using a group sequential test. Results: Between February 2008 and September 2008, 116 eyes with primary pterygium were operated on according to the trial protocol. Adjuvant treatment was performed within 24 h postoperatively. Eight patients were lost to follow-up, resulting in 108 patients who could be analyzed. At a mean follow-up of 18 months (range, 8-33), in the 54 eyes randomized to receive CAG + {beta}-RT, 5 relapses occurred compared with 12 recurrences in the 54 eyes in CAG, for a crude control rate of 90.8 % vs. 78%; p = 0.032, respectively. The treatment complications as hyperemia, total dehiscence of the autograft and dellen were significantly more frequent in the CAG (p < 0.05). The arm of {beta}-RT resulted in better cosmetic results and improves of symptoms than CAG. Conclusions: A low single-dose of {beta}-RT of 10 Gy after CAG surgery was a simple, effective, and safe treatment that reduced the risk of primary pterygium recurrence, improved symptoms after surgery, resulting in a better cosmetic effect than only CAG.

  15. Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

    International Nuclear Information System (INIS)

    Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy

  16. European and Far East Mistletoes: Potential in Adjuvant Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    Uwe PF(U)LLER; Udo SCHUMACHER

    2008-01-01

    Semiparasitic plants, mistletoes, distributed in Europe and East-Asia mainly, China, Korea and Japan have long been recognised as therapeutic herbs. Since the 1920s, extracts from European mistletoe (Viscum album L) have been popular in Europe as an unconventional cancer treatment. These extracts have been used in adjuvant cancer therapy because their immunostimulatory, cytostatic/cytotoxic and DNA stabilising activities. The main biological activities are addressed to sugar binding proteins, the Mistletoe Lectins, and to micro proteins named viscotoxins. The mistletoe lectins are members of the family of toxic lectins and recognize sugars and glycoconjugates containing galactose and/or N-acetyl-galactosamine groups. In vitro and in vivo assays confLrm that the mistletoe lectins, isolated from the plant and compared with recombinant forms, play an important role as biologically active principles in mistletoe extracts. Limited experimental evidence indicates that other components like glycosides, polysaccharides, amines etc, may also have anticancer activity. Under discussion in Europe is the principal question of using holo plant extracts or single component lectin preparations: wild type iectins or recombinant ones in cancer therapy. Finally problems of preparation, characterization and standardization of commercial mistletoe preparations and evaluation of biological activities are discussed.%槲寄生属半寄生类植物,主要分布于欧洲及东亚,中国、韩国和日本很早以前就将其作为治疗用药.自上世纪二十年代,欧洲槲寄生提取物因具有免疫调节、抑制细胞生长/细胞毒素和稳定DNA,~性的作用,在欧洲被广泛应用于癌症的辅助治疗.对于槲寄生,其主要生物活性是糖粘合蛋白,槲寄生外源凝集素类和名为粘毒素的微蛋白.槲寄生外源凝集素类是毒性植物血凝素,糖和复合糖类(包括半乳糖和/或N-乙酰半乳糖胺)家族中的成员.活体内、外实验证实,

  17. Adjuvant Brachytherapy Removes Survival Disadvantage of Local Disease Extension in Stage IIIC Endometrial Cancer: A SEER Registry Analysis

    International Nuclear Information System (INIS)

    Purpose: To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. Methods and Materials: The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. Results: The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p <0.001). In patients with organ-confined Stage IIIC endometrial cancer, the 5-year OS rate was 50% for NAT, 64% for EBRT, and 67% for EBRT/BT. Again, adjuvant RT contributed to improved survival compared with NAT (p = 0.02). In patients with Stage IIIC endometrial cancer and direct tumor extension, the 5-year OS rate was 34% for NAT, 47% for EBRT, and 63% for EBRT/BT. RT improved OS compared with NAT (p <0.001). Also, in this high-risk subgroup, adding BT to EBRT was superior to EBRT alone (p = 0.002). Conclusion: Women with Stage IIIC endometrial cancer receiving adjuvant EBRT and EBRT/BT had improved OS compared with patients receiving NAT. When direct extension of the primary tumor was present, the addition of BT to EBRT was even more beneficial

  18. Innate Immune Signaling by, and Genetic Adjuvants for DNA Vaccination

    Directory of Open Access Journals (Sweden)

    Ken J. Ishii

    2013-07-01

    Full Text Available DNA vaccines can induce both humoral and cellular immune responses. Although some DNA vaccines are already licensed for infectious diseases in animals, they are not licensed for human use because the risk and benefit of DNA vaccines is still controversial. Indeed, in humans, the immunogenicity of DNA vaccines is lower than that of other traditional vaccines. To develop the use of DNA vaccines in the clinic, various approaches are in progress to enhance or improve the immunogenicity of DNA vaccines. Recent studies have shown that immunogenicity of DNA vaccines are regulated by innate immune responses via plasmid DNA recognition through the STING-TBK1 signaling cascade. Similarly, molecules that act as dsDNA sensors that activate innate immune responses through STING-TBK1 have been identified and used as genetic adjuvants to enhance DNA vaccine immunogenicity in mouse models. However, the mechanisms that induce innate immune responses by DNA vaccines are still unclear. In this review, we will discuss innate immune signaling upon DNA vaccination and genetic adjuvants of innate immune signaling molecules.

  19. Innate Immune Signaling by, and Genetic Adjuvants for DNA Vaccination.

    Science.gov (United States)

    Kobiyama, Kouji; Jounai, Nao; Aoshi, Taiki; Tozuka, Miyuki; Takeshita, Fumihiko; Coban, Cevayir; Ishii, Ken J

    2013-01-01

    DNA vaccines can induce both humoral and cellular immune responses. Although some DNA vaccines are already licensed for infectious diseases in animals, they are not licensed for human use because the risk and benefit of DNA vaccines is still controversial. Indeed, in humans, the immunogenicity of DNA vaccines is lower than that of other traditional vaccines. To develop the use of DNA vaccines in the clinic, various approaches are in progress to enhance or improve the immunogenicity of DNA vaccines. Recent studies have shown that immunogenicity of DNA vaccines are regulated by innate immune responses via plasmid DNA recognition through the STING-TBK1 signaling cascade. Similarly, molecules that act as dsDNA sensors that activate innate immune responses through STING-TBK1 have been identified and used as genetic adjuvants to enhance DNA vaccine immunogenicity in mouse models. However, the mechanisms that induce innate immune responses by DNA vaccines are still unclear. In this review, we will discuss innate immune signaling upon DNA vaccination and genetic adjuvants of innate immune signaling molecules.

  20. Adjuvant chemoradiotherapy for adenocarcinoma of the stomach. A new progress?

    International Nuclear Information System (INIS)

    Frequency of local and distant failures after gastrectomy has led to extended lymph nodes dissection to obtain a better locoregional control. However, five year survival rates were not significantly different between patients undergoing D2 and D1 lymphadenectomy, and higher morbidity and post operative deaths were reported in large randomized trials (respectively 25% vs 48% and 4 vs 13%). Additionally, several met-analysis failed to demonstrate a significant survival advantage with adjuvant chemotherapy. The results of the first trial demonstrating one advantage to adjuvant post-operative chemoradiotherapy should modify the standard care. Disease free and overall survival after surgery alone and after surgery and concurrent chemoradiotherapy were respectively 31% vs 48% and 41% vs 50%. The inter-group trial demonstrate that better local control improve survival if radiation fields include stamps, tumour bed, proximal nodal chains and nodes corresponding to D2 extended lymph nodes dissection. Treatment was feasible with few severe toxic effects (1%). Of the 281 patients, 17% stopped treatment because toxic effects. Technical modalities of radiotherapy and post-operative nutrition support which are critical points of interest for this treatment, are also discussed. (authors)

  1. Effects and mechanisms of Cryptotanshinone on rats with adjuvant arthritis

    Institute of Scientific and Technical Information of China (English)

    ZHENG Fu-lin; CHANG Yan; JIA Xiao-yi; HUANG Min; WEI Wei

    2011-01-01

    Background Cryptotanshinone (CT) is the major active constituent of Salvia miltiorrhiza Bunge.The present study was carried out to investigate the effects of CT on rats with adjuvant arthritis (AA).Methods AA was induced by the metatarsal footpad injection with complete Freund's adjuvant in male Sprague-Dawley rats.The secondary inflammatory reaction was evaluated by hind paw swelling and the polyarthritis index.Activity of interleukin-1 (IL-1) was detected by the concanavalin A-induced thymocytes proliferation assay.The lymphocytes proliferation and IL-2 production were assayed by 3-(4,5-2dimethylthiazal-2yl)2,5-diphenyltetrazoliumbromide (MIT) and activated mouse splenocytes proliferation,respectively.Results Intragastric administration of CT (50 and 100 mg/kg) significantly decreased secondary inflammatory reactions and increased the spleen and thymus index.There was a marked immunologic and inflammatory response in the AA model,which was accompanied by the decrease of thymocyte proliferation and IL-2 production as well as the increase of IL-1 production.CT apparently enhanced thymocyte proliferation and decreased IL-1 production in AA rats.Conclusion These results indicate that CT may exert its anti-inflammatory and immunoregulatory effects through inhibiting lymphocyte proliferation and production of pro-inflammatory mediators.

  2. Preparation and evaluation of functional foods in adjuvant arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Al-Okbi, S. Y.; Mohamed, D. A.

    2012-07-01

    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 functional foods containing such bioactive fractions separately or in combination and to evaluate them in adjuvant arthritis in rats, study the stability of bioactive ingredients and evaluate their sensory properties. The studied biochemical parameters were erythrocyte sedimentation rate, erythrocyte superoxide dismutase, glutathione peroxidase and plasma copper, zinc and interlukin 2. Nutritional parameters, including body weight gain, food intake and food efficiency ratio were monitored during the feeding of the functional foods. The bioactive ingredients assessed were total phenolic contents and fatty acids. The results showed improvement in the biochemical parameters, body weight gain and food efficiency ratio of arthritic rats fed on the functional foods with different degrees. All the prepared functional foods were sensory accepted. The active ingredients showed stability during storage. In conclusion, all the tested functional foods showed promising antiinflammatory activity and were determined to be acceptable through sensory evaluation which means that their potential beneficial use as dietary supplements in rheumatoid arthritis patients may be recommended. (Author) 42 refs.

  3. [Group sports as adjuvant therapy for patients with atopic eczema].

    Science.gov (United States)

    Salzer, B; Schuch, S; Rupprecht, M; Hornstein, O P

    1994-11-01

    The therapeutic value of regular physical exercise for patients with atopic eczema (AE) and other chronic inflammatory dermatoses has not yet been investigated systematically. At our institution an adjuvant group sports programme for voluntary inpatients has been in place for 3 years. Using a standardized questionnaire we found positive psychological influences of this program on the patients' mood and psychosocial wellbeing. Since most dermatologists, however, regard sweating as detrimental for patients with AE, we studied the impact of regular sports activities on the skin condition of AE-patients otherwise subdued to usual dermatotherapy (yet without corticosteroids) by aid of a standardized symptomscore system. Thirty inpatients with AE participated regularly in the sports programme, another 30 inpatients with AE (the control group) did not. The skin condition improved similarly the two groups over the study period of about 3 weeks. Cutaneous thermoregulation (with one arm in a 41 degrees C water bath as thermic stimulus) was examined in patients with AE before and after the study period. While many AE patients initially showed paradoxical, i.e. decreasing, skin temperature in the contralateral arm, after 3 weeks of physical training most of the participants had normalized consensual, i.e. increased, temperature reaction to the same warmth exposure. The conclusion is drawn that regular sports may be of adjuvant therapeutic value in patients suffering from AE, except in the acute stages of the disease. PMID:7822198

  4. Adjuvant radiation therapy in metastatic lymph nodes from melanoma

    International Nuclear Information System (INIS)

    To analyze the outcome after adjuvant radiation therapy with standard fractionation regimen in metastatic lymph nodes (LN) from cutaneous melanoma. 86 successive patients (57 men) were treated for locally advanced melanoma in our institution. 60 patients (69%) underwent LN dissection followed by radiation therapy (RT), while 26 patients (31%) had no radiotherapy. The median number of resected LN was 12 (1 to 36) with 2 metastases (1 to 28). Median survival after the first relapse was 31.8 months. Extracapsular extension was a significant prognostic factor for regional control (p = 0.019). Median total dose was 50 Gy (30 to 70 Gy). A standard fractionation regimen was used (2 Gy/fraction). Median number of fractions was 25 (10 to 44 fractions). Patients were treated with five fractions/week. Patients with extracapsular extension treated with surgery followed by RT (total dose ≥50 Gy) had a better regional control than patients treated by surgery followed by RT with a total dose <50 Gy (80% vs. 35% at 5-year follow-up; p = 0.004). Adjuvant radiotherapy was able to increase regional control in targeted sub-population (LN with extracapsular extension)

  5. Alginate Nanoparticles as a Promising Adjuvant and Vaccine Delivery System

    Directory of Open Access Journals (Sweden)

    F Sarei

    2013-01-01

    Full Text Available During last decades, diphtheria has remained as a serious disease that still outbreaks and can occur worldwide. Recently, new vaccine delivery systems have been developed by using the biodegradable and biocompatible polymers such as alginate. Alginate nanoparticles as a carrier with adjuvant and prolong release properties that enhance the immunogenicity of vaccines. In this study diphtheria toxoid loaded nanoparticles were prepared by ionic gelation technique and characterized with respect to size, zeta potential, morphology, encapsulation efficiency, release profile, and immunogenicity. Appropriate parameters (calcium chloride and sodium alginate concentration, homogenization rate and homogenization time redounded to the formation of suitable nanoparticles with a mean diameter of 70±0.5 nm. The loading studies of the nanoparticles resulted in high loading capacities (>90% and subsequent release studies showed prolong profile. The stability and antigenicity of toxoid were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and ouchterlony test and proved that the encapsulation process did not affect the antigenic integrity and activity. Guinea pigs immunized with the diphtheria toxoid-loaded alginate nanoparticles showed highest humoral immune response than conventional vaccine. It is concluded that, with regard to the desirable properties of nanoparticles and high immunogenicity, alginate nanoparticles could be considered as a new promising vaccine delivery and adjuvant system.

  6. Characterization of Immune Responses to an Inactivated Avian Influenza Virus Vaccine Adjuvanted with Nanoparticles Containing CpG ODN.

    Science.gov (United States)

    Singh, Shirene M; Alkie, Tamiru N; Abdelaziz, Khaled Taha; Hodgins, Douglas C; Novy, Anastasia; Nagy, Éva; Sharif, Shayan

    2016-06-01

    Avian influenza virus (AIV), a mucosal pathogen, gains entry into host chickens through respiratory and gastrointestinal routes. Most commercial AIV vaccines for poultry consist of inactivated, whole virus with adjuvant, delivered by parenteral administration. Recent advances in vaccine development have led to the application of nanoparticle emulsion delivery systems, such as poly (d,l-lactic-co-glycolic acid) (PLGA) nanoparticles to enhance antigen-specific immune responses. In chickens, the Toll-like receptor 21 ligand, CpG oligodeoxynucleotides (ODNs), have been demonstrated to be immunostimulatory. The objective of this study was to compare the adjuvant potential of CpG ODN 2007 encapsulated in PLGA nanoparticles with nonencapsulated CpG ODN 2007 when combined with a formalin-inactivated H9N2 virus, through intramuscular and aerosol delivery routes. Chickens were vaccinated at days 7 and 21 posthatch for the intramuscular route and at days 7, 21, and 35 for the aerosol route. Antibody-mediated responses were evaluated weekly in sera and lacrimal secretions in specific pathogen-free chickens. The results indicate that nonencapsulated CpG ODN 2007 in inactivated AIV vaccines administered by the intramuscular route generated higher antibody responses compared to the encapsulated CpG ODN 2007 formulation by the same route. Additionally, encapsulated CpG ODN 2007 in AIV vaccines administered by the aerosol route elicited higher mucosal responses compared to nonencapsulated CpG ODN 2007. Future studies may be aimed at evaluating protective immune responses induced with PLGA encapsulation of AIV and adjuvants. PMID:27077969

  7. Unraveling molecular signatures of immunostimulatory adjuvants in the female genital tract through systems biology.

    Directory of Open Access Journals (Sweden)

    Madelene Lindqvist

    Full Text Available Sexually transmitted infections (STIs unequivocally represent a major public health concern in both industrialized and developing countries. Previous efforts to develop vaccines for systemic immunization against a large number of STIs in humans have been unsuccessful. There is currently a drive to develop mucosal vaccines and adjuvants for delivery through the genital tract to confer protective immunity against STIs. Identification of molecular signatures that can be used as biomarkers for adjuvant potency can inform rational development of potent mucosal adjuvants. Here, we used systems biology to study global gene expression and signature molecules and pathways in the mouse vagina after treatment with two classes of experimental adjuvants. The Toll-like receptor 9 agonist CpG ODN and the invariant natural killer T cell agonist alpha-galactosylceramide, which we previously identified as equally potent vaginal adjuvants, were selected for this study. Our integrated analysis of genome-wide transcriptome data determined which signature pathways, processes and networks are shared by or otherwise exclusive to these 2 classes of experimental vaginal adjuvants in the mouse vagina. To our knowledge, this is the first integrated genome-wide transcriptome analysis of the effects of immunomodulatory adjuvants on the female genital tract of a mammal. These results could inform rational development of effective mucosal adjuvants for vaccination against STIs.

  8. Antibody response in silver catfish (Rhamdia quelen) immunized with a model antigen associated with different adjuvants.

    Science.gov (United States)

    Pavan, T R; Di Domenico, J; Kirsten, K S; Nied, C O; Frandoloso, R; Kreutz, L C

    2016-07-25

    Adjuvants are essential to boost the immune response to inoculated antigen and play a central role in vaccine development. In this study, we investigated the efficacy of several adjuvants in the production of anti-bovine serum albumin (BSA) antibodies in silver catfish. Two hundred and seventy juvenile silver catfish (60-80 g) of both sexes were intraperitoneally vaccinated with BSA (200 µg/fish) alone or mixed to the following adjuvants: Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIA), aluminum hydroxide (AlOH), Montanide, four types of cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs) and three concentrations of β-glucan, and the immune enhancing property was evaluated by measuring anti-BSA antibodies in blood samples at biweekly intervals. Our results demonstrated that CpGs ODNs and β-glucan were as effective as classical adjuvants (FCA, FIA, AlOH and Montanide) in promoting anti-BSA antibodies and that the kinetics of antibody production induced by all adjuvants used in our study had a similar trend to that observed in other fish species, with a peak at 28 days post-vaccination. These results may be useful for the selection of adjuvants for vaccine formulation intended for silver catfish and for the development of vaccine and vaccination strategies to other fish species. PMID:27464022

  9. Aluminium based adjuvants and their effects on mitochondria and lysosomes of phagocytosing cells.

    Science.gov (United States)

    Ohlsson, Lars; Exley, Christopher; Darabi, Anna; Sandén, Emma; Siesjö, Peter; Eriksson, Håkan

    2013-11-01

    Aluminium oxyhydroxide, Al(OH)3 is one of few compounds approved as an adjuvant in human vaccines. However, the mechanism behind its immune stimulating properties is still poorly understood. In vitro co-culture of an aluminium adjuvant and the human monocytic cell line THP-1 resulted in reduced cell proliferation. Inhibition occurred at concentrations of adjuvant several times lower than would be found at the injection site using a vaccine formulation containing an aluminium adjuvant. Based on evaluation of the mitochondrial membrane potential, THP-1 cells showed no mitochondrial rupture after co-culture with the aluminium adjuvant, instead an increase in mitochondrial activity was seen. The THP-1 cells are phagocytosing cells and after co-culture with the aluminium adjuvant the phagosomal pathway was obstructed. Primary or early phagosomes mature into phagolysosomes with an internal pH of 4.5 - 5 and carry a wide variety of hydrolysing enzymes. Co-culture with the aluminium adjuvant yielded a reduced level of acidic vesicles and cathepsin L activity, a proteolytic enzyme of the phagolysosomes, was almost completely inhibited. THP-1 cells are an appropriate in vitro model in order to investigate the mechanism behind the induction of a phagocytosing antigen presenting cell into an inflammatory cell by aluminium adjuvants. Much information will be gained by investigating the phagosomal pathway and what occurs inside the phagosomes and to elucidate the ultimate fate of phagocytosed aluminium particles.

  10. 75 FR 66766 - NIAID Blue Ribbon Panel Meeting on Adjuvant Discovery and Development

    Science.gov (United States)

    2010-10-29

    ... knowledge and capabilities, and defines NIAID's goals for the continued discovery, development and... HUMAN SERVICES NIAID Blue Ribbon Panel Meeting on Adjuvant Discovery and Development Notice is hereby... discovery, development and clinical evaluation of adjuvants for use with preventive vaccines. NIAID...

  11. Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer

    DEFF Research Database (Denmark)

    Appel, Jon M; Zerahn, Bo; Møller, Susanne;

    2012-01-01

    Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment....

  12. Aluminum hydroxide adjuvant differentially activates the three complement pathways with major involvement of the alternative pathway

    DEFF Research Database (Denmark)

    Güven, Esin; Duus, Karen; Laursen, Inga;

    2013-01-01

    Al(OH)3 is the most common adjuvant in human vaccines, but its mode of action remains poorly understood. Complement involvement in the adjuvant properties of Al(OH)3 has been suggested in several reports together with a depot effect. It is here confirmed that Al(OH)3 treatment of serum depletes c...

  13. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity.

    Directory of Open Access Journals (Sweden)

    Martin Kreutz

    Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

  14. Cell Recruitment and Cytokines in Skin Mice Sensitized with the Vaccine Adjuvants: Saponin, Incomplete Freund’s Adjuvant, and Monophosphoryl Lipid A

    Science.gov (United States)

    Vitoriano-Souza, Juliana; Moreira, Nádia das Dores; Teixeira-Carvalho, Andréa; Carneiro, Cláudia Martins; Siqueira, Fernando Augusto Mathias; Vieira, Paula Melo de Abreu; Giunchetti, Rodolfo Cordeiro; Moura, Sandra Aparecida de Lima; Fujiwara, Ricardo Toshio; Melo, Maria Norma; Reis, Alexandre Barbosa

    2012-01-01

    Vaccine adjuvants are substances associated with antigens that are fundamental to the formation of an intense, durable, and fast immune response. In this context, the use of vaccine adjuvants to generate an effective cellular immune response is crucial for the design and development of vaccines against visceral leishmaniasis. The objective of this study was to evaluate innate inflammatory response induced by the vaccine adjuvants saponin (SAP), incomplete Freund’s adjuvant (IFA), and monophosphoryl lipid A (MPL). After a single dose of adjuvant was injected into the skin of mice, we analyzed inflammatory reaction, selective cell migration, and cytokine production at the injection site, and inflammatory cell influx in the peripheral blood. We found that all vaccine adjuvants were able to promote cell recruitment to the site without tissue damage. In addition, they induced selective migration of neutrophils, macrophages, and lymphocytes. The influx of neutrophils was notable at 12 h in all groups, but at other time points it was most evident after inoculation with SAP. With regard to cytokines, the SAP led to production of interleukin (IL)-2, IL-6, and IL-4. IFA promoted production of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-6, IL-17, IL-4, and IL-10. We also observed that MPL induced high production of IL-2, TNF-α, and IFN-γ, in addition to IL-6, IL-17, and IL-10. In peripheral blood, values of certain cell populations in the local response changed after stimulation. Our data demonstrate that the three vaccine adjuvants stimulate the early events of innate immune response at the injection site, suggesting their ability to increase the immunogenicity of co-administered antigens. Moreover, this work provides relevant information about elements of innate and acquired immune response induced by vaccine adjuvants administered alone. PMID:22829882

  15. Quality of adjuvant CMF chemotherapy for node-positive primary breast cancer : a population-based study

    NARCIS (Netherlands)

    Schaapveld, M; de Vries, EGE; van der Graaf, WTA; Otter, R; Willemse, PHB

    2004-01-01

    Purpose: Adjuvant 'classical' oral cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) has long been the mainstay of adjuvant chemotherapy for premenopausal breast cancer patients. The Comprehensive Cancer Center North Netherlands (CCCN) breast cancer working group performed a retrospective aud

  16. Preliminary results of capecitabine metronomic chemotherapy in operable triple-negative breast cancer after standard adjuvant therapy – A single-arm phase II study

    Directory of Open Access Journals (Sweden)

    Hanan Shawky

    2014-12-01

    Conclusion: One year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy, is active and well-tolerated in TNBC patients previously treated with standard adjuvant chemotherapy.

