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Article ; Online: Mimotope vaccination--from allergy to cancer.

Knittelfelder, Regina / Riemer, Angelika B / Jensen-Jarolim, Erika

2009 Volume 9, Issue 4, Page(s) 493–506

Abstract: Background: Mimotopes are peptides mimicking protein, carbohydrates or lipid epitopes and can be generated by phage display technology. When selected by antibodies, they represent exclusively B-cell epitopes and are devoid of antigen/allergen-specific T- ...

Abstract	Background: Mimotopes are peptides mimicking protein, carbohydrates or lipid epitopes and can be generated by phage display technology. When selected by antibodies, they represent exclusively B-cell epitopes and are devoid of antigen/allergen-specific T-cell epitopes. Coupled to carriers or presented in a multiple antigenic peptide form mimotopes achieve immunogenicity and induce epitope-specific antibody responses upon vaccination. Objective/methods: In allergy IgG antibodies may block IgE binding to allergens, whereas other IgG antibody specificities enhance this and support the anaphylactic reaction. In cancer, inhibitory antibody specificities prevent growth signals derived from overexpressed oncogenes, whereas growth-promoting specificities enhance signalling and proliferation. Therefore, the mimotope concept is applicable to both fields for epitope-specific vaccination and analysis of conformational B-cell epitopes for the allergen/antigen. Results/conclusions: Mimotope technology is a relatively young theme in allergology and oncology. Still, proof of concept studies testing allergen and tumour mimotope vaccines suggest that mimotopes are ready for clinical trials.
MeSH term(s)	Animals ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/immunology ; Epitopes/administration & dosage ; Epitopes/immunology ; Humans ; Hypersensitivity/immunology ; Hypersensitivity/prevention & control ; Neoplasms/immunology ; Neoplasms/prevention & control ; Peptides/administration & dosage ; Peptides/immunology ; Vaccines, Subunit/administration & dosage ; Vaccines, Subunit/immunology
Chemical Substances	Cancer Vaccines ; Epitopes ; Peptides ; Vaccines, Subunit
Language	English
Publishing date	2009-04-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2052501-1
ISSN	1744-7682 ; 1471-2598
ISSN (online)	1744-7682
ISSN	1471-2598
DOI	10.1517/14712590902870386
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Zs.A 6094: Show issues

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Article ; Online: Phase II study on the efficacy and safety of Lapatinib administered beyond disease progression and combined with vinorelbine in HER-2/neu- positive advanced breast cancer: results of the CECOG LaVie trial.

Thallinger, Christiane / Lang, Istvan / Kuhar, Cvetka Grasic / Bartsch, Rupert / Singer, Christian F / Petruzelka, Lubos / Melichar, Bohuslav / Knittelfelder, Regina / Brodowicz, Thomas / Zielinski, Christoph

BMC cancer

2016 Volume 16, Page(s) 121

Abstract: Background: Vinorelbine constitutes effective chemotherapy for metastatic breast cancer (MBC) and acts synergistically with trastuzumab in HER-2/neu positive disease. The present study was set out to evaluate the efficacy and safety of vinorelbine when ... ...

Abstract	Background: Vinorelbine constitutes effective chemotherapy for metastatic breast cancer (MBC) and acts synergistically with trastuzumab in HER-2/neu positive disease. The present study was