  17. Pseudo-Mannosylated DC-SIGN Ligands as Potential Adjuvants for HIV Vaccines

    Directory of Open Access Journals (Sweden)

    Angela Berzi

    2014-01-01

    Full Text Available The development of new and effective adjuvants may play a fundamental role in improving HIV vaccine efficacy. New classes of vaccine adjuvants activate innate immunity receptors, notably toll like receptors (TLRs. Adjuvants targeting the C-Type lectin receptor DC-SIGN may be alternative or complementary to adjuvants based on TRL activation. Herein we evaluate the ability of the glycomimetic DC-SIGN ligand Polyman 19 (PM 19 to modulate innate immune responses. Results showed that PM 19 alone, or in combination with TLR agonists, induces the expression of cytokines, β chemokines and co-stimulatory molecules that may, in turn, modulate adaptive immunity and exert anti-viral effects. These results indicate that the suitability of this compound as a vaccine adjuvant should be further evaluated.

  18. Adjuvant Whole Brain Radiotherapy: Strong Emotions Decide But Rational Studies Are Needed

    International Nuclear Information System (INIS)

    Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival

  19. A synthetic adjuvant to enhance and expand immune responses to influenza vaccines.

    Directory of Open Access Journals (Sweden)

    Rhea N Coler

    Full Text Available Safe, effective adjuvants that enhance vaccine potency, including induction of neutralizing Abs against a broad range of variant strains, is an important strategy for the development of seasonal influenza vaccines which can provide optimal protection, even during seasons when available vaccines are not well matched to circulating viruses. We investigated the safety and ability of Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE, a synthetic Toll-like receptor (TLR4 agonist formulation, to adjuvant Fluzone® in mice and non-human primates. The GLA-SE adjuvanted Fluzone vaccine caused no adverse reactions, increased the induction of T helper type 1 (T(H1-biased cytokines such as IFNγ, TNF and IL-2, and broadened serological responses against drifted A/H1N1 and A/H3N2 influenza variants. These results suggest that synthetic TLR4 adjuvants can enhance the magnitude and quality of protective immunity induced by influenza vaccines.

  20. Haemolytic activities of plant saponins and adjuvants. Effect of Periandra mediterranea saponin on the humoral response to the FML antigen of Leishmania donovani.

    Science.gov (United States)

    Santos, W R; Bernardo, R R; Peçanha, L M; Palatnik, M; Parente, J P; Palatnik de Sousa, C B

    1997-06-01

    An 87.7% (P saponin combined to the fucose-mannose ligand of Leishmania donovani (FML). However, an undesirable haemolytic effect was described for several saponins. Aiming to improve the formulation with FML/saponin, we comparatively analysed the haemolytic potential of recently characterized plant saponins and currently used adjuvants. The haemolytic activity of steroidic saponins from Agave sisalana; Smilax officinalis as well as commercial saponin (Riedel De Haën's), was higher than that of triterpenoid ones (Bredemeyera floribunda; Periandra mediterranea) and the Freund's complete adjuvant. The concentration resulting in 50% haemolysis was 500 micrograms ml-1 for aluminum hydroxide. The low haemolytic effect of P. mediterranea saponin was abolished by removal of its glycidic moiety and its sapogenin fraction as well as the Freund's Incomplete Adjuvant were non-haemolytic within this range. Furthermore, the adjuvant effect of three doses of P. mediterranea saponin injected with the FML antigen of L. donovani, was assayed in mice, either by the intraperitoneal (i.p.) or the subcutaneous (s.c.) route. The anti-FML IgG antibody levels increased and detectable levels were observed up to 3 months in the s.c. group. The response was expanded in both groups after an injection with a fourth vaccine dose. The IgG response showed increased levels of IgG2a only in the i.p. group, while IgG2b and IgG1 but not IgG3 antibodies were higher than controls in both groups. In conclusion, the results suggest that the recently described triterpenoid fractions of P. mediterranea can be safely used as adjuvant with low or non-haemolytic effect.

  1. CD133 expression is not an independent prognostic factor in stage II and III colorectal cancer but may predict the better outcome in patients with adjuvant therapy

    International Nuclear Information System (INIS)

    Cancer stem cells (CSCs) are notorious for their capacity of tumor progression, metastasis or resistance to chemo-radiotherapy. However, the undisputed role of cancer stem marker, CD133, in colorectal cancers (CRCs) is not clear yet. We assessed 271 surgically-resected stage II and III primary CRCs with (171) and without (100) adjuvant therapy after surgery. CD133 expression was analyzed by immunohistochemical (IHC) staining and real-time RT-PCR. CD133 promoter methylation was quantified by pyrosequencing. The CD133 IHC expression was significantly correlated with mRNA expression (p=0.0257) and inversely correlated with the promoter methylation (p=0.0001). CD133 was expressed more frequently in rectal cancer (p=0.0035), and in moderately differentiated tumors (p=0.0378). In survival analysis, CD133 expression was not significantly correlated with overall survival (OS) (p=0.9689) as well as disease-free survival (DFS) (p=0.2103). However, CD133+ tumors were significantly associated with better OS in patients with adjuvant therapy compared to those without adjuvant therapy (p<0.0001, HR 0.125, 95% CI 0.052-0.299). But the patients with CD133- tumors did not show any significant difference of survival according to adjuvant therapy (p=0.055, HR 0.500, 95% CI 0.247-1.015). In stage II and III CRCs, CD133 IHC expression may signify the benefit for adjuvant therapy although it is not an independent prognostic factor

  2. Subcomponent vaccine based on CTA1-DD adjuvant with incorporated UreB class II peptides stimulates protective Helicobacter pylori immunity.

    Directory of Open Access Journals (Sweden)

    John G Nedrud

    Full Text Available A mucosal vaccine against Helicobacter pylori infection could help prevent gastric cancers and peptic ulcers. While previous attempts to develop such a vaccine have largely failed because of the requirement for safe and effective adjuvants or large amounts of well defined antigens, we have taken a unique approach to combining our strong mucosal CTA1-DD adjuvant with selected peptides from urease B (UreB. The protective efficacy of the selected peptides together with cholera toxin (CT was first confirmed. However, CT is a strong adjuvant that unfortunately is precluded from clinical use because of its toxicity. To circumvent this problem we have developed a derivative of CT, the CTA1-DD adjuvant, that has been found safe in non-human primates and equally effective compared to CT when used intranasally. We genetically fused the selected peptides into the CTA1-DD plasmid and found after intranasal immunizations of Balb/c mice using purified CTA1-DD with 3 copies of an H. pylori urease T cell epitope (CTA1-UreB3T-DD that significant protection was stimulated against a live challenge infection. Protection was, however, weaker than with the gold standard, bacterial lysate+CT, but considering that we only used a single epitope in nanomolar amounts the results convey optimism. Protection was associated with enhanced Th1 and Th17 immunity, but immunizations in IL-17A-deficient mice revealed that IL-17 may not be essential for protection. Taken together, we have provided evidence for the rational design of an effective mucosal subcomponent vaccine against H. pylori infection based on well selected protective epitopes from relevant antigens incorporated into the CTA1-DD adjuvant platform.

  3. Comparison between a conventional subunit vaccine and the MF59-adjuvanted subunit influenza vaccine in the elderly: an evaluation of the safety, tolerability and immunogenicity.

    Science.gov (United States)

    Sindoni, D; La Fauci, V; Squeri, R; Cannavò, G; Bacilieri, S; Panatto, D; Gasparini, R; Amicizia, D

    2009-06-01

    The objective of this study was to evaluate and compare the safety, tolerability and immunogenicity for two seasonal influenza subunit vaccines, one with MF59 adjuvant (Fluad) and one without an adjuvant (Agrippal). A total of 195 subjects aged > or = 65 years were enrolled to receive one dose of vaccine intramuscularly, 96 were vaccinated with Fluad, 99 received Agrippal. Blood samples were taken from all subjects in order to assess their antibody titre by the haemagglutination inhibition assay (HI), before (Time 0) and after (Time 1: 28 +/- 7 days) vaccination, against the A/H3N2 (A/Moscow/10/99), A/H1N1 (A/New Caledonia/20/99) and B/Shandong/7/97 antigens contained in the influenza vaccine in the 2002/2003 influenza season for the northern hemisphere. A good humoral antibody response was detected for both vaccines, meeting all the criteria of EMEA. The number of subjects in whom > or = 4-fold increase in antibody titre was recorded, in comparison with the pre-vaccination value, proved to be lower in the group vaccinated with AgrippaPl than in those vaccinated with the adjuvated preparation. Fluad" exhibited better immunogenicity than Agrippal. This difference was probably linked to the potentiated immune stimulation exerted by the adjuvant molecules. These results take on a particular importance if we consider that the immune system is weaker in the elderly; the administration of an adjuvated vaccine in such subjects is clearly preferable in that it provides greater and more prolonged protection. Both vaccines were generally well tolerated; no severe adverse events occurred in any of the subjects vaccinated, confirming the excellent safety profile of Fluad and Agrippal.

  4. Formulation, High Throughput In Vitro Screening and In Vivo Functional Characterization of Nanoemulsion-Based Intranasal Vaccine Adjuvants

    OpenAIRE

    Pamela T. Wong; Leroueil, Pascale R.; Smith, Douglas M.; Ciotti, Susan; Bielinska, Anna U.; Janczak, Katarzyna W.; Mullen, Catherine H.; Groom, Jeffrey V.; Taylor, Erin M; Passmore, Crystal; Makidon, Paul E.; O’Konek, Jessica J.; Myc, Andrzej; Hamouda, Tarek; Baker, James R.

    2015-01-01

    Vaccine adjuvants have been reported to induce both mucosal and systemic immunity when applied to mucosal surfaces and this dual response appears important for protection against certain pathogens. Despite the potential advantages, however, no mucosal adjuvants are currently approved for human use. Evaluating compounds as mucosal adjuvants is a slow and costly process due to the need for lengthy animal immunogenicity studies. We have constructed a library of 112 intranasal adjuvant candidate ...

  5. Oxidative state and oxidative metabolism in the brain of rats with adjuvant-induced arthritis.

    Science.gov (United States)

    Wendt, Mariana Marques Nogueira; de Sá-Nakanishi, Anacharis Babeto; de Castro Ghizoni, Cristiane Vizioli; Bersani Amado, Ciomar Aparecida; Peralta, Rosane Marina; Bracht, Adelar; Comar, Jurandir Fernando

    2015-06-01

    The purpose of the present study was to evaluate the oxidative status of the brain of arthritic rats, based mainly on the observation that arthritis induces a pronounced oxidative stress in the liver of arthritis rats and that morphological alterations have been reported to occur in patients with rheumatoid arthritis. Rats with adjuvant-induced arthritis were used. These animals presented higher levels of reactive oxygen species (ROS) in the total brain homogenate (25% higher) and in the mitochondria (+55%) when compared to healthy rats. The nitrite plus nitrate contents, nitric oxide (NO) markers, were also increased in both mitochondria (+27%) and cytosol (+14%). Arthritic rats also presented higher levels of protein carbonyl groups in the total homogenate (+43%), mitochondria (+69%) and cytosol (+145%). Arthritis caused a diminution of oxygen consumption in isolated brain mitochondria only when ascorbate was the electron donor. The disease diminished the mitochondrial cytochrome c oxidase activity by 55%, but increased the transmembrane potential by 16%. The pro-oxidant enzyme xanthine oxidase was 150%, 110% and 283% higher, respectively, in the brain homogenate, mitochondria and cytosol of arthritic animals. The same occurred with the calcium-independent NO-synthase activity that was higher in the brain homogenate (90%) and cytosol (122%) of arthritic rats. The catalase activity, on the other hand, was diminished by arthritis in all cellular fractions (between 30 and 40%). It is apparent that the brain of rats with adjuvant-induced arthritis presents a pronounced oxidative stress and a significant injury to lipids and proteins, a situation that possibly contributes to the brain symptoms of the arthritis disease.

  6. Randomized study of postoperative radiotherapy and simultaneous temozolomide without adjuvant chemotherapy for glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Kocher, M.; Mueller, R.P. [Dept. of Radiotherapy, Univ. Hospital, Cologne (Germany); Frommolt, P. [Inst. for Biostatistics, Informatics, and Epidemiology, Univ. Hospital, Cologne (Germany); Borberg, S.K. [Gemeinschaftspraxis for Radiation Oncology and Radiotherapy, Hannover (Germany); Ruehl, U. [Dept. of Radiotherapy, Vivantes Klinikum im Friedrichshain, Berlin (Germany); Steingraeber, M. [Dept. of Radiotherapy, Vivantes Klinikum Neukoelln, Berlin (Germany); Niewald, M. [Dept. of Radiotherapy, Univ. Hospital Homburg/Saar (Germany); Staar, S. [Dept. of Radiotherapy, Zentralkrankenhaus St.-Juergen-Str., Bremen (Germany); Stuschke, M. [Dept. of Radiotherapy, Univ. Hospital Essen (Germany); Becker, G. [Dept. of Radiotherapy, Klinik am Eichert, Goeppingen (Germany); Fischedick, A.R. [Dept. of Radiotherapy, Clemens-Hospital, Muenster (Germany); Herfarth, K. [Dept. of Radiotherapy, Univ. Hospital, Heidelberg (Germany); Grauthoff, H. [Dept. of Radiotherapy, Lukaskrankenhaus Neuss (Germany)

    2008-11-15

    Purpose: to evaluate the efficacy of simultaneous postoperative temozolomide radiochemotherapy in glioblastoma patients. Patients and methods: from February 2002 to July 2004, n = 65 patients from 11 German centers with macroscopic complete tumor resection were randomized to receive either postoperative radiotherapy alone (RT, n = 35) or postoperative radiotherapy with simultaneous temozolomide (RT + TMZ, n = 30). Patients were stratified according to age ({<=}/> 50 years) and WHO performance score (0-1 vs. 2). RT consisted of 60 Gy in 30 fractions. In the RT + TMZ arm, oral TMZ was administered daily at a dose of 75 mg/m{sup 2} including weekends (40-42 doses). Adjuvant treatment was not given, but in both arms, patients with recurrent tumors and in good condition (WHO 0-2) were scheduled for salvage chemotherapy with TMZ. Results: the trial was stopped early due to the results of EORTC-study 26981-22981 that showed a survival benefit for the combination of concomitant and adjuvant TMZ compared to radiotherapy alone. In total, 62/65 patients were evaluable. Stratification variables were well balanced ({<=} 50 years 26% vs. 20%, WHO 0-1 91% vs. 100%). Neither overall survival (median 17 vs. 15 months) nor progression-free survival (median 7 vs. 6 months) differed significantly between the two arms. In the RT (RT + TMZ) arm, 76% (62%) of the progressing patients received salvage chemotherapy with TMZ, 36% (50%) had a second resection. There was a time-constant trend for increased general quality of life (EORTC questionnaire QLQ C30) and brain-specific quality of life (EORTC questionnaire B20) in the combined arm. Lymphopenia G3-4 was more frequent (33 vs. 6%) in the RT + TMZ arm. Conclusion: after early closure of this trial, a benefit for progression-free survival for simultaneous TMZ radiochemotherapy alone could not be demonstrated. In both arms, salvage therapies were frequently used and probably had a major effect on overall survival. (orig.)

  7. Tumor regrowth between surgery and initiation of adjuvant therapy in patients with newly diagnosed glioblastoma

    Science.gov (United States)

    Pirzkall, Andrea; McGue, Colleen; Saraswathy, Suja; Cha, Soonmee; Liu, Raymond; Vandenberg, Scott; Lamborn, Kathleen R.; Berger, Mitchel S.; Chang, Susan M.; Nelson, Sarah J.

    2009-01-01

    To assess incidence and degree of regrowth in glioblastoma between surgery and radiation therapy (RT) and to correlate regrowth with presurgical imaging and survival, we examined images of 32 patients with newly diagnosed glioblastoma who underwent MR spectroscopic imaging (MRSI), perfusion-weighted imaging (PWI), and diffusion-weighted imaging (DWI) prior to surgery, after surgery, and prior to RT/temozolomide. Contrast enhancement (CE) in the pre-RT MR image was compared with postsurgical DWI to differentiate tumor growth from postsurgical infarct. MRSI and PWI parameters were analyzed prior to surgery and pre-RT. Postsurgical MRI indicated that 18 patients had gross total and 14 subtotal resections. Twenty-one patients showed reduced diffusion, and 25 patients showed new or increased CE. In eight patients (25%), the new CE was confined to areas of postsurgical reduced diffusion. In the other 17 patients (53%), new CE was found to be indicative of tumor growth or a combination of tumor growth and surgical injury. Higher perfusion and creatine within nonenhancing tumor in the presurgery MR were associated with subsequent tumor growth. High levels of choline and reduced diffusion in pre-RT CE suggested active metabolism and tumor cell proliferation. Median survival was 14.6 months in patients with interim tumor growth and 24 months in patients with no growth. Increased volume or new onset of CE between surgery and RT was attributed to tumor growth in 53% of patients and was associated with shorter survival. This suggests that reducing the time between surgery and adjuvant therapy may be important. The acquisition of metabolic and physiologic imaging data prior to adjuvant therapy may also be valuable in assessing regions of new CE and nonenhancing tumor. PMID:19229057

  8. Efficacy evaluation of two synthetic lysine lipidated tripeptides as vaccine adjuvants against HBsAg.

    Science.gov (United States)

    Sidiq, Tabasum; Khajuria, Anamika; Shafi, Syed; Ismail, Tabasum; Sampath Kumar, Halmathur; Kannappa Srinivas, Vellimedu; Krishna, Ella; Kamal Johri, Rakesh

    2013-04-01

    In the present investigation, adjuvant potential of two novel lipidated tripeptide lysine derivatives (KKSM and KKSMB) was evaluated using various in vitro and animal-derived models of humoral and cell-mediated immune events in response to hepatitis B surface antigen (HBsAg). The results were compared with alum adjuvanted with HBsAg. Both these molecules were found to stimulate anti-HBsAg IgG and neutralizing (IgG1 and IgG2a) antibody titres in mice sera. The two molecules stimulated the proliferation of T-lymphocyte sub-sets (CD4/CD8) as well as the production of soluble mediators of Th1 (IL-2 and IFN-γ) and Th2 response (IL-4) in spleen cell culture supernatant. Furthermore, the two lipidated tripeptides enhanced the CD4, CD8, CD3 and CD19 cell populations as well as CD4/CD8 derived IL-2, IL-4, IFN-γ and TNF-α in whole blood of treated mice. There was found to be the significant enhancement in the release of IL-12, IFN-γ and nitrite content in macrophage supernatant. Moreover, the two lipidated tripeptides enhanced the population of CD80 and CD86 in spleen-derived macrophages and did not show any hemolytic effect on rabbit RBCs. Taken together, these results suggest that both these molecules are the potent enhancers of anti-HBsAg immune response via augmenting Th1/Th2 response in a dose dependent manner. PMID:23474022

  9. Role of adjuvant postoperative external beam radiotherapy for well differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jeanny; Wu, Hong Gyun; Youn, Yeo Kyu; Lee, Kyu Eun; Kim, Kwang Hyun; Park, Do Joon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2013-09-15

    To analyze the outcome of adjuvant postoperative external beam radiotherapy (EBRT) in well-differentiated thyroid cancer (WDTC). We identified 84 patients treated with EBRT for WDTC from February 1981 to December 2010. Among them, we analyzed 39 patients who received EBRT after initial radical surgery. Twenty-four females and 15 males were included. The median age was 49 years (range, 16 to 72 years). There were 34 papillary thyroid carcinomas and 5 follicular thyroid carcinomas. Most patients showed pathologic T3/T4 stage (54%/26%). Ten patients (25.6%) had gross residual tumors. Five patients (12.8%) had tumor cells at the margin. The median EBRT dose and fraction size were 62.6 Gy and 1.8 to 2.0 Gy, respectively. The median follow-up was 73 months (range, 21 to 372 months). The five-year overall survival (OS) and locoregional recurrence free survival (LRFS) were 97.4% and 86.9%, respectively. Locoregional failures occurred in 5 and all failure sites were the neck node area. In univariate analysis, OS was significantly influenced by invasion of the trachea (p = 0.016) or esophagus (p = 0.006). LRFS was significantly decreased by male (p = 0.020), gross residuum after resection (p = 0.002), close or positive tumor at surgical margin involvement (p = 0.044), and tracheal invasion (p = 0.040). No significant prognostic factor was identified in the multivariate analysis. No patient experienced the Radiation Therapy Oncology Group grade 3 or more toxicity. Our locoregional control rate of 87.2% is comparable to historical controls with surgery alone, even though our study had a large proportion of advanced stage. Adjuvant EBRT may an effective and safe treatment option in patients with WDTC.

  10. EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas

    Science.gov (United States)

    Zhang, Yi; Tolani, Bhairavi; Mo, Minli; Zhang, Hua; Zheng, Qingfeng; Yang, Yue; Cheng, Runfen; Jin, Joy Q.; Luh, Thomas W.; Yang, Cathryn; Tseng, Hsin-Hui K.; Giroux-Leprieur, Etienne; Woodard, Gavitt A.; Hao, Xishan; Wang, Changli; Jablons, David M.; He, Biao

    2015-01-01

    Background Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer (NSCLC). Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC. Methods Two independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro. Results EMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration. Conclusions EMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT). EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. PMID:26132438

  11. EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas.

    Directory of Open Access Journals (Sweden)

    Dongsheng Yue

    Full Text Available Squamous cell carcinomas (SCC account for approximately 30% of non-small cell lung cancer (NSCLC. Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC.Two independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro.EMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration.EMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT. EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy.

  12. Adjuvant chemoradiotherapy for adenocarcinoma of the stomach. A new progress?; Chimioradiotherapie dans le traitement adjuvant des adenocarcinomes gastriques: reelle avancee?

    Energy Technology Data Exchange (ETDEWEB)

    Mineur, L. [Institut Sainte Catherine, 84 - Avignon (France); Lacaine, F. [Hopital Tenon, 75 - Paris (France); Ychou, M. [Centre Regional de Lutte Contre le Cancer Val d' Aurelle, Service d' Oncologie, 34 - Montpellier (France); Bosset, J.F. [Centre Hospitalier Universitaire, Service de Radiotherapie, 25 - Besancon (France); Daban, A. [Centre Hospitalier Universitaire, Service de Radiotherapie, 86 - Poitiers (France)

    2002-11-01

    Frequency of local and distant failures after gastrectomy has led to extended lymph nodes dissection to obtain a better locoregional control. However, five year survival rates were not significantly different between patients undergoing D2 and D1 lymphadenectomy, and higher morbidity and post operative deaths were reported in large randomized trials (respectively 25% vs 48% and 4 vs 13%). Additionally, several met-analysis failed to demonstrate a significant survival advantage with adjuvant chemotherapy. The results of the first trial demonstrating one advantage to adjuvant post-operative chemoradiotherapy should modify the standard care. Disease free and overall survival after surgery alone and after surgery and concurrent chemoradiotherapy were respectively 31% vs 48% and 41% vs 50%. The inter-group trial demonstrate that better local control improve survival if radiation fields include stamps, tumour bed, proximal nodal chains and nodes corresponding to D2 extended lymph nodes dissection. Treatment was feasible with few severe toxic effects (1%). Of the 281 patients, 17% stopped treatment because toxic effects. Technical modalities of radiotherapy and post-operative nutrition support which are critical points of interest for this treatment, are also discussed. (authors)

  13. A STUDY ON ADJUVANT HEAD CORING IN PATIENTS UNDERGOING LONGITUDINAL PANCREATICOJEJUNOSTOMY AND ITS AID IN PAIN REDUCTION IN CHRONIC PANCREATITIS

    Directory of Open Access Journals (Sweden)

    Sudhansu Sekhar Mohanty

    2016-07-01

    Full Text Available BACKGROUND The condition manifests as recurrent intractable abdominal pain. 1 This is the most important indication for surgical procedures. The pain is caused by increased pancreatic parenchymal and ductal pressure. Another cause is that chronic inflammation of the pancreas may lead to fibrosis of the peripancreatic capsule and perilobular parenchyma, which impairs local and regional blood flow, therefore causing pain through tissue ischaemia and acidosis. 2 This is the rationalisation behind adding the head coring to the decompression surgeries that had been classically in practice. METHODS This is a retrospective study. The study period spans over from January 2003 to December 2013, which is a 10-year period. Patients with intractable and non-relenting abdominal pain and a diagnosis of chronic pancreatitis with evidence of fibrosis of head of pancreas in imaging studies were included. 35 patients were randomly allocated for Head coring and LPJ by lottery method. The patients were analysed for duration of surgery, hospital stay, operative/postoperative complications and assessment of postoperative pain relief. Pain relief was assessed as complete (No analgesic required, satisfactory (Tolerable pain with normal daily activities and unsatisfactory (Hospitalisation and hampered daily activities. RESULTS Alcohol consumption (65.71% was the main cause of pancreatitis in the study group, followed by gallstones (14.28% and idiopathic (20% cause. Head coring (120 minutes takes a median operative time of 30 minutes more when done adjuvant to LPJ (90 minutes. Incidence of complications were comparable in both the surgeries. The common complications of prolonged ileus and wound infection are in the percentage of 12.5% in only LPJ and 15.78% in adjuvant head coring surgeries. Pain relief was good when the complete and satisfactory groups were compared. But there is not much of difference in unsatisfactory group comparison. CONCLUSION A 30 minutes

  14. Green synthesis and evaluation of silver nanoparticles as adjuvant in rabies veterinary vaccine

    Science.gov (United States)

    Asgary, Vahid; Shoari, Alireza; Baghbani-Arani, Fahimeh; Sadat Shandiz, Seyed Ataollah; Khosravy, Mohammad Sadeq; Janani, Alireza; Bigdeli, Razieh; Bashar, Rouzbeh; Cohan, Reza Ahangari

    2016-01-01

    Background Green synthesis of nanoparticles by plant extracts plays a significant role in different applications. Recently, several studies were conducted on the use of nanoparticles as adjuvant. The main aim of this study was to evaluate green synthesized silver nanoparticles (AgNPs) as adjuvant in rabies veterinary vaccine and compare the results with the existing commercially available alum adjuvant. Materials and methods In the current study, AgNPs were prepared by the reduction of aqueous silver nitrate by leaf extract of Eucalyptus procera. The formation of AgNPs was confirmed by ultraviolet (UV)–visible spectrophotometer, scanning electron microscopy, dynamic light scattering, and X-ray diffraction analysis. Then, different amounts of AgNPs (200 µg, 400 µg, 600 µg, and 800 µg) were added to 1 mL of inactivated rabies virus. The loaded vaccines (0.5 mL) were injected intraperitoneally into six Naval Medical Research Institute mice in each group on days 1 and 7. On the 15th day, the mice were intracerebrally challenged with 0.03 mL of challenge rabies virus (challenge virus strain-11, 20 lethal dose [20 LD50]), and after the latency period of rabies disease in mice (5 days), the mice were monitored for 21 days. Neutralizing antibodies against rabies virus were also investigated using the rapid fluorescent focus inhibition test method. The National Institutes of Health test was performed to determine the potency of optimum concentration of AgNPs as adjuvant. In vitro toxicity of AgNPs was assessed in L929 cell line using MTT assay. In addition, in vivo toxicity of AgNPs and AgNPs-loaded vaccine was investigated according to the European Pharmacopeia 8.0. Results AgNPs were successfully synthesized, and the identity was confirmed by UV–visible spectrophotometry and X-ray diffraction analysis. The prepared AgNPs were spherical in shape, with an average size of 60 nm and a negative zeta potential of −14 mV as determined by dynamic light scattering

  15. Adjuvant radiotherapy for uterine papillary serous carcinoma: Whole abdominopelvic or pelvic irradiation?

    International Nuclear Information System (INIS)

    disease progression. Five year disease specific survival for IIIA and below was 72% vs. 25% for stages IIIB and above. 2.) There were a total of 5 local/regional disease failures in the XRT treatment portals for the entire group. The rate of local-regional control for the entire group in the RT treatment portal was 72%. One patient received WAI for a stage IB disease and failed in the abdomen. Two patients who received pelvic irradiation for stage IIIB disease and two others treated with WAI also for stage IIIB disease failed in the treatment portals. The rate of local/regional control for stages IIIA and below was 86% vs. 42% for stages IIIB and above. Conclusions: 1.) Our data confirm the aggressive natural history of UPSC in that more than half of the patients died within five years. 2.) In spite of the rarity of this histology, our experience revealed that surgically staged patients with stages IIIA and below can achieve reasonable survival and local/regional disease control with adjuvant irradiation. 3.) For stages IIIA and below, pelvic XRT is as effective as WAI. 4.) For patients with stages IIIB and above the survival was poor due to distant disease progression. Even though more patients in this group received WAI, there was a higher rate of abdominal/pelvic failure when compared with earlier stage disease treated mostly with pelvic RT field

  16. Response and Long-Term Effect of Patients with Triple-Negative Breast Cancer Receiving Neo-Adjuvant Anthracycline-Based

    Institute of Scientific and Technical Information of China (English)

    Zhengkui Sun; Xingtian Ma; Yudong Wu; Fan Fan; Xianghua Wan; Airong Fu

    2009-01-01

    OBJECTIVE The breast cancer lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) is defined as the Triple-negative breast cancer (TNBC). Our purpose is to compare the response and long-term effect of the TNBC and non-TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy, and to investigate the mechanisms of TNBC affecting the survivals. METHODS Data of long-term follow-up (median, 5.4 years) of 326 patients who received neo-adjuvant chemotherapy with anthracycline-based regimen, during a period from 2000 to 2003, were analyzed. Expressions of ER, PR, HER-2, P53, Ki-67 and E-cadherin were determined using immunohistochemical staining method. A multivariate Cox regression analysis was used to analyze independent prognostic factors affecting the relapse-free survival (RFS) and overall survival (OS) rates. Clinical effects of the neo-adjuvant anthracycline-based chemotherapeutic regimen and the RFS and OS rates were compared between the patients with TNBC and non-TNBC, and the correlations among the triple- negative phenotype (TNP), tumor grading and the expressions of P53, Ki-67 and E-cadherins were analyzed. RESULTS TNP, TNM staging, histological grades, clinical response of the neo-adjuvant chemotherapy and pathological complete remission (pCR) rate were the independent prognostic factors affecting the survival rates. Furthermore, 70 (21.5%) of the 326 patients suffered TNBC. Compared with the subjects in non- TNBC group, the patients with TNBC had a significantly higher pCR rate (P=0.046) and clinical response rate (P=0.037), but also decreased 5-year RFS (P=0.001) and OS (P=0.004) rates. The RFS and OS rates were not improved in the TNBC patients who achieved a clinical remission after the neo-adjuvant chemotherapy. The triple-negative phenotype was positively correlated with the level of P53, Ki-67 expression (P=0.007, P=0.028), but negatively correlated with level of

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

    Science.gov (United States)

    Bechmann, Troels; Olsen, Dorte Aalund; Jakobsen, Erik Hugger; Madsen, Jonna Skov; Brandslund, Ivan; Jylling, Anne Marie Bak; Steffensen, Karina Dahl; Jakobsen, Anders

    2013-04-01

    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) and fluorescence in situ hybridization (FISH). In this study, we assessed the clinical significance of tissue HER2 status determined by a quantitative immunoassay using ADVIA Centaur. We investigated the hypothesis that the clinical outcome is worse in a group of patients defined as tissue HER2-positive only 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 for invasive disease-free survival (IDFS) and 4.2 years for overall survival (OS). The quantitative Centaur assay defined a greater number of patients (100 patients, 26.4%) as HER2-positive than IHC/FISH (63 patients, 16.6%) (P<0.0001). No significant difference in IDFS (P=0.159) and OS (P=0.150) was observed among the four groups of patients. However, in the IHC/FISH-positive group without adjuvant HER2-targeted therapy (group 2), a significantly greater number of events was found compared to the Centaur-positive group without adjuvant HER2-targeted therapy (group 3) for both IDFS (P=0.025) and OS (P=0.020). Quantitative HER2 determination by Centaur did not define a new group of patients eligible for HER2-targeted therapy. Currently, tissue HER2 status defined

  18. STRUCTURE AND IMMUNE ADJUVANT PROPERTIES OF CPG-D

    Directory of Open Access Journals (Sweden)

    V. S. Polovinkina

    2010-01-01

    Full Text Available Bacterial DNA, along with other bacterial pathogen-associated molecular structures, may activate both innate and adaptive immune systems. This activity is associated with by nonmethylated CpG dinucleotides, which are present in the bDNA molecule, and it may be simulated by synthetic CpG oligodeoxynucleotides (ODNs. Non-methylated CpG motifs are recognized by Toll-like receptor 9 that triggers the induction of cell signaling pathways, activating proinflammatory cytokine synthesis by immune competent cells, and triggering the immune protection mechanisms. In present review we consider structure, functions, adjuvant features, immune properties and potential clinical applications of bacterial DNA and various classes of synthetic non-methylated CpG-ODNs.

  19. Uncaria tomentosa—Adjuvant Treatment for Breast Cancer: Clinical Trial

    Directory of Open Access Journals (Sweden)

    Maria do Carmo Santos Araújo

    2012-01-01

    Full Text Available Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide, were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.

  20. Adjuvant systemic therapy in older women with breast cancer.

    Science.gov (United States)

    Leone, Julieta; Leone, Bernardo Amadeo; Leone, José Pablo

    2016-01-01

    Breast cancer in the elderly is an increasing clinical problem. In addition, ~60% of deaths from breast cancer occur in women aged 65 years and older. Despite this, older women with breast cancer have been underrepresented in clinical trials, and this has led to less than optimal evidence to guide their therapy. The management of elderly women with early breast cancer is a complex process that requires careful evaluation of life expectancy, comorbidities, patient values, and risks and benefits of available treatment options. This review will focus on current adjuvant systemic therapy options for older women with breast cancer, discuss the principles in the decision-making process, and define the role of endocrine therapy, chemotherapy, and targeted agents. PMID:27524919

  1. Uncaria tomentosa-Adjuvant Treatment for Breast Cancer: Clinical Trial.

    Science.gov (United States)

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma-Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.

  2. Uncaria tomentosa—Adjuvant Treatment for Breast Cancer: Clinical Trial

    Science.gov (United States)

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L.; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer. PMID:22811748

  3. Adjuvant systemic therapy in older women with breast cancer

    Science.gov (United States)

    Leone, Julieta; Leone, Bernardo Amadeo; Leone, José Pablo

    2016-01-01

    Breast cancer in the elderly is an increasing clinical problem. In addition, ~60% of deaths from breast cancer occur in women aged 65 years and older. Despite this, older women with breast cancer have been underrepresented in clinical trials, and this has led to less than optimal evidence to guide their therapy. The management of elderly women with early breast cancer is a complex process that requires careful evaluation of life expectancy, comorbidities, patient values, and risks and benefits of available treatment options. This review will focus on current adjuvant systemic therapy options for older women with breast cancer, discuss the principles in the decision-making process, and define the role of endocrine therapy, chemotherapy, and targeted agents. PMID:27524919

  4. BRCA1/2 mutation testing in breast cancer patients: a prospective study of the long-term psychological impact of approach during adjuvant radiotherapy

    OpenAIRE

    Schlich-Bakker, K.J.; Ausems, M.G.E.M.; Kroode, H.F.J. ten; Wárlám-Rodenhuis, C.C.; Bout, J. van den

    2007-01-01

    This study assessed psychological distress during the first year after diagnosis in breast cancer patients approached for genetic counseling at the start of adjuvant radiotherapy and identified those vulnerable to long-term high distress. Of the approached patients some chose to receive a DNA test result (n = 58), some were approached but did not fulfill criteria for referral (n = 118) and some declined counseling and/or testing (n = 44). The comparative group consisted of patients not eligib...

  5. Randomized Trial: Immunogenicity and Safety of Coadministered Human Papillomavirus-16/18 AS04-Adjuvanted Vaccine and Combined Hepatitis A and B Vaccine in Girls

    DEFF Research Database (Denmark)

    Pedersen, Court; Breindahl, Morten; Aggarwal, Naresh;

    2012-01-01

    This randomized, open, controlled, multicenter study (110886/NCT00578227) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (HPV-16/18 vaccine) coadministered with inactivated hepatitis A and B (HAB) vaccine. Coprimary objectives were to demonstrate noninferiority of hepatitis A......, hepatitis B, and HPV-16/18 immune responses at month 7 when vaccines were coadministered, compared with the same vaccines administered alone....

  6. Biopersistence and brain translocation of aluminum adjuvants of vaccines

    Directory of Open Access Journals (Sweden)

    Romain Kroum Gherardi

    2015-02-01

    Full Text Available Aluminum oxyhydroxide (alum is a crystaline compound widely used as an immunologic adjuvant of vaccines. Concerns linked to the use of alum particles emerged following recognition of their causative role in the so-called macrophagic myofasciitis (MMF lesion detected in patients with myalgic encephalomyelitis/chronic fatigue/syndrome. MMF revealed an unexpectedly long-lasting biopersistence of alum within immune cells in presumably susceptible individuals, stressing the previous fundamental misconception of its biodisposition. We previously showed that poorly biodegradable aluminum-coated particles injected into muscle are promptly phagocytozed in muscle and the draining lymph nodes, and can disseminate within phagocytic cells throughout the body and slowly accumulate in brain. This strongly suggests that long-term adjuvant biopersistence within phagocytic cells is a prerequisite for slow brain translocation and delayed neurotoxicity. The understanding of basic mechanisms of particle biopersistence and brain translocation represents a major health challenge, since it could help to define susceptibility factors to develop chronic neurotoxic damage. Biopersistence of alum may be linked to its lysosome-destabilizing effect, which is likely due to direct crystal-induced rupture of phagolysosomal membranes. Macrophages that continuously perceive foreign particles in their cytosol will likely reiterate, with variable interindividual efficiency, a dedicated form of autophagy (xenophagy until they dispose of alien materials. Successful compartmentalization of particles within double membrane autophagosomes and subsequent fusion with repaired and re-acidified lysosomes will expose alum to lysosomal acidic pH, the sole factor that can solubilize alum particles. Brain translocation of alum particles is linked to a Trojan horse mechanism previously described for infectious particles (HIV, HCV, that obeys to CCL2 signaling the major inflammatory monocyte

  7. The relevance of adjuvant therapy in primary carcinoma of the Fallopian tube, Stages I and II: Irradiation vs. chemotherapy

    International Nuclear Information System (INIS)

    Introduction: Primary carcinoma of the Fallopian tube (FTC) is a rare but extremely aggressive neoplasm. It must be expected to cause up to 40% of tumor-related deaths even in Stage I, and up to 57% in Stage II. Due to its rarity, there exist only a few and divergent reports on the value of adjuvant therapy. Therefore the present study aims at evaluating the influence of postoperative adjuvant therapy on FTC by studying the effects of irradiation and chemotherapy on the overall survival of patients in Stages I and II. Patients and Methods: We investigated 95 cases of FTC in Stages I (n = 66) and II (n = 29) in a retrospective multicenter study. Group I (n = 32) are patients who underwent a complete irradiation with cobalt or photon energies of 23 MV (administering a daily dose of 2 Gy resulted in a total of 45-52 Gy in the pelvic areas). Group II (n = 31) consists of those cases who received postoperative chemotherapy with platinum. Thirty-two women were excluded from this study because they had other chemotherapies, incomplete irradiation, or no adjuvant therapy at all. Results: Median survival time was 57 months in Group I patients (95% confidence interval 33-81 months), compared to 73 months (95% confidence interval, 68-78 months) in the chemotherapeutically treated Group II. This difference did not prove to be statistically significant (p = 0.476). If primary surgical therapy is included in the evaluation, and patients with total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) are compared to those with additional radical lymphadencetomy (TAH+BSO+lymph nodes), the latter group's overall survival essentially improves but fails to reach statistical significance. Their 5-year survival rate is 83% against 58% in the TAH+BSO group (p 0.12). Conclusion: Chemotherapy and irradiation are two adjuvant therapies that are similarly effective in FTC of Stages I and II, with chemotherapy being preferred at the present time. Primary surgical treatment

  8. Effect of Cornus officinalis glycoside on adjuvant-induced arthritis in rats

    Institute of Scientific and Technical Information of China (English)

    SHI PING ZHAO; JIAN MIN LI; GUI XIANG FU; YONG ZHOU

    2006-01-01

    The aim of this study was to explore the effect of Cornus officinalis glucosides (COG) on adjuvant-induced arthritis in rats and its mechanism. Seventy-two rats were divided into six groups of normal, model, Dexasone (0. 125 mg/kg), high-dose COG (240 mg/kg), mid-dose COG (120 mg/kg),and low-dose COG (60 mg/kg). Rat arthritis was induced by injection of Freund's complete adjuvant in the hind paws. All treatment started from the day the arthritis was induced. The edema degree of the adjuvant injection location was determined on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 20, 23 and the opposite side was observed on days 11, 13, 15, 17, 20, 23 after the injection of adjuvant. All rats were sacrificed on day 24 after the injection of adjuvant for microscopic examination of the ankle, and for the study of the immunological molecular mechanism. The results showed that the COG significantly suppressed both the primary and secondary edema, improved pathological injuries of adjuvant arthritis (AA)rat ankles, significantly suppressed the proliferation of T lymphocytes and DTH reaction. It significantly suppressed IL-1, IL-6 and TNF-α production from peritoneal macrophages and PGE2 in plasma. In conclusion, the Cornus officinalis glucosides (COG) is able to prevent and cure the rat adjuvant-induced arthritis, and can suppress the production of pro-inflammatory cytokine IL-1, IL-6, TNF-α and PGE2.

  9. Immune Adjuvant Effect of Molecularly-defined Toll-Like Receptor Ligands

    Directory of Open Access Journals (Sweden)

    Deana N. Toussi

    2014-04-01

    Full Text Available Vaccine efficacy is optimized by addition of immune adjuvants. However, although adjuvants have been used for over a century, to date, only few adjuvants are approved for human use, mostly aimed at improving vaccine efficacy and antigen-specific protective antibody production. The mechanism of action of immune adjuvants is diverse, depending on their chemical and molecular nature, ranging from non-specific effects (i.e., antigen depot at the immunization site to specific activation of immune cells leading to improved host innate and adaptive responses. Although the detailed molecular mechanism of action of many adjuvants is still elusive, the discovery of Toll-like receptors (TLRs has provided new critical information on immunostimulatory effect of numerous bacterial components that engage TLRs. These ligands have been shown to improve both the quality and the quantity of host adaptive immune responses when used in vaccine formulations targeted to infectious diseases and cancer that require both humoral and cell-mediated immunity. The potential of such TLR adjuvants in improving the design and the outcomes of several vaccines is continuously evolving, as new agonists are discovered and tested in experimental and clinical models of vaccination. In this review, a summary of the recent progress in development of TLR adjuvants is presented.

  10. [PROGNOSTIC SIGNIFICANCE OF ADJUVANT RADIOTHERAPY IN EARLY IB1 STAGE CERVICAL CANCER].

    Science.gov (United States)

    Ismail, E; Kornovski, Y

    2015-01-01

    The cervical cancer is one of the most common malignancies. Worldwide 500,000 women a year become ill from cervical cancer. The aim of the study was to establish the role of adjuvant radiotherapy in patients with IB1 cervical cancer in terms of disease free survival. Between 2002-2012, 132 patients diagnosed as IB1 stage according to FIGO criteria were enrolled in the study. Depending on the administered therapy the patients were divided into two groups--Group 1-93 patients were treated surgically and with adjuvant radiotherapy and Group 2--39 patients were treated surgically without adjuvant radiotherapy Surgery was radical hysterectomy class III and pelvic or paraaortic lymph node dissection(in cases of bulky paraaortic nodes), and adjuvant RT-telegamma therapy(TGT) in dose 52 Gy. The frequency of recurrence in a Group I (surgery and TGT) is 9.7%. Tree and five years disease free survival (DFS) is 88%. The frequency of recurrence in a Group 2 (surgery without TGT) is 25.6%. Tree and five years DFS respectively are 70% and 65%. In an analysis of oncological results establish that adjuvant TGT after surgery significantly increases DFS. On the other hand the addition of adjuvant TGT increases the patients morbidity Therefore should determine which are the risk factors for the occurrence of relapses and select group of patients who would benefit from adjuvant TGT and the risk of complications in them would be justified. PMID:26817258

  11. Oral Zinc Sulfate as Adjuvant Treatment in Children With Nephrolithiasis: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Parsa Yousefichaijan

    2015-12-01

    Full Text Available Background: Nephrolithiasis in children is associated with a high rate of complications and recurrence. Objectives: Since some evidences reported that zinc has an important place amongst inhibitors of crystallization and crystal growth, we decided to assess the effectiveness of oral zinc sulfate as adjuvant treatment in children with nephrolithiasis. Patients and Methods: This was a randomized, double-blind, placebo-controlled clinical trial. 102 children in the age range 1 month to 11 years with first nephrolithiasis were recruited. Patients were randomly divided into two equal groups (intervention and control groups. Intervention group received conservative measures for stones and 1 mg/kg/day (maximum 20 mg/day oral zinc sulfate syrup for 3 months. Control group received placebo in addition to conservative measures, also for 3 months. Patients were followed up by ultrasonography for 9 months, in 5 steps (at the end of 1st, 2nd, 3rd, 6th and 9th month after treatment assessing size and number of stones in the kidneys. Results: Only at the end of the first month, the average number (intervention: 1.15 ± 3.78, control: 1.3 ± 2.84 (P = 0.001 and size (cm (intervention: 0.51 ± 1.76, control: 0.62 ± 1.39 (P = 0.001 of stones was significantly lower in the intervention group, and in other points there was no significant therapeutic efficacy in oral zinc adjuvant treatment compared to conservative treatment alone. Also, during the 9-month follow-up, the number and size of stones in both groups decreased significantly (both: P < 0.0001 in a way that the decrease in the intervention group showed no difference with the control group. Conclusions: Adjuvant treatment with zinc is not more effective than consecutive treatment in children with nephrolithiasis. However, further studies are recommended due to the lack of clinical evidence in this field.

  12. Trypanosoma cruzi adjuvants potentiate T cell-mediated immunity induced by a NY-ESO-1 based antitumor vaccine.

    Directory of Open Access Journals (Sweden)

    Caroline Junqueira

    Full Text Available Immunological adjuvants that induce T cell-mediate immunity (TCMI with the least side effects are needed for the development of human vaccines. Glycoinositolphospholipids (GIPL and CpGs oligodeoxynucleotides (CpG ODNs derived from the protozoa parasite Trypanosoma cruzi induce potent pro-inflammatory reaction through activation of Toll-Like Receptor (TLR4 and TLR9, respectively. Here, using mouse models, we tested the T. cruzi derived TLR agonists as immunological adjuvants in an antitumor vaccine. For comparison, we used well-established TLR agonists, such as the bacterial derived monophosphoryl lipid A (MPL, lipopeptide (Pam3Cys, and CpG ODN. All tested TLR agonists were comparable to induce antibody responses, whereas significant differences were noticed in their ability to elicit CD4(+ T and CD8(+ T cell responses. In particular, both GIPLs (GTH, and GY and CpG ODNs (B344, B297 and B128 derived from T. cruzi elicited interferon-gamma (IFN-γ production by CD4(+ T cells. On the other hand, the parasite derived CpG ODNs, but not GIPLs, elicited a potent IFN-γ response by CD8(+ T lymphocytes. The side effects were also evaluated by local pain (hypernociception. The intensity of hypernociception induced by vaccination was alleviated by administration of an analgesic drug without affecting protective immunity. Finally, the level of protective immunity against the NY-ESO-1 expressing melanoma was associated with the magnitude of both CD4(+ T and CD8(+ T cell responses elicited by a specific immunological adjuvant.

  13. Is adjuvant radiotherapy warranted in resected pT1-2 node-positive rectal cancer?

    International Nuclear Information System (INIS)

    Stage T1-2 rectal cancers are unlikely to have lymph node metastases and neoadjuvant therapy is not routinely administered. Postoperative management is controversial if lymph node metastases are detected in the resected specimen. We studied the outcomes of patients with pT1-2 node-positive rectal cancer in order to determine whether adjuvant radiotherapy was beneficial. We conducted a retrospective analysis of 284 patients with pathological T1-2 node-positive rectal cancer from a single institution. Outcomes, including local recurrence (LR), distant metastasis (DM), disease free survival (DFS) and overall survival (OS), were studied in patients with detailed TN staging and different adjuvant treatment modalities. The overall 5-year LR, DM, DFS and OS rates for all patients were 12.5%, 32.9%, 36.4% and 76.8%, respectively. Local control was inferior among patients who received no adjuvant therapy. Patients could be divided into three risk subsets: Low-risk, T1N1; Intermediate-risk, T2N1 and T1N2; and High-risk, T2N2. The 5-year LR rates were 5.3%, 9.8% and 26.4%, respectively (p = 0.005). In High-risk patients, addition of radiotherapy achieved a 5-year LR rate of 9.1%, compared 34.8% without radiotherapy. In our study, we provide the detailed outcomes and preliminary survival analysis in a relatively infrequent subset of rectal cancer. Three risk subsets could be identified based on local control for pT1-2 node positive rectal cancer. Postoperative treatment needs to be individualized for patients with pT1-2 node-positive rectal cancer

  14. Protective immune response against Toxoplasma gondii elicited by a recombinant DNA vaccine with a novel genetic adjuvant.

    Science.gov (United States)

    Zhou, Huaiyu; Min, Juan; Zhao, Qunli; Gu, Qinmin; Cong, Hua; Li, Ying; He, Shenyi

    2012-02-27

    Previous immunological studies from our laboratory have demonstrated the potential role of Toxoplasma gondii antigens SAG1 and GRA2 as vaccine candidates. To further evaluate the vaccine's effects, a series of recombinant DNA vaccines pVAX1-SAG1, pVAX1-GRA2 and pVAX1-SAG1-GRA2, termed pSAG1, pGRA2 and pSAG1-GRA2, respectively, were constructed. A plasmid pVAX1-S/PreS2, termed pSPreS2 encoding hepatitis B virus (HBV) surface antigen (HBsAg) S and PreS2 as a novel genetic adjuvant, was also constructed. The expression abilities of those DNA plasmids were examined in HFF cells by Western blotting. Then BALB/c mice were intramuscularly immunized with DNA plasmids and followed by challenging with the highly virulent T. gondii RH strain. The results demonstrated that the recombinant DNA vaccine pSAG1-GRA2 was capable of eliciting high levels of antibodies, a Th1 type of immune response with significant production of IFN-γ and low levels of IL-4 or IL-10 in BALB/c mice, and partial protection against the acute phase of toxoplasmosis as compared to pSAG1, pGRA2 and controls. In addition, the adjuvant pSPreS2 formulated with DNA vaccine induced a Th1 type of immune response and therefore might be a novel genetic adjuvant to DNA vaccine for further investigation. PMID:22240340

  15. Trypanosoma cruzi adjuvants potentiate T cell-mediated immunity induced by a NY-ESO-1 based antitumor vaccine.

    Science.gov (United States)

    Junqueira, Caroline; Guerrero, Ana Tereza; Galvão-Filho, Bruno; Andrade, Warrison A; Salgado, Ana Paula C; Cunha, Thiago M; Ropert, Catherine; Campos, Marco Antônio; Penido, Marcus L O; Mendonça-Previato, Lúcia; Previato, José Oswaldo; Ritter, Gerd; Cunha, Fernando Q; Gazzinelli, Ricardo T

    2012-01-01

    Immunological adjuvants that induce T cell-mediate immunity (TCMI) with the least side effects are needed for the development of human vaccines. Glycoinositolphospholipids (GIPL) and CpGs oligodeoxynucleotides (CpG ODNs) derived from the protozoa parasite Trypanosoma cruzi induce potent pro-inflammatory reaction through activation of Toll-Like Receptor (TLR)4 and TLR9, respectively. Here, using mouse models, we tested the T. cruzi derived TLR agonists as immunological adjuvants in an antitumor vaccine. For comparison, we used well-established TLR agonists, such as the bacterial derived monophosphoryl lipid A (MPL), lipopeptide (Pam3Cys), and CpG ODN. All tested TLR agonists were comparable to induce antibody responses, whereas significant differences were noticed in their ability to elicit CD4(+) T and CD8(+) T cell responses. In particular, both GIPLs (GTH, and GY) and CpG ODNs (B344, B297 and B128) derived from T. cruzi elicited interferon-gamma (IFN-γ) production by CD4(+) T cells. On the other hand, the parasite derived CpG ODNs, but not GIPLs, elicited a potent IFN-γ response by CD8(+) T lymphocytes. The side effects were also evaluated by local pain (hypernociception). The intensity of hypernociception induced by vaccination was alleviated by administration of an analgesic drug without affecting protective immunity. Finally, the level of protective immunity against the NY-ESO-1 expressing melanoma was associated with the magnitude of both CD4(+) T and CD8(+) T cell responses elicited by a specific immunological adjuvant.

  16. Enhanced humoral response to influenza vaccine in aged mice with a novel adjuvant, rOv-ASP-1.

    Science.gov (United States)

    Jiang, Jiu; Fisher, Erin M; Concannon, Mark; Lustigman, Sara; Shen, Hao; Murasko, Donna M

    2016-02-10

    Immunization is the best way to prevent seasonal epidemics and pandemics of influenza. There are two kinds of influenza vaccines available in the United States: an inactivated vaccine (TIV) and an attenuated vaccine; however, only TIV is approved for immunization of the elderly population. While the aged population has the highest rate of influenza vaccination, the protective efficacy is low as evidenced by elderly individuals having the highest mortality associated with influenza. Recently, we reported that an adjuvant derived from the helminth parasite Onchocerca volvulus, named O. volvulus activation-associated secreted protein-1 (Ov-ASP-1), can significantly enhance the protective efficacy of an inactivated vaccine (TIV) in young adult mice. In the current study, we examined whether this recombinant Ov-ASP-1 (rOv-ASP-1) can enhance the efficacy of TIV in aged mice as well. While primary immunization with TIV alone produced only a low level of influenza-specific antibodies (total IgG, IgG1, and IgG2c) in aged mice, the antibody levels were significantly increased after immunization with TIV+rOv-ASP-1. More importantly, the level of the total IgG in aged mice administered TIV+rOv-ASP-1 was comparable to that of young adult mice immunized with TIV alone. Co-administration of rOv-ASP-1 induced a low level of cross-reactive antibody and enhanced the protective efficacy of TIV in aged mice, reflected by significantly increased survival after challenge with a heterologous influenza virus. rOv-ASP-1 was also superior to the conventional adjuvant alum in inducing specific IgG after TIV immunization in aged mice, and in conferring protection after challenge. These results demonstrate that rOv-ASP-1 may serve as a potential adjuvant for influenza vaccine to improve the efficacy of protection in the elderly. PMID:26795365

  17. Tissue-specific regulation of expression and activity of P-glycoprotein in adjuvant arthritis rats.

    Science.gov (United States)

    Achira, Meguru; Totsuka, Ryuichi; Fujimura, Hisako; Kume, Toshiyuki

    2002-07-01

    Cyclosporine A and steroids are effective against rheumatoid arthritis and also known as substrates of P-glycoprotein (P-gp). We investigated the effect of arthritis on the hepatic and intestinal P-gp activity in rats, and substantiated the expression level of the hepatic P-gp. Doxorubicin was used as a P-gp substrate. Cumulative biliary excretion and intestinal exsorption of doxorubicin following intravenous administration were compared between adjuvant arthritis (AA) and normal rats. Intestinal P-gp activity was also investigated by intestinal everted sac method, and hepatic P-gp was detected by FITC-labeled antibody and visualized using a confocal laser microscope system. Biliary clearance of doxorubicin in AA rats was significantly decreased from that in normal rats. The expression level of the hepatic P-gp in AA rats was very low compared to normal rats, indicating down-regulation. Intestinal exsorption clearance was not different between AA and normal rats. Permeability of doxorubicin across intestinal everted sac was comparable between AA and normal rats, corresponding to in vivo study. In AA rats, hepatic P-gp activity was decreased due to the reduction of expression level, but intestinal P-gp activity was not changed. Different regulation systems may be involved in liver and intestine. PMID:12113888

  18. CpG-DNA enhancement the immune elicited as adjuvant of foot- and- mouth disease vaccine

    OpenAIRE

    Morshedi, A.; Daghighi, M.; Mahravani, H.

    2010-01-01

    In the present study the effect of the locally produced genetic adjuvant of ginea pig specific CpG-motif-containing oligodeoxynucleotide (CpG-ODN) in an inactivated FMD virus vaccine was evaluated. Boosting the ginea pigs with FMD vaccine along with CpG-ODN adjuvant produced relatively higher ratio (5-fold) of FMDV-specific IgG2a / IgG1 than those vaccinated in the absence of CpG-ODN. The neutralizing antibody (NA) titer induced by FMD vaccine along with CpG-ODN adjuvant was significantly hig...

  19. Changing Adjuvant Breast-Cancer Therapy with a Signal for Prevention.

    OpenAIRE

    Chlebowski, RT; Budoff, MJ

    2016-01-01

    Five randomized, full-scale studies have reported that 10 years of adjuvant endocrine therapy is beneficial for postmenopausal women with hormone-receptor-positive breast cancer. However, no prior study has involved more than 5 years of aromatase-inhibitor use or assessed a duration of adjuvant endocrine therapy of more than 10 years.(1) Goss and colleagues(2) now provide results from the MA.17R trial supporting the use of an aromatase inhibitor for 10 years and the use of adjuvant endocrine ...

  20. Application of radio-detoxified endotoxin as adjuvant for experimental foot-and-mouth disease vaccine

    International Nuclear Information System (INIS)

    The immunity enhancing adjuvant activity of radiodetoxified endotoxin (RD-LPS) on the potency of 'C' type foot-and-mouth (FMD) vaccine was tested in different animal species. For radiodetoxification 5 Mrad gamma radiation was used. The suitable quantity of RD-LSP (20 μg per mouse) adjuvated FMD vaccines of lower antigen content better than those of higher one. In cattle and sheep the adjuvant effect of oil + RD + LPS surpassed only slightly that of oil alone. The effect of RD-LPS in pig was very pronounced when applied in small doses but further studies in larger animal populations have to confirm this result. (author)

  1. Estrogen receptor, Progesterone receptor, HER2 status and Ki67 index and responsiveness to adjuvant tamoxifen in postmenopausal high-risk breast cancer patients enrolled in the DBCG 77C trial

    DEFF Research Database (Denmark)

    Knoop, Ann S; Lænkholm, Anne-Vibeke; Jensen, Maj-Britt;

    2014-01-01

    Background The DBCG 77C trial compared one year of tamoxifen in postmenopausal, steroid-receptor unknown, high-risk breast cancer patients to no adjuvant systemic therapy. After a potential follow-up of 30 years we report overall efficacy of the study and results according to subtypes subsequentl...

  2. Liposome-based polymer complex as a novel adjuvant: enhancement of specific antibody production and isotype switch

    Directory of Open Access Journals (Sweden)

    Chen CH

    2012-02-01

    Full Text Available Chia-Hung Chen1,*, Yu-Ling Lin1,*, Yen-Ku Liu1, Pei-Juin He2, Ching-Min Lin1, Yi-Han Chiu2, Chang-Jer Wu3, Tian-Lu Cheng4, Shih-Jen Liu5,6,**, Kuang-Wen Liao1,2,**1Institute of Molecular Medicine and Bioengineering, 2Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 3Department of Food Science, National Taiwan Ocean University, Keelung, 4Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 5National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, 6Graduate Institute of Immunology, China Medical University, Taichung, Taiwan, , *Chia-Hung Chen and Yu-Ling Lin contributed equally to this work**Kuang-Wen Liao and Shih-Jen Liu contributed equally to this workAbstract: The aim of vaccination is to induce appropriate immunity against pathogens. Antibody-mediated immunity is critical for protection against many virus diseases, although it is becoming more evident that coordinated, multifunctional immune responses lead to the most effective defense. Specific antibody (Ab isotypes are more efficient at protecting against pathogen invasion in different locations in the body. For example, compared to other Ab isotypes, immunoglobulin (Ig A provides more protection at mucosal areas. In this study, we developed a cationic lipopolymer (liposome-polyethylene glycol-polyethyleneimine complex [LPPC] adjuvant that strongly adsorbs antigens or immunomodulators onto its surface to enhance or switch immune responses. The results demonstrate that LPPC enhances uptake ability, surface marker expression, proinflammatory cytokine release, and antigen presentation in mouse phagocytes. In contrast to Freund's adjuvant, LPPC preferentially activates Th1-immunity against antigens in vivo. With lipopolysaccharides or CpG oligodeoxynucleotides, LPPC dramatically enhances the IgA or IgG2A proportion of total Ig, even in hosts that have developed

  3. Nanolipoprotein Particles (NLPs) as Versatile Vaccine Platforms for Co-delivery of Multiple Adjuvants with Subunit Antigens from Burkholderia spp. and F. tularensis - Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, N. O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-01-13

    The goal of this proposal is to demonstrate that colocalization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. In the third quarter of the third year, F344 rats vaccinated with adjuvanted NLP formulations were challenged with F. tularensis SCHU S4 at Battelle. Preliminary data indicate that up to 65% of females vaccinated intranasally with an NLP-based formulation survived this challenge, compared to only 20% survival of naïve animals. In addition, NLPs were successfully formulated with Burkholderia protein antigens. IACUC approval for immunological assessments in BALB/c mice was received and we anticipate that these assessments will begin by March 2015, pending ACURO approval.

  4. Immune response after one or two doses of pandemic influenza A (H1N1) monovalent, AS03-adjuvanted vaccine in HIV infected adults

    DEFF Research Database (Denmark)

    Bybeck Nielsen, Allan; Nielsen, Henriette Schjønning; Nielsen, Lars;

    2012-01-01

    INTRODUCTION: Continued research is needed to evaluate and improve the immunogenicity of influenza vaccines in HIV infected patients. We aimed to determine the antibody responses after one or two doses of the AS03-adjuvanted pandemic influenza A (H1N1) vaccine in HIV infected patients. METHOD......: Following the influenza season 2009/2010, 219 HIV infected patients were included and divided into three groups depending on whether they received none (n=60), one (n=31) or two (n=128) doses of pandemic influenza A (H1N1) vaccine. At inclusion, antibody titers for all patients were analyzed and compared.......7% and seroconversion rate of 86.7%. CONCLUSION: A single dose of AS03-adjuvanted pandemic influenza A (H1N1) vaccine created an adequate immune response in HIV infected patients lasting as long as 4-9 months. Two doses improved the immunogenicity further....

  5. Tratamento adjuvante nos GISTs Adjuvant treatment in GISTs

    Directory of Open Access Journals (Sweden)

    Laercio Gomes Lourenço

    2011-09-01

    Full Text Available INTRODUÇÃO: O tumor estromal gastrointestinal (GIST é o sarcoma mais comum do aparelho digestivo. Essa neoplasia ocorre devido à mutação do gene KIT com consequente ativação constitutiva da proteína KIT. O tratamento primário é cirúrgico e consiste na sua ressecção completa. Entretanto, alguns grupos de pacientes apresentam risco elevado de recorrência mesmo após operação com ressecção completa (R0, indicando diferenças no comportamento biológico. Estudos clínicos comprovaram a atividade clínica do mesilato de imatinibe, fazendo dele a primeira linha de tratamento padrão nos GISTs metastáticos ou irressecáveis, mudando muito o desfecho clínico dessa doença em relação aos benefícios anteriormente obtidos com a quimioterapia antineoplásica. MÉTODO: Foi realizada revisão da literatura com consulta nos periódicos das bases Medline/Pubmed, Scielo e Lilacs cruzando os descritores: tumor estromal gastrointestinal, Gist, tratamento, adjuvância. Além desta revisão foi adicionada a experiência pessoal dos autores. CONCLUSÃO: Melhor refinamento dos critérios de prognóstico tem permitido selecionar de forma mais adequada pacientes para o tratamento adjuvante com imatinibe. Os resultados de maior evidência até o momento respaldam o tratamento adjuvante por um ano, o que produz benefício significativo na sobrevida livre de recidiva, mas não na sobrevida global desses pacientes.INTRODUCTION: Gastrointestinal stromal tumor (GIST is the most common sarcoma of the digestive tract. This cancer occurs due to mutation of the KIT gene resulting in constitutive activation of KIT protein. The primary treatment is surgical and consists of complete resection. However, some groups of patients at high risk of recurrence even after surgery with complete resection (R0, indicate differences in biological behavior. Clinical studies have demonstrated the clinical activity of imatinib mesylate, making it the standard first

  6. Adjuvant whole abdominal radiotherapy in epithelial cancer of the ovary

    International Nuclear Information System (INIS)

    Purpose: To reexamine the use of adjuvant radiotherapy in optimally debulked patients. Methods and Materials: Between January 1985 and April 1998, 60 patients were treated with adjuvant whole abdominal radiotherapy (A-WART). The stage distribution was Stage IC in 17 patients, Stage II in 9, and Stage III in 34. The grade distribution was Grade 1 in 9 patients, Grade 2 in 27, and Grade 3 in 24; thus, 60% of the patients had Stage III disease and 40% had Grade 3 tumors. After surgery, no residuum was left in 42 (70%), ≤2 cm in 13 (22%), and >2 cm in 5 (8%) of 60 patients. Of the 60 patients, 19 also received platinum-based chemotherapy; in 12 of the 19, the chemotherapy was before A-WART. Thirty-seven of the patients had undergone previous abdominal procedures and a second-look operation was performed in 25% of them. A-WART consisted of 22 Gy in 22 fractions, at 5 fractions weekly in 90% of the patients. The remaining 10% received 25 Gy in 25 fractions within 5 weeks. The A-WART was delivered using a 4-MV linear accelerator. After abdominal irradiation, a boost to the pelvis was given to reach 45 Gy at 1.8 cGy/fraction, using a 4-15-MV linear accelerator. Results: Treatment was delivered in a median of 50 days (range 48-70). In 12 (20%) of the 60 patients, a transient treatment interruption occurred because of acute toxicity, mainly vomiting and diarrhea. The overall survival rate was 55% at 5 years (median follow-up 96.5 months). Patients with low-histologic grade tumors (Grade 1-2) had a better 5-year survival rate (66%) than those with Grade 3 tumors (35%; p<0.03). A tendency for better survival was found for those with Stage I-II than for those with Stage III (69% vs. 43%). Nonetheless, this difference did not reach statistical significance (p 0.17). For patients receiving chemotherapy, the 5-year survival rate was 51%, not statistically different from the 58% 5-year survival rate observed among those patients without adjuvant chemotherapy (p=0.9). The

  7. In vivo evaluation of early disease progression by X-ray phase-contrast imaging in the adjuvant-induced arthritic rat

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yongqiang; Xiong, Zhuang; Lv, Yizhong; Qian, Yinfeng [First Affiliated Hospital of Anhui Medical University, Department of Radiology, Hefei (China); Jiang, Shiping [University of Science and Technology of China, Synchrotron Radiation Laboratory, Hefei (China); Tian, Yulian [Institute of High Energy Physics, Chinese Academy of Science, Synchrotron Radiation Laboratory, Beijing (China)

    2006-03-15

    To study the early change of bone matrix and soft tissue around articulation in adjuvant-induced arthritic (AIA) rats non-invasively by X-ray phase-contrast imaging (XPCI), a new imaging method. Adjuvant-induced arthritis was established in male Sprague-Dawley (SD) rats (n=6, age 40 days) by subcutaneous injection of Freund's complete adjuvant (FCA) into the left hindpaw. In vivo XPCI evaluation of the early soft tissue and bone changes in AIA rats was consecutively performed and correlated with changes in volumes of right hindpaws and body weights. In comparison, the changes in the AIA rats were also evaluated with absorption-contrast imaging using the same X-ray source as XPCI and conventional radiography at the same time. After the imaging evaluation, AIA rats were subjected to histological examination. There was significant difference between the score of XPCI and the other two methods in demonstrating soft tissue (P<0.01), bone details (P<0.01) and lesions (P<0.001). By day 10 after subcutaneous injection of FCA, bone changes in the right hindpaw were not obvious, but swelling of soft tissue appeared. By day 12, bone erosion in the articular facet and the area around the articular facet, was detected, along with osteoporosis, and swelling of soft tissue was aggravated. By day 14 bone erosions became fused and expanded, especially in the margin area around the articular facet. At day 16 bone erosion still existed. Joint interspaces seemed wider than normal, and swelling of soft tissue was significant. By day 18 periosteal new bone formation was seen definitely, destruction of bone decreased, bone density around the articular was enhanced, and swelling of soft tissue was relieved. XPCI could clearly distinguish all these alterations, which could not be demonstrated by absorption-contrast imaging and conventional radiography. During the test period, the volume of the right hindpaw and the body weight of the AIA rats also changed significantly compared with

  8. Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice.

    Directory of Open Access Journals (Sweden)

    Li Song

    Full Text Available In spring 2013, human infections with a novel avian influenza A (H7N9 virus were reported in China. The number of cases has increased with over 200 mortalities reported to date. However, there is currently no vaccine available for the H7 subtype of influenza A virus. Virus-specific cellular immune responses play a critical role in virus clearance during influenza infection. In this study, we undertook a side-by-side evaluation of two different adjuvants, Salmonella typhimurium flagellin (fliC and polyethyleneimine (PEI, through intraperitoneal administration to assess their effects on the immunogenicity of the recombinant HA1-2 subunit vaccine of H7N9 influenza. The fusion protein HA1-2-fliC and HA1-2 combined with PEI could induce significantly higher HA1-2-specific IgG and hemagglutination inhibition titers than HA1-2 alone at 12 days post-boost, with superior HA1-2 specific IgG titers in the HA1-2-fliC group compared with the PEI adjuvanted group. The PEI adjuvanted vaccine induced higher IgG1/IgG2a ratio and significantly increased numbers of IFN-γ- and IL-4-producing cells than HA1-2 alone, suggesting a mixed Th1/Th2-type cellular immune response with a Th2 bias. Meanwhile, the HA1-2-fliC induced higher IgG2a and IgG1 levels, which is indicative of a mixed Th1/Th2-type profile. Consistent with this, significant levels, and equal numbers, of IFN-γ- and IL-4-producing cells were detected after HA1-2-fliC vaccination. Moreover, the marked increase in CD69 expression and the proliferative index with the HA1-2-fliC and PEI adjuvanted vaccines indicated that both adjuvanted vaccine candidates effectively induced antigen-specific cellular immune responses. Taken together, our findings indicate that the two adjuvanted vaccine candidates elicit effective and HA1-2-specific humoral and cellular immune responses, offering significant promise for the development of a successful recombinant HA1-2 subunit vaccine for H7N9 influenza.

  9. Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice.

    Science.gov (United States)

    Song, Li; Xiong, Dan; Hu, Maozhi; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

    2016-01-01

    In spring 2013, human infections with a novel avian influenza A (H7N9) virus were reported in China. The number of cases has increased with over 200 mortalities reported to date. However, there is currently no vaccine available for the H7 subtype of influenza A virus. Virus-specific cellular immune responses play a critical role in virus clearance during influenza infection. In this study, we undertook a side-by-side evaluation of two different adjuvants, Salmonella typhimurium flagellin (fliC) and polyethyleneimine (PEI), through intraperitoneal administration to assess their effects on the immunogenicity of the recombinant HA1-2 subunit vaccine of H7N9 influenza. The fusion protein HA1-2-fliC and HA1-2 combined with PEI could induce significantly higher HA1-2-specific IgG and hemagglutination inhibition titers than HA1-2 alone at 12 days post-boost, with superior HA1-2 specific IgG titers in the HA1-2-fliC group compared with the PEI adjuvanted group. The PEI adjuvanted vaccine induced higher IgG1/IgG2a ratio and significantly increased numbers of IFN-γ- and IL-4-producing cells than HA1-2 alone, suggesting a mixed Th1/Th2-type cellular immune response with a Th2 bias. Meanwhile, the HA1-2-fliC induced higher IgG2a and IgG1 levels, which is indicative of a mixed Th1/Th2-type profile. Consistent with this, significant levels, and equal numbers, of IFN-γ- and IL-4-producing cells were detected after HA1-2-fliC vaccination. Moreover, the marked increase in CD69 expression and the proliferative index with the HA1-2-fliC and PEI adjuvanted vaccines indicated that both adjuvanted vaccine candidates effectively induced antigen-specific cellular immune responses. Taken together, our findings indicate that the two adjuvanted vaccine candidates elicit effective and HA1-2-specific humoral and cellular immune responses, offering significant promise for the development of a successful recombinant HA1-2 subunit vaccine for H7N9 influenza.

  10. Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus glycoprotein (GP) nanoparticle vaccine in mice.

    Science.gov (United States)

    Bengtsson, Karin Lövgren; Song, Haifeng; Stertman, Linda; Liu, Ye; Flyer, David C; Massare, Michael J; Xu, Ren-Huan; Zhou, Bin; Lu, Hanxin; Kwilas, Steve A; Hahn, Timothy J; Kpamegan, Eloi; Hooper, Jay; Carrion, Ricardo; Glenn, Gregory; Smith, Gale

    2016-04-01

    Ebola virus (EBOV) causes severe hemorrhagic fever for which there is no approved treatment or preventive vaccine. Immunological correlates of protective immunity against EBOV disease are not well understood. However, non-human primate studies have associated protection of experimental vaccines with binding and neutralizing antibodies to the EBOV glycoprotein (GP) as well as EBOV GP-specific CD4(+) and CD8(+) T cells. In this report a full length, unmodified Zaire EBOV GP gene from the 2014 EBOV Makona strain (EBOV/Mak) was cloned into a baculovirus vector. Recombinant EBOV/Mak GP was produced in Sf9 insect cells as glycosylated trimers and, when purified, formed spherical 30-40 nm particles. In mice, EBOV/Mak GP co-administered with the saponin adjuvant Matrix-M was significantly more immunogenic, as measured by virus neutralization titers and anti-EBOV/Mak GP IgG as compared to immunization with AlPO4 adjuvanted or non-adjuvanted EBOV/Mak GP. Similarly, antigen specific T cells secreting IFN-γ were induced most prominently by EBOV/Mak GP with Matrix-M. Matrix-M also enhanced the frequency of antigen-specific germinal center B cells and follicular helper T (TFH) cells in the spleen in a dose-dependent manner. Immunization with EBOV/Mak GP with Matrix-M was 100% protective in a lethal viral challenge murine model; whereas no protection was observed with the AlPO4 adjuvant and only 10% (1/10) mice were protected in the EBOV/Mak GP antigen alone group. Matrix-M adjuvanted vaccine induced a rapid onset of specific IgG and neutralizing antibodies, increased frequency of multifunctional CD4+ and CD8(+) T cells, specific TFH cells, germinal center B cells, and persistence of EBOV GP-specific plasma B cells in the bone marrow. Taken together, the addition of Matrix-M adjuvant to the EBOV/Mak GP nanoparticles enhanced both B and T-cell immune stimulation which may be critical for an Ebola subunit vaccine with broad and long lasting protective immunity.

  11. Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus glycoprotein (GP) nanoparticle vaccine in mice.

    Science.gov (United States)

    Bengtsson, Karin Lövgren; Song, Haifeng; Stertman, Linda; Liu, Ye; Flyer, David C; Massare, Michael J; Xu, Ren-Huan; Zhou, Bin; Lu, Hanxin; Kwilas, Steve A; Hahn, Timothy J; Kpamegan, Eloi; Hooper, Jay; Carrion, Ricardo; Glenn, Gregory; Smith, Gale

    2016-04-01

    Ebola virus (EBOV) causes severe hemorrhagic fever for which there is no approved treatment or preventive vaccine. Immunological correlates of protective immunity against EBOV disease are not well understood. However, non-human primate studies have associated protection of experimental vaccines with binding and neutralizing antibodies to the EBOV glycoprotein (GP) as well as EBOV GP-specific CD4(+) and CD8(+) T cells. In this report a full length, unmodified Zaire EBOV GP gene from the 2014 EBOV Makona strain (EBOV/Mak) was cloned into a baculovirus vector. Recombinant EBOV/Mak GP was produced in Sf9 insect cells as glycosylated trimers and, when purified, formed spherical 30-40nm particles. In mice, EBOV/Mak GP co-administered with the saponin adjuvant Matrix-M was significantly more immunogenic, as measured by virus neutralization titers and anti-EBOV/Mak GP IgG as compared to immunization with AlPO4 adjuvanted or non-adjuvanted EBOV/Mak GP. Similarly, antigen specific T cells secreting IFN-γ were induced most prominently by EBOV/Mak GP with Matrix-M. Matrix-M also enhanced the frequency of antigen-specific germinal center B cells and follicular helper T (TFH) cells in the spleen in a dose-dependent manner. Immunization with EBOV/Mak GP with Matrix-M was 100% protective in a lethal viral challenge murine model; whereas no protection was observed with the AlPO4 adjuvant and only 10% (1/10) mice were protected in the EBOV/Mak GP antigen alone group. Matrix-M adjuvanted vaccine induced a rapid onset of specific IgG and neutralizing antibodies, increased frequency of multifunctional CD4+ and CD8(+) T cells, specific TFH cells, germinal center B cells, and persistence of EBOV GP-specific plasma B cells in the bone marrow. Taken together, the addition of Matrix-M adjuvant to the EBOV/Mak GP nanoparticles enhanced both B and T-cell immune stimulation which may be critical for an Ebola subunit vaccine with broad and long lasting protective immunity. PMID:26921779

  12. The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy

    Directory of Open Access Journals (Sweden)

    Park Cheol

    2011-08-01

    Full Text Available Abstract Background Colorectal carcinoma (CRC with CpG island methylator phenotype (CIMP is recognized as a distinct subgroup of CRC, and CIMP status affects prognosis and response to chemotherapy. Identification of CIMP status in CRC is important for proper patient management. In Eastern countries, however, the clinicopathologic and molecular characteristics and prognosis of CRCs with CIMP are still unclear. Methods A total of 245 patients who underwent their first surgical resection for sporadic CRC were enrolled and CIMP status of the CRCs was determined using the quantitative MethyLight assay. The clinicopathologic and molecular characteristics were reviewed and compared according to CIMP status. In addition, the three-year recurrence-free survival (RFS of 124 patients with stage II or stage III CRC was analyzed in order to assess the effectiveness of fluoropyrimidine-based adjuvant chemotherapy with respect to CIMP status. Results CIMP-high CRCs were identified in 34 cases (13.9%, and were significantly associated with proximal tumor location, poorly differentiated carcinoma, mucinous histology, and high frequencies of BRAF mutation, MGMT methylation, and MSI-high compared to CIMP-low/negative carcinomas. For patients with stage II or III CIMP-low/negative CRCs, no significant difference was found in RFS between those undergoing surgery alone and those receiving surgery with fluoropyrimidine-based adjuvant chemotherapy. However, for patients with CIMP-high CRCs, patients undergoing surgery with fluoropyrimidine-based adjuvant chemotherapy (n = 17; three-year RFS: 100% showed significantly better RFS than patients treated with surgery alone (n = 7; three-year RFS: 71.4% (P = 0.022. Conclusions Our results suggest that selected patients with CIMP-high CRC may benefit from fluoropyrimidine-based adjuvant chemotherapy with longer RFS. Further large scale-studies are required to confirm our results.

  13. Immunogenicity of a virosomally-formulated Plasmodium falciparum GLURP-MSP3 chimeric protein-based malaria vaccine candidate in comparison to adjuvanted formulations

    Directory of Open Access Journals (Sweden)

    Tamborrini Marco

    2011-12-01

    Full Text Available Abstract Background In clinical trials, immunopotentiating reconstituted influenza virosomes (IRIVs have shown great potential as a versatile antigen delivery platform for synthetic peptides derived from Plasmodium falciparum antigens. This study describes the immunogenicity of a virosomally-formulated recombinant fusion protein comprising domains of the two malaria vaccine candidate antigens MSP3 and GLURP. Methods The highly purified recombinant protein GMZ2 was coupled to phosphatidylethanolamine and the conjugates incorporated into the membrane of IRIVs. The immunogenicity of this adjuvant-free virosomal formulation was compared to GMZ2 formulated with the adjuvants Montanide ISA 720 and Alum in three mouse strains with different genetic backgrounds. Results Intramuscular injections of all three candidate vaccine formulations induced GMZ2-specific antibody responses in all mice tested. In general, the humoral immune response in outbred NMRI mice was stronger than that in inbred BALB/c and C57BL/6 mice. ELISA with the recombinant antigens demonstrated immunodominance of the GLURP component over the MSP3 component. However, compared to the Al(OH3-adjuvanted formulation the two other formulations elicited in NMRI mice a larger proportion of anti-MSP3 antibodies. Analyses of the induced GMZ2-specific IgG subclass profiles showed for all three formulations a predominance of the IgG1 isotype. Immune sera against all three formulations exhibited cross-reactivity with in vitro cultivated blood-stage parasites. Immunofluorescence and immunoblot competition experiments showed that both components of the hybrid protein induced IgG cross-reactive with the corresponding native proteins. Conclusion A virosomal formulation of the chimeric protein GMZ2 induced P. falciparum blood stage parasite cross-reactive IgG responses specific for both MSP3 and GLURP. GMZ2 thus represents a candidate component suitable for inclusion into a multi-valent virosomal

  14. Transcutaneous electrical nerve stimulation therapy: An adjuvant pain controlling modality in TMD patients - A clinical study

    Directory of Open Access Journals (Sweden)

    Muhammad Shanavas

    2014-01-01

    Conclusion: The observed data suggest that TENS therapy can be used as an adjuvant modality in the management of pain associated with TMDs. This study justifies the use of TENS therapy in the management of TMD.

  15. Novel adjuvant formulations for delivery of anti-tuberculosis vaccine candidates.

    Science.gov (United States)

    Agger, Else Marie

    2016-07-01

    There is an urgent need for a new and improved vaccine against tuberculosis for controlling this disease that continues to pose a global health threat. The current research strategy is to replace the present BCG vaccine or boost BCG-immunity with subunit vaccines such as viral vectored- or protein-based vaccines. The use of recombinant proteins holds a number of production advantages including ease of scalability, but requires an adjuvant inducing cell-mediated immune responses. A number of promising novel adjuvant formulations have recently been designed and show evidence of induction of cellular immune responses in humans. A common trait of effective TB adjuvants including those already in current clinical testing is a two-component approach combining a delivery system with an appropriate immunomodulator. This review summarizes the status of current TB adjuvant research with a focus on the division of labor between delivery systems and immunomodulators. PMID:26596558

  16. POLYPRENYL PHOSPHATES AS ADJUVANTS, POLARIZING THE IMMUNE RESPONSE TO Th1

    Directory of Open Access Journals (Sweden)

    A. V. Pronin

    2012-01-01

    Full Text Available Abstract. The attempts to decrease a toxic action of Freund complete adjuvant have led to development of new emulsion adjuvant compositions. More often they are based on metabolizable oil (squalene with addition the Tween 80 (Polisorbate 80 as an emulsifier. The third component is an immunomodulator. Adjuvants, intended for prevention of virus infections, should include the immunomodulators polarizing the immune response to Th1. From this point of view adjuvant based on a colloidal solution prepared by means of the Tween 80 from polyprenyl phasphates of fir needles (Phosprenyl can be rather perspective. The last one, as well as squalene, is constructed by isoprene links, but has them not 6, but 16 that essentially reduces its toxicity. The obtained data shows that Phosprenyl essentially enhances efficiency of vaccination in such virus infections as tick born encephalitis, bird flu, poliomyelitis and polarizes the immune response to Th1.

  17. Adjuvants Based on Hybrid Antibiotics Overcome Resistance in Pseudomonas aeruginosa and Enhance Fluoroquinolone Efficacy.

    Science.gov (United States)

    Gorityala, Bala Kishan; Guchhait, Goutam; Fernando, Dinesh M; Deo, Soumya; McKenna, Sean A; Zhanel, George G; Kumar, Ayush; Schweizer, Frank

    2016-01-11

    The use of adjuvants that rescue antibiotics against multidrug-resistant (MDR) pathogens is a promising combination strategy for overcoming bacterial resistance. While the combination of β-lactam antibiotics and β-lactamase inhibitors has been successful in restoring antibacterial efficacy in MDR bacteria, the use of adjuvants to restore fluoroquinolone efficacy in MDR Gram-negative pathogens has been challenging. We describe tobramycin-ciprofloxacin hybrid adjuvants that rescue the activity of fluoroquinolone antibiotics against MDR and extremely drug-resistant Pseudomonas aeruginosa isolates in vitro and enhance fluoroquinolone efficacy in vivo. Structure-activity studies reveal that the presence of both tobramycin and ciprofloxacin, which are separated by a C12 tether, is critical for the function of the adjuvant. Mechanistic studies indicate that the antibacterial modes of ciprofloxacin are retained while the role of tobramycin is limited to destabilization of the outer membrane in the hybrid.

  18. Randomized controlled trial of adjuvant oral dexamethasone pulse therapy in pemphigus vulgaris - PEMPULS trial

    NARCIS (Netherlands)

    Mentink, LF; Mackenzie, MW; Toth, GG; Laseur, M; Lambert, FPG; Veeger, NJGM; Cianchini, G; Pavlovic, MD; Jonkman, MF

    2006-01-01

    Objective: To determine the therapeutic effect of adjuvant dexamethasone pulse therapy when given in addition to conventional treatment of pemphigus vulgaris. Design: A randomized, placebo-controlled trial. Setting: International European, multicenter outpatient and inpatient study. Patients: Of the

  19. Antiepileptic, behavioral, and antidepressant effects of adjuvant lamotrigine therapy in drug-resistant epilepsy

    Directory of Open Access Journals (Sweden)

    Martinović Žarko J.

    2004-01-01

    Full Text Available Aim. To evaluate the behavioral effects of lamotrigine as add-on therapy in treatment-resistant epilepsy. Methods. An open, prospective, long-term study of lamotrigine as adjuvant therapy was performed in 56 patients with drug-resistant epilepsy (female/male ratio 35/21, age range 16-51 years. All the patients kept seizure diaries, and electroencephalograms were recorded at baseline and during 24 months of the treatment. Quality of life questionnaire, Hamilton depression scale (HMD, Beck depression scale (BDI, and Hamilton anxiety scale (HMA were used before and during lamotrigine therapy. Comparative assessments were made in an age- and sex-matched control group treated with other antiepileptic drugs. Results. Overall, seizure control was improved in 55.3% of the patients, remained unchanged in 39.3%, and deteriorated in 5.4%. Improvement in some quality of life measures occurred in 50% of the patients. The HMD subscales and BDI scale showed significant improvement in lamotrigine treated patients compared to the control group (ANOVA, p < 0.01. Negative behavioral effects occurred in 10.7% of the patients. Conclusion. Lamotrigine demonstrated significant antiepileptic long-term efficacy, and its positive effects on the mood and quality of life, which surpassed the negative behavioral effects, and contributed highly to the favorable treatment outcome.

  20. The Efficacy of Intranasal Desmopressin as an Adjuvant in the Acute Renal Colic Pain Management

    Directory of Open Access Journals (Sweden)

    Kambiz Masoumi

    2014-01-01

    Full Text Available The aim of this study was to compare analgesic effect of intramuscular (IM sodium diclofenac and intranasal desmopressin combination with IM sodium diclofenac alone in patients with acute renal colic. In this randomized double-blind clinical trial, all patients aged 18 to 55 years who were diagnosed as acute renal colic and met the inclusion and exclusion criteria were randomized into two groups to receive 40 μg intranasal desmopressin spray and 75 mg IM sodium diclofenac combination (Group A or 75 mg IM sodium diclofenac alone (Group B. The pain score of patients was assessed using a visual analogue scale (VAS at baseline, 15, 30, 45, and 60 minutes after administration. Of all 159 patients who were assessed for eligibility finally, the results of 120 patients were analyzed. There was no significant difference regarding age and gender between two groups. The baseline VAS score was not significantly different between two groups (P=0.44. The Mean ± SD scores of two groups reduced 15 minutes after drug administration, but this decrease was significantly more in Group A compared with Group B (P=0.02. This pattern continued in minutes 30, 45, and 60 of drug administration. Our results showed that desmopressin could be used as an effective adjuvant in acute renal colic pain management.

  1. Role of adjuvant chemoradiotherapy in treatment of resectable esophageal carcinoma: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    ZHENG Bin; ZHENG Wei; ZHU Yong; LIN Xiao-yan; XU Ben-hua; CHEN Chun

    2013-01-01

    Background The effectiveness and influence of surgery followed by adjuvant chemoradiotherapy (CRT) on the survival of patients with resectable esophageal carcinoma are still under debate.The outcomes of clinical trials have not been consistent.This study aimed to perform a meta-analysis of eligible published clinical trials to compare CRT with surgery without adjuvant chemoradiotherapy (non-CRT) for resectable esophageal carcinoma.Methods Computerized bibliographic and manual searches were undertaken to identify all eligible literature between 1990 and 2012.PubMed,EMBASE,Chinese National Knowledge Infrastructure,and Wanfang databases were our primary sources for published clinical trials.The quality of the methodology and reliability of the data from all of the clinical trials were assessed.All data were extracted by three independent researchers.Results Seven studies that included a total of 523 patients were selected.It was found that CRT significantly improved survival.The odds ratio (OR) in comparing CRT and non-CRT groups was 1.75 (95% confidence intervals (CI):1.17-2.60,P=0.006) for 1-year survival,2.07 (95% Cl:1.45-2.96,P <0.0001) for 3-year survival,and 2.17 (95% CI:1.45-3.26,P=0.0002) for 5-year survival.There have been no CRT treatment-related deaths reported in the literature.The incidence of related complications was high in the cases with CRT.Patients treated with CRT had a lower incidence of local-regional cancer recurrence (OR:0.49,95% Cl:0.31-0.76,P=0.002) and a similar incidence of distant cancer recurrence (OR:0.90,95% CI:0.60-1.34,P=0.60).Conclusions It was found that patients with resectable esophageal carcinoma could gain a survival benefit from CRT.However,CRT was associated with a high incidence of related complications.

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

    OpenAIRE

    Martins, Karen A O; Christopher L Cooper; Stronsky, Sabrina M.; Sarah L.W. Norris; Steven A Kwilas; Jesse T. Steffens; Benko, Jacqueline G.; van Tongeren, Sean A.; Sina Bavari

    2016-01-01

    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 fro...

  3. Effectiveness of electrochemotherapy after IFN-α adjuvant therapy of melanoma patients

    Directory of Open Access Journals (Sweden)

    Hribernik Andrejc

    2016-03-01

    Full Text Available The combination of electrochemotherapy with immuno-modulatory treatments has already been explored and proven effective. However, the role of interferon alpha (IFN-α adjuvant therapy of melanoma patients and implication on electrochemotherapy effectiveness has not been explored yet. Therefore, the aim of the study was to retrospectively evaluate the effectiveness and safety of electrochemotherapy after the previous adjuvant treatment with IFN-α in melanoma patients.

  4. Adjuvant chemotherapy in stage I breast cancer. More harm than benefit.

    OpenAIRE

    Mueller, C B

    1993-01-01

    Clinical trials of adjuvant chemotherapy for breast cancer have shown a prolonged disease-free interval but no improvement in survival. This review of the evidence indicates that adjuvant therapy induces an antineoplastic drug resistance that makes "salvage" therapy less effective. The benefit that is seen only in group statistics, not in an individual, must be weighed against the harm an individual incurs from the chemotherapy.

  5. Autoimmune antibodies and recurrence-free interval in melanoma patients treated with adjuvant interferon

    DEFF Research Database (Denmark)

    Bouwhuis, Marna G; Suciu, Stefan; Collette, Sandra;

    2009-01-01

    BACKGROUND: Appearance of autoantibodies and clinical manifestations of autoimmunity in melanoma patients treated with adjuvant interferon (IFN)-alpha2b was reported to be associated with improved prognosis. We assessed the association of the appearance of autoantibodies after initiation of treat......BACKGROUND: Appearance of autoantibodies and clinical manifestations of autoimmunity in melanoma patients treated with adjuvant interferon (IFN)-alpha2b was reported to be associated with improved prognosis. We assessed the association of the appearance of autoantibodies after initiation...

  6. Adjuvant enhancement of humoral immune response to chemically inactivated bovine viral diarrhea virus.

    OpenAIRE

    Chen, K S; Johnson, D. W.; Muscoplat, C C

    1985-01-01

    Potentiation of the antibody response to inactivated bovine viral diarrhea virus by immunological adjuvants was studied in guinea pigs and cattle. The inactivated bovine viral diarrhea virus alone was demonstrated to be a weak immunogen. Addition of either 2 mg per mL diethylaminoethyl-dextran or 5% alhydrogel to inactivated bovine viral diarrhea virus did not or only slightly stimulated the antibody response; the combined adjuvants induced a significantly higher titer. A higher concentration...

  7. Adjuvant Effect of Cationic Liposomes for Subunit Influenza Vaccine: Influence of Antigen Loading Method, Cholesterol and Immune Modulators

    Directory of Open Access Journals (Sweden)

    Alexander Kros

    2013-07-01

    Full Text Available Cationic liposomes are potential adjuvants for influenza vaccines. In a previous study we reported that among a panel of cationic liposomes loaded with influenza hemagglutinin (HA, DC-Chol:DPPC (1:1 molar ratio liposomes induced the strongest immune response. However, it is not clear whether the cholesterol (Chol backbone or the tertiary amine head group of DC-Chol was responsible for this. Therefore, in the present work we studied the influence of Chol in the lipid bilayer of cationic liposomes. Moreover, we investigated the effect of the HA loading method (adsorption versus encapsulation and the encapsulation of immune modulators in DC-Chol liposomes on the immunogenicity of HA. Liposomes consisting of a neutral lipid (DPPC or Chol and a cationic compound (DC-Chol, DDA, or eDPPC were produced by film hydration-extrusion with/without an encapsulated immune modulator (CpG or imiquimod. The liposomes generally showed comparable size distribution, zeta potential and HA loading. In vitro studies with monocyte-derived human dendritic cells and immunization studies in C57Bl/6 mice showed that: (1 liposome-adsorbed HA is more immunogenic than encapsulated HA; (2 the incorporation of Chol in the bilayer of cationic liposomes enhances their adjuvant effect; and (3 CpG loaded liposomes are more efficient at enhancing HA-specific humoral responses than plain liposomes or Alhydrogel.

  8. Urinary metabolite profiling provides potential differentiation to explore the mechanisms of adjuvant-induced arthritis in rats.

    Science.gov (United States)

    Jiang, Hui; Liu, Jian; Wang, Ting; Gao, Jia-Rong; Sun, Yue; Huang, Chuan-Bing; Meng, Mei; Qin, Xiu-Juan

    2016-09-01

    To explore the pathogenesis of rheumatoid arthritis (RA) from the perspective of metabolomics, gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) technology was used to observe changes in the metabolic profiles of urine output from rats with adjuvant-induced arthritis (AA). Sprague-Dawley rats were randomly divided into a control group and an experimental group, with eight in each. Rats in the experimental group were induced by intracutaneous innoculation of 0.1 mL Freund's complete adjuvant to right paws. On day 20 after immunization, the metabolic profiles between rat control and experimental groups were compared by combining GC-TOF/MS technology with multivariate statistical approaches, including principal component analysis, partial least squares discriminant analysis and orthogonal projections to latent structures-discriminant analysis. Nine potential biomarkers were identified, including 2,2-dimethylsuccinic acid, tartronic acid, dehydroshikimic acid, hippuric acid, adenine, phenaceturic acid, l-dopa, 1,4-dihydroxy-2-naphthoic acid and melibiose. The findings indicate that the rats with AA are disturbed in metabolism of purine, amino acid, fat and energy. This study also demonstrates that the dysfunction in a range of biosynthetic and catabolic pathways, which leads to increased oxygen free radicals and inflammation, could cause underlying pathogenesis of RA. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26856389

  9. Encapsulation and modified-release of thymol from oral microparticles as adjuvant or substitute to current medications.

    Science.gov (United States)

    Rassu, G; Nieddu, M; Bosi, P; Trevisi, P; Colombo, M; Priori, D; Manconi, P; Giunchedi, P; Gavini, E; Boatto, G

    2014-10-15

    The aim of this study was to encapsulate, thymol, in natural polymers in order to obtain (i) taste masking effect and, then, enhancing its palatability and (ii) two formulations for systemic and local delivery of herbal drug as adjuvants or substitutes to current medications to prevent and treat several human and animal diseases. Microspheres based on methylcellulose or hydroxypropyl methylcellulose phthalate (HPMCP) were prepared by spray drying technique. Microparticles were in vitro characterized in terms of yield of production, drug content and encapsulation efficiency, particle size, morphology and drug release. Both formulations were in vivo orally administered and pharmacokinetic analysis was carried out. The polymers used affect the release and, then, the pharmacokinetic profile of thymol. Encapsulation into methylcellulose microspheres leads to short half/life but bioavailability remarkably increases compared to the free thymol. In contrast, enteric formulation based on HPMCP shows very limited systemic absorption. These formulations could be proposed as alternative or adjuvants for controlling pathogen infections in human or animal. In particular, methylcellulose microspheres can be used for thymol systemic administration at low doses and HPMCP particles for local treatment of intestinal infections. PMID:25442269

  10. Effect of adjuvant argatroban therapy on neurological function, endothelial injury and inflammation state in patient with acute cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Nan Che

    2016-01-01

    Objective:To analyze the effect of adjuvant argatroban therapy on neurological function, endothelial injury and inflammation state in patient with acute cerebral infarction.Methods:A total of 118 patients with acute cerebral infarction were divided into observation group and control group according to the random number table, control group received conventional treatment, observation group received argatroban + conventional treatment, and then differences in TCD cerebral blood flow, serum neurological function, endothelial injury and inflammatory marker levels were compared between two groups after treatment.Results:TCD MCA and ACA values of observation group after treatment were higher than those of control group (P<0.05); serum neurological function indexes copeptin, NT-proBNP, PAO and S-100B levels of observation group after treatment were lower than those of control group, endothelial injury index ET-1 level was lower than that of control group, NO and CGRP levels were higher than those of control group, and inflammatory markers hs-CRP, TNF-α, IL-6, MMP-9 and Lp-PLA2 levels were lower than those of control group (P<0.05).Conclusions:Adjuvant argatroban therapy can optimize the overall condition in patients with acute cerebral infarction, and plays a positive role in improving the neurological function, reducing endothelial injury and inflammation state, etc.

  11. The mycobacterial cord factor adjuvant analogue trehalose-6,6'-dibehenate (TDB) activates the Nlrp3 inflammasome.

    Science.gov (United States)

    Schweneker, Katrin; Gorka, Oliver; Schweneker, Marc; Poeck, Hendrik; Tschopp, Jürg; Peschel, Christian; Ruland, Jürgen; Gross, Olaf

    2013-04-01

    The success of a vaccine consists in the induction of an innate immune response and subsequent activation of the adaptive immune system. Because antigens are usually not immunogenic, the addition of adjuvants that activate innate immunity is required. The mycobacterial cord factor trehalose-6,6'-dimycolate (TDM) and its synthetic adjuvant analogue trehalose-6,6'-dibehenate (TDB) rely on the C-type lectin Mincle and the signaling molecules Syk and Card9 to trigger innate immunity. In this study, we show that stimulation of bone marrow-derived dendritic cells (BMDCs) with TDB induces Nlrp3 inflammasome-dependent IL-1β secretion. While Card9 is required for NF-κB activation by TDB, it is dispensable for TDB-induced activation of the Nlrp3 inflammasome. Additionally, efflux of intracellular potassium, lysosomal rupture, and oxygen radical (ROS) production are crucial for caspase-1 processing and IL-1β secretion by TDB. In an in vivo inflammation model, we demonstrate that the recruitment of neutrophils by TDB is significantly reduced in the Nlrp3-deficient mice compared to the wild-type mice, while the production of chemokines in vitro is not influenced by the absence of Nlrp3. These results identify the Nlrp3 inflammasome as an essential mediator for the induction of an innate immune response triggered by TDB. PMID:22921586

  12. Inducible nitric oxide synthase and guinea-pig ileitis induced by adjuvant

    Directory of Open Access Journals (Sweden)

    N. D. Seago

    1995-01-01

    Full Text Available We sought to establish a model of inflammatory bowel disease by augmenting the activity of the local immune system with Freund's complete adjuvant, and to determine if inducible nitric oxide synthase (iNOS expression and peroxynitrite formation accompanied the inflammatory condition. In anaesthetized guinea-pigs, a loop of distal ileum received intraluminal 50% ethanol followed by Freund's complete adjuvant. Control animals were sham operated. When the animals were killed 7 or 14 days later, loop lavage fluid was examined for nitrite and PGE2 levels; mucosal levels of granulocyte and macrophages were estimated by myeloperoxidase (MPO and N-acetyl-D-glucosaminidase (NAG activity, respectively. Cellular localization if iNOS and peroxynitrite formation were determined by immunohistochemistry with polyclonal antibodies directed against peptide epitopes of mouse iNOS and nitrotyrosine, respectfully. Adjuvant administration resulted in a persistent ileitis, featuring gut thickening, crypt hyperplasia, villus tip swelling and disruption, and cellular infiltration. Lavage levels of PGE2 and nitrite were markedly elevated by adjuvant treatment. Immunoreactive iNOS and nitrotyrosine bordered on detectability in normal animals but were markedly evident with adjuvant treatment at day 7 and particularly day 14. Immunohistochemistry suggested that enteric neurons and epithelia were major sites of iNOS activity and peroxynitrite formation. We conclude that local administration of adjuvant establishes a chronic ileitis. Inducible nitric oxide synthase may contribute to the inflammatory process.

  13. Aluminum adjuvants of vaccines injected into the muscle: Normal fate, pathology and associated disease.

    Science.gov (United States)

    Gherardi, R K; Aouizerate, J; Cadusseau, J; Yara, S; Authier, F J

    2016-06-01

    Aluminum oxyhydroxide (Alhydrogel(®)) is a nano-crystalline compound forming aggregates that has been introduced in vaccine for its immunologic adjuvant effect in 1926. It is the most commonly used adjuvant in human and veterinary vaccines but mechanisms by which it stimulates immune responses remain ill-defined. Although generally well tolerated on the short term, it has been suspected to occasionally cause delayed neurologic problems in susceptible individuals. In particular, the long-term persistence of aluminic granuloma also termed macrophagic myofasciitis is associated with chronic arthromyalgias and fatigue and cognitive dysfunction. Safety concerns largely depend on the long biopersistence time inherent to this adjuvant, which may be related to its quick withdrawal from the interstitial fluid by avid cellular uptake; and the capacity of adjuvant particles to migrate and slowly accumulate in lymphoid organs and the brain, a phenomenon documented in animal models and resulting from MCP1/CCL2-dependant translocation of adjuvant-loaded monocyte-lineage cells (Trojan horse phenomenon). These novel insights strongly suggest that serious re-evaluation of long-term aluminum adjuvant phamacokinetics and safety should be carried out. PMID:26948677

  14. INTRASITE VANCOMYCIN POWDER AS A PROPHYLACTIC ADJUVANT IN LUMBAR FUSION

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    Jorge Álvaro González Ross

    2016-03-01

    Full Text Available ABSTRACT Objective: To identify whether the use of prophylactic intrasite vancomycin as an adjuvant is a protective factor against deep tissue infection of the surgical site. Methods: Retrospective, descriptive, case-control study evaluating 210 patients, of whom 70 received intrasite vancomycin (case group and 140 were controls. It was made a follow up for at least one year, reviewing the physical and electronic records. Data were tabulated in spreadsheets (Excel including all variables and the statistical analysis was made with Epi InfoTM 7 to calculate the odds ratio. Results: Seven cases of deep infection occurred in the control group and none was found in the case group (odds ratio [95% confidence interval]: 0.1262 [0.007-2.24], P = 0.1585. Among the predisposing factors, diabetes and surgical time were the most relevant. Conclusions: Intrasite use of vancomycin has a protective effect against deep infection in patients undergoing lumbar fusion surgery without presenting considerable side effects.

  15. Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma

    International Nuclear Information System (INIS)

    Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months' duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage 11 or 111 disease receives postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71% and 79%, respectively. Copyright (1998) Blackwell Science Pty Ltd

  16. Safety evaluation of monophosphoryl lipid A (MPL): an immunostimulatory adjuvant.

    Science.gov (United States)

    Baldrick, Paul; Richardson, Derek; Elliott, Gary; Wheeler, Alan W

    2002-06-01

    Animal models have shown the potential use of monophosphoryl lipid A (MPL), a detoxified bacterial lipopolysaccharide, as a vaccine adjuvant. Immunostimulatory activity with diverse effects on the cellular elements of the immune system has been demonstrated and a range of vaccines incorporating MPL, including allergy vaccines, are currently under clinical evaluation. A series of preclinical safety investigations was performed to support clinical use of MPL as used in allergy vaccines and comprised cardiovascular/respiratory assessment in dog (up to 100 microg/kg/day); repeat-dose toxicity in rat, rabbit, and dog (up to 2500 and 1200 microg/kg/day in the rat and dog, respectively); reproduction toxicity in rat and rabbit (up to 100 microg/kg/day); and genotoxicity studies. Overall, repeat-dose toxicity studies in the rat and dog showed expected immunostimulatory effects and/or signs of toxicity associated with overstimulation of the immune system (notably increased spleen weight and white blood cell values). Studies in the rabbit with weekly doses of MPL produced no effects. MPL was shown to have no adverse effects on cardiovascular/respiratory function, reproduction, and genotoxicity.

  17. Selective glucocorticoid receptor-activating adjuvant therapy in cancer treatments

    Science.gov (United States)

    Sundahl, Nora; Clarisse, Dorien; Bracke, Marc; Offner, Fritz; Berghe, Wim Vanden; Beck, Ilse M.

    2016-01-01

    Although adverse effects and glucocorticoid resistance cripple their chronic use, glucocorticoids form the mainstay therapy for acute and chronic inflammatory disorders, and play an important role in treatment protocols of both lymphoid malignancies and as adjuvant to stimulate therapy tolerability in various solid tumors. Glucocorticoid binding to their designate glucocorticoid receptor (GR), sets off a plethora of cell-specific events including therapeutically desirable effects, such as cell death, as well as undesirable effects, including chemotherapy resistance, systemic side effects and glucocorticoid resistance. In this context, selective GR agonists and modulators (SEGRAMs) with a more restricted GR activity profile have been developed, holding promise for further clinical development in anti-inflammatory and potentially in cancer therapies. Thus far, the research into the prospective benefits of selective GR modulators in cancer therapy limped behind. Our review discusses how selective GR agonists and modulators could improve the therapy regimens for lymphoid malignancies, prostate or breast cancer. We summarize our current knowledge and look forward to where the field should move to in the future. Altogether, our review clarifies novel therapeutic perspectives in cancer modulation via selective GR targeting.

  18. Adjuvant radiotherapy for pathologically advanced prostate cancer a randomized clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Ian, M.; Thompson, J.R.; Catherine, M.; Tangen, P.H.; Paradelo, J.; Scott Lucia, M.; Miller, G.; Troyer, D.; Messing, E.; Forman, J.; Chin, J.; Swanson, G.; Canby-Hagino, E.; Crawford, E.D

    2008-01-15

    Context - Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown. Objective - To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 NO MO prostate cancer. Design, Setting, and Patients - Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy. Intervention - Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211). Main Outcome Measures - Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications. Results - Among the 425 men, median follow-up was 10.6 years (inter-quartile range, 9.2-12.7 years). For metastasis-free survival,76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% Cl, 0.58-1.09; P =.16). PSA relapse (median PSA relapse-free survival

  19. SHORT-TIME ANALYSIS FOR ADJUVANT CHEMOTHERAPY IN PATIENTS WITH EARLY-STAGE BULKY CERVICAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    令狐华; 徐小蓉; 梅耀宇; 唐均英; 唐良萏; 孙彤

    2003-01-01

    Objective: To investigate the effect of adjuvant chemotherapy on early stage cervical cancer with bulky tumor. Methods: Between Mar 1998 and Aug 2002, 162 patients of cervical cancer with Ib~IIa stage were investigated. 21 patients with bulky tumors (≥4cm) were managed by cisplatin-based chemotherapy followed by radical hysterectomy and pelvic lymphadenectomy (Bulky-chemo group, BC group). The change of tumor size, the depth of stromal invasion, lymph node metastasis and the involvement of surgical specimens were assessed after operation and compared with those in 57 patients with bulky tumors (Bulky-nonchemo group, BN group) and 84 patients with the tumor size less than 4cm (small group, S group) who underwent surgery as the first step of treatment. Chemotherapy with the same regimen was offered for another 1~2 cycles after operation and the survival situation was followed up. Results: The tumor size of 21 patients in BC group were decreased to varying degrees after chemotherapy, 15 patients were shown as clinical effectiveness (71.43%). And the blood loss during operation (352.35(19.01ml) was significantly lower than that in BN group (619.05(35.58ml), t=4.37) and that in S group (568.07(45.23ml, t=3.36) patients. The incidence of lymph node metastasis (9/78) in patients with bulky tumors was greatly higher than those with tumor size less than 4cm (3/84, X2=4.416); its prevalence rate of deep wall infiltration (8/78) was also higher than that of the latter group (2/84), while with no statistical significance (X2=3.089). Histology showed that there was no case of marginal involvement in all patients. The ratio of both deep stromal invasion (1/21) and positive lymph node (2/21) in BC group was lower than that in BN group (7/57, 7/57 respectively), but neither with statistical significance (X2=0.0103 and 0.8193 respectively). Conclusion: Pre-operative chemotherapy can improve decreasing the primary tumor size and facilitate the following radical surgery. While

  20. Adjuvant role of Pseudomonas flagellin for Acinetobacter baumannii biofilm associated protein

    Science.gov (United States)

    Sefidi, Mozhgan Derakhshan; Rasooli, Iraj; Owlia, Parviz; Talei, Daryush; Astaneh, Shakiba Darvish Alipour; Nazarian, Shahram

    2016-01-01

    AIM To study immunogenicity of Pseudomonas N terminal flagellin as an adjuvant for Acinetobacter baumannii (A. baumannii) biofilm associated protein (Bap). METHODS The N terminal flagellin gene was amplified. The pET28a (+) and polymerase chain reaction products were digested with HindIII and EcoR I. The ligation of N terminal flagellin into pET28a (‏+) was performed using T4 DNA ligase and was then transformed into Escherichia coli BL21 (DE3) as a suitable expression host. pET28a (‏+) vector harboring a conserved region of Bap from our previous work was used. The recombinant proteins were expressed, analyzed by SDS-PAGE method and was purified by affinity chromatography with His-Tag residues followed by confirmation with western blotting. Mice were immunized with recombinant N terminal flagellin and Bap subunits. The immunized animals were intranasally (i.n) challenged with A. baumannii and Pseudomonas aeruginosa (P. aeruginosa). RESULTS The flagellin enhanced the immunogenicity of Bap causing an increase in specific IgG titers in serum (P Bap-Flagellin immunized group challenged with A. baumannii showed significantly lower bacterial load compared to the control group. The bacterial loads were studied in internal organs. A. baumannii infected immunized animals with Bap-Flagellin exhibited internal organs with minor bacterial load while P. aeruginosa PAO1 infected group showed heavy bacterial load of (4.3 ± 0.12) × 106, (1.1 ± 0.01) × 106 and (2.2 ± 0.22) × 106 per gram of lungs, liver and spleen respectively. Bacterial loads were detected per gram of lungs, liver and spleen of the mice group immunized with Bap were (1.2 ± 0.06) × 107, (11.1 ± 0.041) × 105 and (3.6 ± 0.42) × 106 respectively. In vivo neutralization assay indicated that all experimental mice groups, except for Flagellin administered group was significantly (P < 0.05) protected against A. baumannii. CONCLUSION These results demonstrate that P. aeruginosa Flagellin as an adjuvant for

  1. Levamisole as an adjuvant to hepatitis B vaccination in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Mohammad-Hossein Somi

    2015-06-01

    Full Text Available Introduction: High risk of blood-borne infections is one of the problems of patients with chronic kidney disease (CKD, above which, there is hepatitis B. One of the ways to prevent this disease is vaccination against hepatitis B besides observing standard precautions. Lack of response to vaccine in uremic patients has been reported up to 33.0%. The aim of this study was to investigate the effect of levamisole as an adjuvant in improving vaccination response in patients suffering from CKD. Methods: In this cohort study, 30 patients suffering from the chronic renal disease who had undergone levamisole plus hepatitis B vaccine were included in the study as exposed group (Group A. Then 30 equivalent patients who had just underwent hepatitis B vaccination were in the study as a unexposed group (Group B. Antibody titer against hepatitis B virus (HBV was compared between two groups monthly, then data was analyzed. Results: Mean age of all investigated patients was 58.1 ± 14.9 years old, and it ranged from 26 to 82. 23 patients (38.3% were female, and 37 patients (61.7% were male. None of the patients in both groups had a history of previous hepatitis B vaccination. Mean antibody titer was higher in group A than that of the group B after the first and second stages of hepatitis B vaccination. However, the difference between two groups was not statistically significant (P = 0.14 and P = 0.46 respectively. Also, the mean antibody titer after the third stage was 98.8 ± 61 u/l in group A and 86.2 ± 49 u/l in group B where the difference between two groups was not statistically significant (P = 0.38. Side effects resulted from levamisole was not observed in any of patients in group A. Conclusion: According to the results it is possible to express that levamisole pill could be used as a proper adjuvant in improving the response of hepatitis B vaccination in patients suffering from CKD. However, further studies in this field are recommended according to the

  2. Optimization, Production, and Characterization of a CpG-Oligonucleotide-Ficoll Conjugate Nanoparticle Adjuvant for Enhanced Immunogenicity of Anthrax Protective Antigen.

    Science.gov (United States)

    Milley, Bob; Kiwan, Radwan; Ott, Gary S; Calacsan, Carlo; Kachura, Melissa; Campbell, John D; Kanzler, Holger; Coffman, Robert L

    2016-05-18

    We have synthesized and characterized a novel phosphorothioate CpG oligodeoxynucleotide (CpG ODN)-Ficoll conjugated nanoparticulate adjuvant, termed DV230-Ficoll. This adjuvant was constructed from an amine-functionalized-Ficoll, a heterobifunctional linker (succinimidyl-[(N-maleimidopropionamido)-hexaethylene glycol] ester) and the CpG-ODN DV230. Herein, we describe the evaluation of the purity and reactivity of linkers of different lengths for CpG-ODN-Ficoll conjugation, optimization of linker coupling, and conjugation of thiol-functionalized CpG to maleimide-functionalized Ficoll and process scale-up. Physicochemical characterization of independently produced lots of DV230-Ficoll reveal a bioconjugate with a particle size of approximately 50 nm and covalent attachment of more than 100 molecules of CpG per Ficoll. Solutions of purified DV230-Ficoll were stable for at least 12 months at frozen and refrigerated temperatures and stability was further enhanced in lyophilized form. Compared to nonconjugated monomeric DV230, the DV230-Ficoll conjugate demonstrated improved in vitro potency for induction of IFN-α from human peripheral blood mononuclear cells and induced higher titer neutralizing antibody responses against coadministered anthrax recombinant protective antigen in mice. The processes described here establish a reproducible and robust process for the synthesis of a novel, size-controlled, and stable CpG-ODN nanoparticle adjuvant suitable for manufacture and use in vaccines. PMID:27074387

  3. IFN-α as an Adjuvant for Adenovirus-Vectored FMDV Subunit Vaccine through Improving the Generation of T Follicular Helper Cells.

    Directory of Open Access Journals (Sweden)

    Chunxia Su

    Full Text Available IFN-α exhibits either direct antiviral effects or distinct immunomodulatory properties, which was identified as a 'natural immune adjuvant' for both the innate and the adaptive immune responses. Here we have investigated the effects of IFN-α as an adjuvant on the generation of T follicular helper (Tfh cells and antigen-specific antibody responses. The data showed that adenoviral vectors co-expressing FMDV VP1 proteins and porcine IFN-α potently enhanced the generation of Tfh cells, the secretion of IL-21 protein and the expression of Bcl-6 mRNA, compared with adenoviral vectors sole expressing VP1 alone. Additionally, IFN-α substantial increased the number of germinal-center (GC B cells and formation of GCs. Furthermore, IFN-α enhanced the antibody response, as shown by increased production of all IgG and subclasses of IgG1 and IgG2a. Thus, our results revealed the potent adjuvant activity of IFN-α which enhanced the generation of Tfh cells and regulated the humoral immunity by promoting germinal-center reactions and antibody responses.

  4. Long-term persistence of systemic and mucosal immune response to HPV-16/18 AS04-adjuvanted vaccine in preteen/adolescent girls and young women

    DEFF Research Database (Denmark)

    Petäjä, T; Pedersen, C; Andersen, Anne Poder;

    2010-01-01

    Vaccination against oncogenic human papillomavirus (HPV) types is one key intervention for cervical cancer prevention. This follow-up study assessed the persistence of the systemic and mucosal immune responses together with the safety profile of the HPV-16/18 AS04-adjuvanted vaccine administered...... seropositive for serum anti-HPV-16 and -18 antibodies. As previously observed, anti-HPV-16 and -18 antibody levels (ELISA Units/mL) were higher in subjects vaccinated at the age of 10-14 years (2862.2 and 940.8) compared to subjects vaccinated at the age of 15-25 years (1186.2 and 469.8). Moreover, anti-HPV-16...... of transudation or exudation of serum IgG antibodies through the cervical epithelium. The HPV-16/18 AS04-adjuvanted vaccine had a clinically acceptable safety profile. In conclusion, this follow-up study shows that the HPV-16/18 AS04-adjuvanted vaccine administered to preteen/adolescents girls and young women...

  5. Long-term persistence of systemic and mucosal immune response to HPV-16/18 AS04-adjuvanted vaccine in preteen/adolescent girls and young women

    DEFF Research Database (Denmark)

    Petäjä, T; Pedersen, Court; Poder, A;

    2011-01-01

    Vaccination against oncogenic human papillomavirus (HPV) types is one key intervention for cervical cancer prevention. This follow-up study assessed the persistence of the systemic and mucosal immune responses together with the safety profile of the HPV-16/18 AS04-adjuvanted vaccine administered...... seropositive for serum anti-HPV-16 and -18 antibodies. As previously observed, anti-HPV-16 and -18 antibody levels (ELISA Units/mL) were higher in subjects vaccinated at the age of 10-14 years (2862.2 and 940.8) compared to subjects vaccinated at the age of 15-25 years (1186.2 and 469.8). Moreover, anti-HPV-16...... of transudation or exudation of serum IgG antibodies through the cervical epithelium. The HPV-16/18 AS04-adjuvanted vaccine had a clinically acceptable safety profile. In conclusion, this follow-up study shows that the HPV-16/18 AS04-adjuvanted vaccine administered to preteen/adolescents girls and young women...

  6. Effect of folic acid adjuvant therapy on Hcy as well as lipid metabolism and endothelial injury in coronary heart disease patients with stable angina pectoris

    Institute of Scientific and Technical Information of China (English)

    Liang Wen; Yi Xie; Xian-Jun Wu; Rui-Feng Wang; Jian Cao

    2016-01-01

    Objective:To analyze the effect of folic acid adjuvant therapy on Hcy as well as lipid metabolism and endothelial injury in coronary heart disease patients with stable angina pectoris. Methods:A total of 98 cases of coronary heart disease patients with stable angina pectoris who received treatment in our hospital from March 2014 to August 2015 were selected as research subjects and randomly divided into observation group 49 cases and control group 49 cases. Control group received conventional clinical treatment, observation group received folic acid adjuvant therapy, and then differences in levels of Hcy, lipid metabolism, endothelial injury and adhesion molecules were compared between two groups after treatment. Results:Hcy, TC, LDL-C and ApoB values of observation group were lower than those of control group while HDL-C and ApoA1/ApoB values were higher than those of control group;Flow-vel and FMD values of observation group after treatment were higher than those of control group;serum E-selectin, ICAM-1, VCAM-1 and sICAM-1 values of observation group after treatment were lower than those of control group. Conclusion:Folic acid adjuvant therapy for coronary heart disease patients with stable angina pectoris can reduce plasma Hcy level and optimize lipid metabolism, further protects vascular endothelium, and has positive clinical significance.

  7. Design of a shear-thinning recoverable peptide hydrogel from native sequences and application for influenza H1N1 vaccine adjuvant

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Hongzhou; Shi, Jishu; Laskin, Julia; Liu, Ziyan; McVey, David S.; Sun, Xiuzhi S.

    2011-10-07

    Peptide hydrogels are considered injectable materials for drug delivery and tissue engineering applications. Most published hydrogel-forming sequences contain either alternating-charged and noncharged residues or amphiphilic blocks. Here, we report a self-assembling peptide, h9e (FLIVIGSIIGPGGDGPGGD), designed by rationally combining two native sequences from an elastic segment of spider silk and a trans-membrane segment of human muscle L-type calcium channel. The turning segment GSII of h9e promoted hydrogel formation in both Ca2+ solution and acidic pH conditions at water content greater than 99.5%. Although h9e Ca2+ hydrogel and h9e acidic hydrogel have the same sequence, they have distinct physical properties. The shear-thinning, rapid-strengthrecovering h9e Ca2+ hydrogel was used as an H1N1 influenza vaccine adjuvant. The h9e adjuvant was biologically safe and improved immune response by 70% compared with an oil-based commercial adjuvant.

  8. A CpG-Ficoll Nanoparticle Adjuvant for Anthrax Protective Antigen Enhances Immunogenicity and Provides Single-Immunization Protection against Inhaled Anthrax in Monkeys.

    Science.gov (United States)

    Kachura, Melissa A; Hickle, Colin; Kell, Sariah A; Sathe, Atul; Calacsan, Carlo; Kiwan, Radwan; Hall, Brian; Milley, Robert; Ott, Gary; Coffman, Robert L; Kanzler, Holger; Campbell, John D

    2016-01-01

    Nanoparticulate delivery systems for vaccine adjuvants, designed to enhance targeting of secondary lymphoid organs and activation of APCs, have shown substantial promise for enhanced immunopotentiation. We investigated the adjuvant activity of synthetic oligonucleotides containing CpG-rich motifs linked to the sucrose polymer Ficoll, forming soluble 50-nm particles (DV230-Ficoll), each containing >100 molecules of the TLR9 ligand, DV230. DV230-Ficoll was evaluated as an adjuvant for a candidate vaccine for anthrax using recombinant protective Ag (rPA) from Bacillus anthracis. A single immunization with rPA plus DV230-Ficoll induced 10-fold higher titers of toxin-neutralizing Abs in cynomolgus monkeys at 2 wk compared with animals immunized with equivalent amounts of monomeric DV230. Monkeys immunized either once or twice with rPA plus DV230-Ficoll were completely protected from challenge with 200 LD50 aerosolized anthrax spores. In mice, DV230-Ficoll was more potent than DV230 for the induction of innate immune responses at the injection site and draining lymph nodes. DV230-Ficoll was preferentially colocalized with rPA in key APC populations and induced greater maturation marker expression (CD69 and CD86) on these cells and stronger germinal center B and T cell responses, relative to DV230. DV230-Ficoll was also preferentially retained at the injection site and draining lymph nodes and produced fewer systemic inflammatory responses. These findings support the development of DV230-Ficoll as an adjuvant platform, particularly for vaccines such as for anthrax, for which rapid induction of protective immunity and memory with a single injection is very important. PMID:26608924

  9. A novel non-mineral oil-based adjuvant. II. Efficacy of a synthetic sulfolipopolysaccharide in a squalane-in-water emulsion in pigs.

    Science.gov (United States)

    Hilgers, L A; Platenburg, P L; Luitjens, A; Groenveld, B; Dazelle, T; Weststrate, M W

    1994-05-01

    The 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 inactivated influenza virus (iFlu3 containing strains A/Swine, MRC-11 and X-79), inactivated pseudorabies virus (iPRV), live pseudorabies virus (PRV) or inactivated porcine parvovirus (iPPV) as antigen and SLP/S/W or O/W as adjuvant. Antibody titres in serum 2 or 3 weeks after the second immunization were measured by haemagglutination inhibition (HI) or serum neutralization (SN) assays. Both adjuvants significantly augmented the antibody responses against the antigens tested. Mean factors of increase obtained by SLP/S/W and O/W were: 315 and 91, respectively, for A/Swine; 478 and 137 for MRC-11; 362 and 128 for X-79; 69 and 49 for iPRV; and 23 and 7 for live PRV. Increased humoral immunity against live PRV was affirmed by reduced levels and duration of virus excreted by pigs after challenge with virulent PRV. Immunization of pigs with iPPV plus adjuvant SLP/S/W gave 36-fold higher titres than with O/W. It was concluded that SLP/S/W is more effective than O/W in stimulating humoral immunity against the viral antigens examined and that the two constituents SLP and S/W interact synergistically. Advantages of SLP/S/W over O/W include stronger adjuvanticity, better biocompatibility and lower doses of active substances.

  10. Adjuvant effects of sulfolipo-cyclodextrin in a squalane-in-water and water-in-mineral oil emulsions for BHV-1 vaccines in cattle.

    Science.gov (United States)

    Romera, S A; Hilgers, L A; Puntel, M; Zamorano, P I; Alcon, V L; Dus Santos, M J; Blanco Viera, J; Borca, M V; Sadir, A M

    2000-08-15

    The antibody and cell mediated immune responses induced by BHV-1 were analysed in cattle after vaccination and challenge exposure to the virulent strain LA of BHV-1. Animals were vaccinated intramuscularly (IM) with inactivated virus vaccines against BHV-1 containing either a water in mineral oil adjuvant (W/O), a water in mineral oil adjuvant plus Avridine (W/O+Avridine) or sulfolipo-cyclodextrin in squalane in-water emulsion (SL-CD/S/W). No significant differences were registered in the antibody response induced by the three evaluated vaccines. However, the BHV-1 specific cell-mediated immunite response was stronger and appeared earlier when SL-CD/S/W was included in the formulation. The efficacy of the vaccines was also evaluated after intranasal challenge of the calves with a virulent BHV-1 LA strain. Animals vaccinated with SL-CD/S/W had reduced virus excretion and clinical symptoms compared with the mock-vaccinated animals. Comparison of levels of BHV-1 specific IgG2 and IgG1 with virus shedding revealed that, regardless of the adjuvant administered, animals showing BHV-1 specific IgG2/IgG1 ratios higher than 1 were those with a significant lower number of individuals shedding virus. Additionally, animals vaccinated with SL-CD/S/W presented no post-vaccinal reactions. These factors, combined with the higher efficacy and the ease of manipulation of the biodegradable oil, makes the vaccine formulated with this new adjuvant an important contribution for the veterinary vaccines industry.

  11. Quantitative and epitope-specific antigenicity analysis of the human papillomavirus 6 capsid protein in aqueous solution or when adsorbed on particulate adjuvants.

    Science.gov (United States)

    Li, Min; Wang, Xin; Cao, Lu; Lin, Zhijie; Wei, Minxi; Fang, Mujin; Li, Shaowei; Zhang, Jun; Xia, Ningshao; Zhao, Qinjian

    2016-08-17

    Human papillomavirus (HPV) 6 is a human pathogen which causes genital warts. Recombinant virus-like particle (VLP) based antigens are the active components in prophylactic vaccines to elicit functional antibodies. The binding and functional characteristics of a panel of 15 murine monoclonal antibodies (mAbs) against HPV6 was quantitatively assessed. Elite conformational indicators, recognizing the conformational epitopes, are also elite viral neutralizers as demonstrated with their viral neutralization efficiency (5 mAbs with neutralization titer below 4ng/mL) in a pseudovirion (PsV)-based system. The functionality of a given mAb is closely related to the nature of the corresponding epitope, rather than the apparent binding affinity to antigen. The epitope-specific antigenicity assays can be used to assess the binding activity of PsV or VLP preparations to neutralizing mAbs. These mAb-based assays can be used for process monitoring and for product release and characterization to confirm the existence of functional epitopes in purified antigen preparations. Due to the particulate nature of the alum adjuvants, the vaccine antigen adsorbed on adjuvants was considered largely as "a black box" due to the difficulty in analysis and visualization. Here, a novel method with fluorescence-based high content imaging for visualization and quantitating the immunoreactivity of adjuvant-adsorbed VLPs with neutralizing mAbs was developed, in which antigen desorption was not needed. The facile and quantitative in situ antigenicity analysis was amendable for automation. The integrity of a given epitope or two non-overlapping epitopes on the recombinant VLPs in their adjuvanted form can be assessed in a quantitative manner for cross-lot or cross-product comparative analysis with minimal manipulation of samples. PMID:27426626

  12. A CpG-Ficoll Nanoparticle Adjuvant for Anthrax Protective Antigen Enhances Immunogenicity and Provides Single-Immunization Protection against Inhaled Anthrax in Monkeys.

    Science.gov (United States)

    Kachura, Melissa A; Hickle, Colin; Kell, Sariah A; Sathe, Atul; Calacsan, Carlo; Kiwan, Radwan; Hall, Brian; Milley, Robert; Ott, Gary; Coffman, Robert L; Kanzler, Holger; Campbell, John D

    2016-01-01

    Nanoparticulate delivery systems for vaccine adjuvants, designed to enhance targeting of secondary lymphoid organs and activation of APCs, have shown substantial promise for enhanced immunopotentiation. We investigated the adjuvant activity of synthetic oligonucleotides containing CpG-rich motifs linked to the sucrose polymer Ficoll, forming soluble 50-nm particles (DV230-Ficoll), each containing >100 molecules of the TLR9 ligand, DV230. DV230-Ficoll was evaluated as an adjuvant for a candidate vaccine for anthrax using recombinant protective Ag (rPA) from Bacillus anthracis. A single immunization with rPA plus DV230-Ficoll induced 10-fold higher titers of toxin-neutralizing Abs in cynomolgus monkeys at 2 wk compared with animals immunized with equivalent amounts of monomeric DV230. Monkeys immunized either once or twice with rPA plus DV230-Ficoll were completely protected from challenge with 200 LD50 aerosolized anthrax spores. In mice, DV230-Ficoll was more potent than DV230 for the induction of innate immune responses at the injection site and draining lymph nodes. DV230-Ficoll was preferentially colocalized with rPA in key APC populations and induced greater maturation marker expression (CD69 and CD86) on these cells and stronger germinal center B and T cell responses, relative to DV230. DV230-Ficoll was also preferentially retained at the injection site and draining lymph nodes and produced fewer systemic inflammatory responses. These findings support the development of DV230-Ficoll as an adjuvant platform, particularly for vaccines such as for anthrax, for which rapid induction of protective immunity and memory with a single injection is very important.

  13. Tamoxifen with ovarian function suppression versus tamoxifen alone as an adjuvant treatment for premenopausal breast cancer: a meta-analysis of published randomized controlled trials

    Science.gov (United States)

    Yan, Shunchao; Li, Kai; Jiao, Xin; Zou, Huawei

    2015-01-01

    Background Ovarian function suppression (OFS) significantly downregulates the concentration of plasma estrogens. However, it is unclear whether it offers any survival benefits if combined with adjuvant tamoxifen treatment in premenopausal women. This meta-analysis was designed to assess data from previous studies involving adjuvant tamoxifen treatment plus OFS in premenopausal breast cancer. Methods Electronic literature databases (PubMed, Embase, the Web of Science, and the Cochrane Library) were searched for relevant randomized controlled trials published prior to February 1, 2015. Only randomized controlled trials that compared tamoxifen alone with tamoxifen plus OFS for premenopausal women with breast cancer were selected. The evaluated endpoints were disease-free survival and overall survival. Results Four randomized controlled trials comprising 6,279 patients (OFS combination, n=3,133; tamoxifen alone, n=3,146) were included in the meta-analysis. There was no significant improvement in disease-free survival or overall survival with addition of OFS in either the whole population or the hormone receptor-positive subgroup. The risk of distant recurrence was not reduced with the addition of OFS in the whole population. A subgroup analysis showed that addition of OFS significantly improved overall survival in patients who were administered chemotherapy. Conclusion Based on the available studies, concurrent administration of OFS and adjuvant tamoxifen treatment for premenopausal women with breast cancer has no effect on prolonging disease-free survival and overall survival, excluding patients who were administered chemotherapy. It should not be widely recommended, except perhaps for women who were hormone-receptor positive and who were also administered adjuvant chemotherapy. PMID:26109867

  14. Evaluating the efficacy of rBmHATαc as a multivalent vaccine against lymphatic filariasis in experimental animals and optimizing the adjuvant formulation

    Science.gov (United States)

    Dakshinamoorthy, Gajalakshmi; Kalyanasundaram, Ramaswamy

    2013-01-01

    Developing an effective vaccine against lymphatic filariasis will complement the WHO's effort to eradicate the infection from endemic areas. Currently 83 different countries are endemic for this infection and over 1 billion people are at risk. An effective vaccine coupled with mass drug administration will reduce the morbidity and social stigma associated with this gruesome disease. Several potential vaccine candidates that can confer partial protection in experimental animals have been reported from different laboratories. However, no licensed vaccines are currently available for this disease. Among the several vaccine antigens identified from our laboratory, three most promising antigens; rBmHSPαc (α crystalline domain and c-terminal extension of Heat Shock Protein 12.6), rBmALT-2 (Abundant larval transcript) and rBmTSP LEL (Tetraspanin large extracellular loop) was further developed as a recombinant fusion protein vaccine (rBmHATαc). In a mouse model this fusion protein vaccine gave close to 68% protection following a challenge infection. To improve the vaccine efficiency of rBmHATαc, in this study we evaluated various preparations of alum (AL007, AL019, Alhydrogel and Imject® Alum) as adjuvants. Our results show that mice immunized with rBmHATαc formulated in AL007 (alum from IDRI) and/or AL019 (alum plus TLR-4 agonist from IDRI) gave the highest IgG antibody titer compared to other groups. Subsequent in vivo challenge experiments confirmed that >95% protection can be achieved when AL007 or AL019 was used as the adjuvant. However, when Imject® Alum or alhydrogel was used as the adjuvant only 76% and 72% protection respectively could be achieved. These results show that AL007 or AL019 (IDRI) is an excellent choice of adjuvant for the rBmHATαc vaccine against B. malayi L3 in mice. PMID:24211167

  15. The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice.

    Directory of Open Access Journals (Sweden)

    Jessica A Hess

    2016-07-01

    Full Text Available In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses.Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2.The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans.

  16. Adjuvant chemotherapy, a valuable alternative option in selected patients with cervical cancer.

    Directory of Open Access Journals (Sweden)

    Shuang Li

    Full Text Available Radiotherapy is the standard treatment for cervical cancer, but causes radiotherapy-induced complications. Recently, chemotherapy has been more extensively utilized. Here, we perform a large-scale comparison of chemotherapy and radiotherapy. From 2002 to 2008, 2,268 patients were grouped according to adjuvant radiotherapy or chemotherapy before and/or after surgery, and we compared the 5-year overall survival (OS and disease-free survival (DFS rates, recurrence rates, side effects, quality of life (QoL, and sexual activity. There were no significant differences between the treatment groups for the 5-year OS and DFS rates (OS: p = 0.053, DFS: p = 0.095, although marginally improved outcomes were observed in the chemotherapy group (OS: 86.5% vs. 82.8%; DFS: 84.5% vs. 81.4%. However, patients with early-stage disease, clinical response, and younger age had increased 5-year OS and DFS rates following chemotherapy compared to radiotherapy (p<0.05. The chemotherapy group exhibited significantly lower 5-year recurrence and distant failure rates compared to the radiotherapy group (p<0.001 and p = 0.007, respectively. Nausea and vomiting were the most frequent short-term complications of chemotherapy, whereas bowel and urinary complications were more frequent in the radiotherapy group. Compared to the chemotherapy group, patients who received radiotherapy reported a lower QoL, less frequent sexual activity, and more severe menopausal symptoms (p<0.05. Cervical cancer patients treated with chemotherapy, especially those with early-stage disease, clinical responses, and younger ages, have more positive outcomes, fewer complications, better QoL and sexual activity, suggesting that chemotherapy may be a valuable alternative option for selected patients.

  17. Adjuvant effect of liposome in chicken result from induction of nitric oxide

    International Nuclear Information System (INIS)

    Intranasal delivery of liposome-encapsulated inactivated Newcastle Disease virus (NDV) is known to be an effective vaccine for inducing immunity in the respiratory tract from our previous reports. Four-week-old specific pathogen-free chickens were intranasally immunized with NDV entrapped in phosphatidylcholine-liposomes (PC-Lip). The mucosal levels of anti-NDV s-immunoglobulin A (IgA), serum IgG, a high hemagglutination inhibition titer (1:640), and the high survival rate with the PC-Lip vaccine were comparable to those of our previous report. The immune mechanisms of the PC-Lip adjuvant were determined by in vitro cellular experiments using the NO production of chicken spleen macrophages. The most important finding of this study was proving that macrophages were stimulated by PC-Lip via the extracellular regulated kinase (ERK) 1/2 and nuclear factor (NF)-κB activation pathways. This finding may be useful for developing potent mucosal vaccine delivery systems in the future.

  18. Weight gain during adjuvant endocrine treatment for early-stage breast cancer: What is the evidence?

    Science.gov (United States)

    Nyrop, K A; Williams, G R; Muss, H B; Shachar, S S

    2016-07-01

    Most breast cancer (BC) tumors are early stage and hormone receptor positive, where treatment generally includes adjuvant endocrine treatment (ET). Oncology providers and women about to start ET want to know about side effects, including potential weight gain. The aim of this study was a literature review to identify the independent effect of ET on post-diagnosis weight gain. Weight gain is of concern with regard to potential associations with BC recurrence, mortality, and quality of life in survivorship. We conducted a targeted review of the literature. Thirty-eight studies met our inclusion criteria. Patient-reported weight gain ranged widely from 18 to 52 % of patients in Year 1 and from 7 to 55 % in Year 5. Some studies reported categories of weight change: lost weight (9-17 %), stable weight (47-64 %), and gained weight (27-36 %). Most studies comparing ET with placebo or tamoxifen with AI reported no significant difference between the two groups. Wide-ranging and inconsistent results point to the need for further research to clarify annual weight change (loss, gain, stability) from BC diagnosis through 5 years of ET and beyond. There is also a need to explore weight change by type of ET and to explore risk factors for weight gain in women on ET, including tumor type, sociodemographic characteristics, and health behaviors. More specific information is needed to identify high-risk BC patients who could be targeted for weight management interventions. PMID:27342454

  19. Calreticulin as cancer treatment adjuvant: combination with photodynamic therapy and photodynamic therapy-generated vaccines

    Directory of Open Access Journals (Sweden)

    Mladen eKorbelik

    2015-02-01

    Full Text Available Calreticulin is recognized as one of pivotal damage-associated molecular pattern (DAMP molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT. The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure-rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4 mg/mouse was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor responses elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities.

  20. Interleukin-12 as a Genetic Adjuvant Enhances Hepatitis C Virus NS3 DNA Vaccine Immunogenicity

    Institute of Scientific and Technical Information of China (English)

    Malihe Naderi; Atefeh Saeedi; Abdolvahab Moradi; Mishar Kleshadi; Mohammad Reza Zolfaghari; Ali Gorji; Amir Ghaemi

    2013-01-01

    Hepatitis C virus (HCV) chronic infection is a worldwide health problem,and numerous efforts have been invested to develop novel vaccines.An efficient vaccine requires broad immune response induction against viral proteins.To achieve this goal,we constructed a DNA vaccine expressing nonstructural 3 (NS3) gene (pcDNA3.1-HCV-NS3) and assessed the immune response in C57BL/6 mice.In this study,the NS3 gene was amplified with a nested-reverse transcriptase-polymerase chain reaction (RT-PCR) method using sera of HCV-infected patients with genotype 1 a.The resulting NS3 gene was subcloned into a pcDNA3.1 eukaryotic expression vector,and gene expression was detected by western blot.The resultant DNA vaccine was co-administered with interleukin-12 (IL-12) as an adjuvant to female C57BL/6 mice.After the final immunizations,lymphocyte proliferation,cytotoxicity,and cytokine levels were assessed to measure immune responses.Our data suggest that co-administration of HCV NS3 DNA vaccine with IL-12 induces production of significant levels of both IL-4 and interferon (IFN)-γ (p<0.05).Cytotoxicity and lymphocyte proliferation responses of vaccinated mice were significantly increased compared to control (p<0.05).Collectively,our results demonstrated that co-administration of HCV NS3 and IL-12 displayed strong immunogenicity in a murine model.

  1. Molecular Adjuvant Ag85A Enhances Protection against Influenza A Virus in Mice Following DNA Vaccination

    Directory of Open Access Journals (Sweden)

    Hong Li

    2012-12-01

    Full Text Available A novel DNA vaccine vector encoding the Mycobacterium tuberculosis secreted antigen Ag85A fused with the influenza A virus (IAV HA2 protein epitopes, pEGFP/Ag85A-sHA2 (pAg85A-sHA2, was designed to provide protection against influenza. The antigen encoded by the DNA vaccine vector was efficiently expressed in mammalian cells, as determined by reverse transcription polymerase chain reaction (RT-PCR and fluorescence analyses. Mice were immunized with the vaccine vector by intramuscular injection before challenge with A/Puerto Rico/8/34 virus (PR8 virus. Sera and the splenocyte culture IFN-γ levels were significantly higher in immunized mice compared with the control mice. The novel vaccine group showed a high neutralization antibody titer in vitro. The novel vaccine vector also reduced the viral loads, increased the survival rates in mice after the PR8 virus challenge and reduced the alveolar inflammatory cell numbers. Sera IL-4 concentrations were significantly increased in mice immunized with the novel vaccine vector on Day 12 after challenge with the PR8 virus. These results demonstrated that short HA2 (sHA2 protein epitopes may provide protection against the PR8 virus and that Ag85A could strengthen the immune response to HA2 epitopes, thus, Ag85A may be developed as a new adjuvant for influenza vaccines.

  2. Latent Membrane Protein 1 as a molecular adjuvant for single-cycle lentiviral vaccines

    Directory of Open Access Journals (Sweden)

    Rahmberg Andrew R

    2011-05-01

    Full Text Available Abstract Background Molecular adjuvants are a promising method to enhance virus-specific immune responses and protect against HIV-1 infection. Immune activation by ligands for receptors such as CD40 can induce dendritic cell activation and maturation. Here we explore the incorporation of two CD40 mimics, Epstein Barr Virus gene LMP1 or an LMP1-CD40 chimera, into a strain of SIV that was engineered to be limited to a single cycle of infection. Results Full length LMP1 or the chimeric protein LMP1-CD40 was cloned into the nef-locus of single-cycle SIV. Human and Macaque monocyte derived macrophages and DC were infected with these viruses. Infected cells were analyzed for activation surface markers by flow cytometry. Cells were also analyzed for secretion of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-12p70 and TNF by cytometric bead array. Conclusions Overall, single-cycle SIV expressing LMP1 and LMP1-CD40 produced a broad and potent TH1-biased immune response in human as well as rhesus macaque macrophages and DC when compared with control virus. Single-cycle SIV-LMP1 also enhanced antigen presentation by lentiviral vector vaccines, suggesting that LMP1-mediated immune activation may enhance lentiviral vector vaccines against HIV-1.

  3. Evaluation of Placental Extracts as an Adjuvant Therapy to Phenol in Treatment of Idiopathic Guttate Hypomelanosis

    Science.gov (United States)

    Tripathi, Swati; Kaur, Manjinder

    2016-01-01

    Introduction Idiopathic Guttate Hypomelanosis (IGH) macules are hypo pigmented lesions occurring due to decreased functioning of melanocytes due to photosensitivity or persistent irritation of skin in middle aged and elderly. Aim To find out the efficacy of placental extracts when used as an adjunct with 88% phenol for the treatment of IGH macules. Materials and Methods A total of 40 patients were randomly divided into two groups (n=20 in each group), viz group P, (the control group, treated with only 88% phenol) and Group PP (study group, treated with Placental extracts along with 88% phenol). Spot peeling was done with 88% phenol in both the groups while group PP was advised to use placental extract at night for 3 months. Patients of both groups were assessed both subjectively and objectively after every session and at the end of 3 months of initiation of therapy. The statistical analysis was done using Chi-square test, Z-test and a p-value<0.05 was considered significant. Results Both the groups showed significant re-pigmentation of lesions i.e., 76.8% in group P and 79.1% in group PP; whereas, what group PP had shown was non- significantly (p=0.8203) better as compared to group P. Conclusion The clinical and patient acceptability of phenol along with the placental extracts as an adjuvant was better with similar results. Hence, the use of placental extract is recommended along with phenol in IGH lesions. PMID:27656538

  4. Psychoneuroimmunology-Based Stress Management during Adjuvant Chemotherapy for Early Breast Cancer.

    Science.gov (United States)

    Robins, Jo Lynne W; McCain, Nancy L; Elswick, R K; Walter, Jeanne M; Gray, D Patricia; Tuck, Inez

    2013-01-01

    Objective. In a randomized trial of women with early stage breast cancer undergoing adjuvant chemotherapy, two stress management interventions, tai chi training and spiritual growth groups, were compared to a usual care control group, to evaluate psychosocial functioning, quality of life (QOL), and biological markers thought to reflect cancer- and treatment-specific mechanisms. Method. The sample consisted of 145 women aged 27-75 years; 75% were Caucasian and 25% African American. A total of 109 participants completed the study, yielding a 75% retention rate. Grounded in a psychoneuroimmunology framework, the overarching hypothesis was that both interventions would reduce perceived stress, enhance QOL and psychosocial functioning, normalize levels of stress-related neuroendocrine mediators, and attenuate immunosuppression. Results. While interesting patterns were seen across the sample and over time, the interventions had no appreciable effects when delivered during the period of chemotherapy. Conclusions. Findings highlight the complex nature of biobehavioral interventions in relation to treatment trajectories and potential outcomes. Psychosocial interventions like these may lack sufficient power to overcome the psychosocial or physiological stress experienced during the chemotherapy treatment period. It may be that interventions requiring less activity and/or group attendance would have enhanced therapeutic effects, and more active interventions need to be tested prior to and following recovery from chemotherapy.

  5. Psychoneuroimmunology-Based Stress Management during Adjuvant Chemotherapy for Early Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jo Lynne W. Robins

    2013-01-01

    Full Text Available Objective. In a randomized trial of women with early stage breast cancer undergoing adjuvant chemotherapy, two stress management interventions, tai chi training and spiritual growth groups, were compared to a usual care control group, to evaluate psychosocial functioning, quality of life (QOL, and biological markers thought to reflect cancer- and treatment-specific mechanisms. Method. The sample consisted of 145 women aged 27–75 years; 75% were Caucasian and 25% African American. A total of 109 participants completed the study, yielding a 75% retention rate. Grounded in a psychoneuroimmunology framework, the overarching hypothesis was that both interventions would reduce perceived stress, enhance QOL and psychosocial functioning, normalize levels of stress-related neuroendocrine mediators, and attenuate immunosuppression. Results. While interesting patterns were seen across the sample and over time, the interventions had no appreciable effects when delivered during the period of chemotherapy. Conclusions. Findings highlight the complex nature of biobehavioral interventions in relation to treatment trajectories and potential outcomes. Psychosocial interventions like these may lack sufficient power to overcome the psychosocial or physiological stress experienced during the chemotherapy treatment period. It may be that interventions requiring less activity and/or group attendance would have enhanced therapeutic effects, and more active interventions need to be tested prior to and following recovery from chemotherapy.

  6. Adjuvant effect of liposome in chicken result from induction of nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yuh-Feng [Division of Nephrology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (China); Deng, Ming-Chung [Department of Hog Cholera, Animal Health Research Institute, Council of Agriculture, Taipei, Taiwan (China); Tseng, Li-Ping; Jiang, Pei-Rong; Liu, Der-Zen [Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan (China); Jan, Tong-Rong [Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); Hsieh, Fang-I, E-mail: tonyliu@tmu.edu.tw, E-mail: hsiehfangi@tmu.edu.tw [School of Public Health, Taipei Medical University, Taipei, Taiwan (China)

    2011-02-15

    Intranasal delivery of liposome-encapsulated inactivated Newcastle Disease virus (NDV) is known to be an effective vaccine for inducing immunity in the respiratory tract from our previous reports. Four-week-old specific pathogen-free chickens were intranasally immunized with NDV entrapped in phosphatidylcholine-liposomes (PC-Lip). The mucosal levels of anti-NDV s-immunoglobulin A (IgA), serum IgG, a high hemagglutination inhibition titer (1:640), and the high survival rate with the PC-Lip vaccine were comparable to those of our previous report. The immune mechanisms of the PC-Lip adjuvant were determined by in vitro cellular experiments using the NO production of chicken spleen macrophages. The most important finding of this study was proving that macrophages were stimulated by PC-Lip via the extracellular regulated kinase (ERK) 1/2 and nuclear factor (NF)-{kappa}B activation pathways. This finding may be useful for developing potent mucosal vaccine delivery systems in the future.

  7. Experimental investigation of anti-rheumatoid activity of Pleurotus sajorcaju in adjuvant-induced arthritic rats

    Institute of Scientific and Technical Information of China (English)

    Patel Pinal; Patel Dharmik; Patel Natvarlal

    2012-01-01

    Pleurotus sajorcaju (P.sajorcaju),an edible and non-toxic mushroom,was evaluated as antioxidant,antitumor,anti-inflammatory and antihypertensive activities.P.sajorcaju is a good source of carbohydrates,dietary fiber,essential amino acids,minerals,vitamin B,folic acid and steroids.Anti-inflammatory,immunomodulatory and analgesic activities of aqueous and methanolic extracts of mycelium of P.sajorcaju were investigated (data is not shown).This finding suggests that extracts of P.sajorcaju can be used against inflammatory and autoimmune disease.So,P.sajorcaju examined for its antiarthritic activity.Plant was collected and separately extracted with water and methanol.For antiarthritic activity 500 and 1 000 mg·kg-1 of both extracts were prepared and administered by oral route.Body weight,paw edema (inflammation),hematological parameter,spleen weight,radiological and histological analysis of bone damage were assessed in rats with Freund's adjuvant induced paw inflammation.Both extracts showed significant and dose-dependent anti-inflammatory and anti-arthritic effects compared to control group.

  8. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity

    NARCIS (Netherlands)

    Kreutz, M.; Giquel, B.; Hu, Q.; Abuknesha, R.; Uematsu, S.; Akira, S.; Nestle, F.O.; Diebold, S.S.

    2012-01-01

    Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is par

  9. Comparative effectiveness in esophagogastric cancer.

    Science.gov (United States)

    Knab, Lawrence M; Belotte, Jim; Munshi, Hidayatullah G; Bentrem, David J

    2015-01-01

    Cancer of the esophagus and the gastroesophageal junction (GEJ) continues to have a dismal prognosis, with the incidence of esophageal cancer increasing in the United States. Although radical resection was initially the primary treatment for this disease process, systemic chemotherapy and radiation have been shown to play a role in prolonging survival in most patient populations. This chapter explores the evidence that guides treatment for esophageal and GEJ cancer today. Chemotherapy and radiation therapy were introduced as treatment modalities for esophageal and GEJ cancers when it became evident that surgical therapy alone provided poor long-term survival rates. A variety of treatment strategies have been explored including preoperative (neoadjuvant) and postoperative (adjuvant) chemotherapy, with and without radiation. The evidence suggests that neoadjuvant chemotherapy or chemoradiotherapy provides better outcomes compared to surgery alone for esophageal, GEJ, and gastric cancers. Studies indicate a trend towards improved survival when neoadjuvant chemoradiotherapy is compared to chemotherapy alone. When patients have undergone resection with node-positive disease without receiving neoadjuvant therapy, some form of adjuvant treatment is recommended. This chapter also explores the surgical management of esophageal, GEJ, and gastric cancers including the extent of the gastric lymph node dissection. It also includes a discussion about adherence to national guidelines in terms of gastric cancer treatment and esophageal and gastric lymph node examinations.

  10. Molecular cloning, expression and the adjuvant effects of interleukin-8 of channel catfish (Ictalurus Punctatus) against Streptococcus iniae

    OpenAIRE

    Erlong Wang; Jun Wang; Bo Long; Kaiyu Wang; Yang He; Qian Yang; Defang Chen; Yi Geng; Xiaoli Huang; Ping Ouyang; Weimin Lai

    2016-01-01

    Interleukin-8 (IL-8) as an important cytokine involving in inflammatory and immune response, has been studied as effective adjuvants for vaccines in mammals. However, there are fewer reports about the characterization and adjuvant effects of IL-8 in fish. In this study, cloning and sequence analysis of IL-8 coding region of channel catfish (Ictalurus punctatus) were conducted, mature IL-8(rtIL-8) was expressed and evaluated for its adjuvant effects on the immunoprotection of subunit vaccine e...

  11. Comparison of immunogenicity of Aluminum salts as adjuvant for recombinant Hepatitis-B vaccine

    Directory of Open Access Journals (Sweden)

    Fazeli MR

    2007-05-01

    Full Text Available Background: Aluminum salts are common adjuvants in human and animal vaccine preparations. The two adjuvants aluminum phosphate and aluminum hydroxide show acceptable immunoadjuvant properties with many antigens. These two salts have different physicochemical characteristics that make each one suitable for certain antigens. The surface antigen of Hepatitis B (HBsAg has several antigenic epitopes that bind to aluminum adjuvants by a ligand exchange mechanism. Although HBV vaccines using an aluminum hydroxide adjuvant are available, higher antigenicity is needed for the subgroup of people who do not respond sufficiently to the currently available vaccines. Methods: A solution of recombinant HBsAg for making different formulations of vaccines with aluminum phosphate (Adju-Phos® and aluminum hydroxide (Alhydrogel® adjuvants was obtained from Darupakhsh Pharmaceutical Company. The total protein content, antigenicity, and purity of HBsAg solution were determined using BCA, ELISA, and SDS-PAGE methods, respectively. The different formulations were prepared in the lab and administered i.p. to two test groups of Balb/C mice and a third test group received the Engerix vaccine, which is currently available on the market and uses an aluminum hydroxide adjuvant. The control group of animals received the solution without antigen. After 28 days, heart blood samples were collected and serum was separated to determine the antibody titer against HBsAg using an ELISA kit. Results: This study shows that the vaccine formulated with aluminum phosphate exerted more immunogenicity than both the aluminum hydroxide laboratory formulation and the Engerix vaccines. Conclusion: Although the results of our study indicate higher immunogenic properties of the vaccine formulated with the aluminum phosphate adjuvant, complementary experiments are needed to further evaluate the biological properties with respect to effectiveness, adverse effects, product stability and finally

  12. ADJUVANT CHEMOTHERAPY FOLLOWING RADICAL SURGERY FOR NON-SMALL CELL LUNG CANCER:A RANDOMIZED STUDY

    Institute of Scientific and Technical Information of China (English)

    XU Guang-chuan; RONG Tie-hua; LIN Peng

    1999-01-01

    Objective: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small cell lung cancer (NSCLC). Methods: Seventy patients with NSCLC (stage Ⅰ-Ⅲ) undergone radical surgery were randomized into two groups: 35 patients received adjuvant chemotherapy with cyclophosphamide (CTX)300 mg/m2, vincristine (VCR) 1.4% mg/m2, adriamycin (ADM) 50 mg/m2, lomustine (CCNU) 50 mg/m2 d1,cisplatin (DDP) 20 mg/m2, d1-5, for 4 cycles, and followed by oral Ftorafur (FT-207) 600-900 mg/d for 1year (adjuvant chemotherapy group). The other 35patients received surgical treatment only (surgery group). Results: The overall 5-year survival rate was 48.6% in the adjuvant chemotherapy group, and 31.4%in the surgery group, respectively. The difference between the two groups was not statistically significant (P>0.05). The 5-year survival rate of patients in stage Ⅲwas 44.0% and 20.8% received surgery with and without adjuvant chemotherapy, respectively. The difference between the two groups was statistically significant (P<0.025). The 5-year survival rate of patients in stage Ⅰ-Ⅱ in the two groups was 60.0% and 54.5%, respectively (P>0.75). Conclusion: Postoperative adjuvant chemotherapy in NSCLC can improve survival, for those patients in stage Ⅲ, it suggests significantly 5-year survival rate in the adjuvant chemotherapy group was higher than that in the surgery alone group.

  13. Preparation and evaluation of functional foods in adjuvant arthritis

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    Al-Okbi, S. Y.

    2012-10-01

    Full Text Available 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 functional foods containing such bioactive fractions separately or in combination and to evaluate them in adjuvant arthritis in rats, study the stability of bioactive ingredients and evaluate their sensory properties. The studied biochemical parameters were erythrocyte sedimentation rate, erythrocyte superoxide dismutase, glutathione peroxidase and plasma copper, zinc and interlukin 2. Nutritional parameters, including body weight gain, food intake and food efficiency ratio were monitored during the feeding of the functional foods. The bioactive ingredients assessed were total phenolic contents and fatty acids. The results showed improvement in the biochemical parameters, body weight gain and food efficiency ratio of arthritic rats fed on the functional foods with different degrees. All the prepared functional foods were sensory accepted. The active ingredients showed stability during storage. In conclusion, all the tested functional foods showed promising antiinflammatory activity and were determined to be acceptable through sensory evaluation which means that their potential beneficial use as dietary supplements in rheumatoid arthritis patients may be recommended.

    La artritis adyuvante es un modelo utilizado en animales y se caracteriza por ser muy parecida a la artritis reumatoide en humanos. Se trata de un modelo de trabajo utilizado con éxito para estudiar nuevos agentes anti-inflamatorios. En estudios previos (animales y clínica hemos demostrado que

  14. Neo-adjuvant chemotherapy in advanced hypopharyngeal carcinoma

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    P Joshi

    2013-01-01

    Full Text Available Objective: The aim of this retrospective study was to find out the role of neo-adjuvant chemotherapy (NACT in changing the management and outcome of advanced hypopharyngeal cancer patients. Materials and Methods: This is a retrospective analysis of 59 treatment naïve, advanced hypopharyngeal cancer patients presenting to our tertiary care center from April 2010 to October 2011. NACT was given as two (platinum with taxane or three drug with (platinum, taxane with 5-flurouracil [5 FU] as 3 weekly regimen with cisplatin and docetaxel as 75 mg/m 2 each, 5-FU as 1000 mg/m 2 . NACT was either given with the intent of achieving: (1 surgical resection (extensive soft tissue disease, oropharyngeal involvement, extensive disease with cartilage erosion or (2 organ preservation (Bulky disease with inner cartilage erosion, exolaryngeal disease without cartilage erosion, large N3 nodes. Results: The mean age of this population was 55 years. Most (83% of the patients had pyriform sinus (PFS involvement. 69% patients had Stage IVa disease, 21% Stage IVb and 10% Stage III. The overall response rate was 66%, including 06% complete responses and 60% partial responses. Following NACT, resectability was achieved in 30% (10/33 and organ preservation protocol was planned after NACT in 73% (19/26 patients. The main toxicities were neutropenia (grade 3, 4, 04%; febrile neutropenia, 4%, mucositis 5%, diarrhea 5%. The median progression free survival was 20 months. Conclusions: NACT can be useful in patients with oropharyngeal involvement to achieve surgical resection and larynx preservation in patients with bulky T3 disease.

  15. Is neo-adjuvant chemotherapy a better option for management of cervical cancer patients of rural India?

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    G A Dastidar

    2016-01-01

    Full Text Available Objectives: To explore alternate modality of treatment in patients of advanced cancer cervix by neo-adjuvant chemotherapy (NACT followed by External Beam Radiotherapy (ERT and Brachytherapy (BT. Short- (6 months and long- (12 months term follow-up data from these patients were compared with the retrospective data from an urban cancer centre, where standard protocol of concurrent chemo-radiotherapy is practiced. Materials and Methods: Two hundred patients of advanced cervical cancer, treated at our rural cancer centre between January 2007 and December 2007, were included in the study arm (Group A. These patients received three cycles of neo-adjuvant chemotherapy with Cisplatin, Bleomycin, and Vincristine before External-Beam Radiotherapy (EBT followed by brachytherapy. Patients in the control arm (Group B of an urban cancer centre, received EBT with weekly concomitant Cisplatin, followed by brachytherapy. Short- (6 months and long- (12 months term follow-up data from our patients were compared with the retrospective data from the urban cancer centre. Results and Analysis: Complete response rate was comparatively higher among patients of Group A, also correspondingly proportion of patients showing progressive disease and stable disease was lower among them. Local treatment failure was 87.5% among patients from Group A and 94.4% in Group B patients. Concomitant chemoradiation (CRT was associated with more GI toxicities. Conclusion: Our result suggests NACT arm is as effective as CRT arm in respect of complete response with less pelvic failure and G.I toxicities. Further follow-up data are needed before arriving at a definite conclusion.

  16. Modern Vaccines/Adjuvants Formulation--Session 2 (Plenary II): May 15-17, 2013--Lausanne, Switzerland.

    Science.gov (United States)

    Collin, Nicolas

    2013-09-01

    On the 15-17th May 2013, the Fourth International Conference on Modern Vaccines/Adjuvants Formulation was organized in Lausanne, Switzerland, and gathered stakeholders from academics and from the industry to discuss several challenges, advances and promises in the field of vaccine adjuvants. Plenary session 2 of the meeting was composed of four different presentations covering: (1) the recent set-up of an adjuvant technology transfer and training platform in Switzerland, (2) the proposition to revisit existing paradigms of modern vaccinology, (3) the properties of polyethyleneimine as potential new vaccine adjuvant, and (4) the progresses in the design of HIV vaccine candidates able to induce broadly neutralizing antibodies.

  17. Enhanced efficacy and immunogenicity of 78kDa antigen formulated in various adjuvants against murine visceral leishmaniasis.

    Science.gov (United States)

    Nagill, Rajeev; Kaur, Sukhbir

    2010-05-21

    Leishmania infection causes localized cutaneous to severe visceral disease in humans and animals. Current control measures, based on antimonial compounds, are not effective because of resistance in Leishmania. Vaccination would be a feasible alternative, but as yet no vaccine to protect humans against infection has been commercialized. Parasite antigens that preferentially stimulate the induction of significant protection through Th1 response presents a rational approach for a vaccine against leishmaniasis. With this view in mind, we investigated the potential of 78kDa antigen of Leishmania donovani alone and along with different adjuvants against murine visceral leishmaniasis. Various adjuvants used along with 78kDa antigen include monophosphoryl lipid A (MPL-A), liposomal encapsulation, recombinant IL-12, autoclaved Leishmania antigen (ALD) and Freund's adjuvant (FCA). BALB/c mice were immunized subcutaneously thrice with respective vaccine formulation. Challenge infection was given intracardially after 2 weeks of second booster. A significant decrease in parasite burden was seen in vaccinees over the infected controls on all post challenge days and was found that maximum protection was provided by 78kDa+rIL-12 vaccine and it was highly immunogenic as depicted by the reduction in parasite load (71-94.8%), reduction in infection rate of peritoneal macrophages (92.9-98%), enhanced DTH response (6.5-10.5 fold), increase in IgG2a anti-leishmanial antibody production (3-3.7 fold) and up-regulation of IFN-gamma (3.7-6.5 fold) and IL-2 levels (7.7-12.3 fold), which demonstrate the generation of protective Th1 type of immune response. Comparable results were also observed in 78kDa+MPL-A and liposome-encapsulated 78kDa vaccines with 56.5-92% and 62.9-93.4% reduction in parasite load respectively. Significant results have also been obtained with 78kDa antigen+ALD, 78kDa antigen+FCA and 78kDa antigen alone group but the protective efficacy was reduced as compared to the

  18. Skin-sparing Helical Tomotherapy vs 3D-conformal Radiotherapy for Adjuvant Breast Radiotherapy: In Vivo Skin Dosimetry Study

    Energy Technology Data Exchange (ETDEWEB)

    Capelle, Lisa [Division of Radiation Oncology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta (Canada); Warkentin, Heather; MacKenzie, Marc [Division of Medical Physics, Cross Cancer Institute and University of Alberta, Edmonton, Alberta (Canada); Joseph, Kurian; Gabos, Zsolt; Pervez, Nadeem; Tankel, Keith; Chafe, Susan [Division of Radiation Oncology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta (Canada); Amanie, John [Division of Statistics and Epidemiology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta (Canada); Ghosh, Sunita; Parliament, Matthew [Division of Radiation Oncology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta (Canada); Abdulkarim, Bassam, E-mail: bassam.abdulkarim@mcgill.ca [Division of Radiation Oncology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta (Canada)

    2012-08-01

    Purpose: We investigated whether treatment-planning system (TPS)-calculated dose accurately reflects skin dose received for patients receiving adjuvant breast radiotherapy (RT) with standard three-dimensional conformal RT (3D-CRT) or skin-sparing helical tomotherapy (HT). Methods and Materials: Fifty patients enrolled in a randomized controlled trial investigating acute skin toxicity from adjuvant breast RT with 3D-CRT compared to skin-sparing HT, where a 5-mm strip of ipsilateral breast skin was spared. Thermoluminescent dosimetry or optically stimulated luminescence measurements were made in multiple locations and were compared to TPS-calculated doses. Skin dosimetric parameters and acute skin toxicity were recorded in these patients. Results: With HT there was a significant correlation between calculated and measured dose in the medial and lateral ipsilateral breast (r = 0.67, P<.001; r = 0.44, P=.03, respectively) and the medial and central contralateral breast (r = 0.73, P<.001; r = 0.88, P<.001, respectively). With 3D-CRT there was a significant correlation in the medial and lateral ipsilateral breast (r = 0.45, P=.03; r = 0.68, P<.001, respectively); the medial and central contralateral breast (r = 0.62, P=.001; r = 0.86, P<.001, respectively); and the mid neck (r = 0.42, P=.04, respectively). On average, HT-calculated dose overestimated the measured dose by 14%; 3D-CRT underestimated the dose by 0.4%. There was a borderline association between highest measured skin dose and moist desquamation (P=.05). Skin-sparing HT had greater skin homogeneity (homogeneity index of 1.39 vs 1.65, respectively; P=.005) than 3D-CRT plans. HT plans had a lower skin{sub V50} (1.4% vs 5.9%, respectively; P=.001) but higher skin{sub V40} and skin{sub V30} (71.7% vs 64.0%, P=.02; and 99.0% vs 93.8%, P=.001, respectively) than 3D-CRT plans. Conclusion: The 3D-CRT TPS more accurately reflected skin dose than the HT TPS, which tended to overestimate dose received by 14% in patients

  19. Trichosanthin functions as Th2-type adjuvant in induction of allergic airway inflammation

    Institute of Scientific and Technical Information of China (English)

    Yuan Wang; Kairui Mao; Shuhui Sun; Guomei Lin; Xiaodong Wu; Gang Yao; Bing Sun

    2009-01-01

    It is important to understand the pathogenesis of asthma induced by natural allergens, which could exclude the interference of artificial adjuvant and provide insights of natural immune response in the disease. In the present study, we show that Trichosanthin (TCS) could induce airway inflammation even without the help of alum. Further-more, TCS appeared capable of replacing alum to promote OVA-specific airway inflammation. TCS induced accu-mulation of IL-4-producing eosinophiis in peritoneum at an early stage and the adjuvant function of TCS was elimi-nated by blockage of IL-4 at this stage. Finally, the eosinophils triggered by TCS from WT mice, but not from IL-4-deficient mice were shown to function as adjuvant for the induction of OVA-specific Th2 responses. Our data indicate that TCS is not only an allergen, but also a Th2-type adjuvant modulating the switching of immune responses to a Th2 pathway. This chain of events results from IL-4 production by eosinophils at an early stage of TCS-priming. In conclusion, TCS may be useful as a Th2 adjuvant, and innate immune cells, such as eosinophils, may be a good target to study the initiation of Th2 response.

  20. CpG-DNA enhancement the immune elicited as adjuvant of foot- and- mouth disease vaccine

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    Morshedi, A.

    2010-01-01

    Full Text Available In the present study the effect of the locally produced genetic adjuvant of ginea pig specific CpG-motif-containing oligodeoxynucleotide (CpG-ODN in an inactivated FMD virus vaccine was evaluated. Boosting the ginea pigs with FMD vaccine along with CpG-ODN adjuvant produced relatively higher ratio (5-fold of FMDV-specific IgG2a / IgG1 than those vaccinated in the absence of CpG-ODN. The neutralizing antibody (NA titer induced by FMD vaccine along with CpG-ODN adjuvant was significantly higher (8-fold than NA titer induced by the classical FMD vaccine in Alum adjuvant. The titer of NA and virus clearance from serum was consistently and significantly higher in animals primed with FMD vaccine and boosted by CpG-ODN than the classical FMD vaccine. The results of this study showed the potential of CpG-ODN as a genetic adjuvant to FMD vaccine in the development of Th1 responses.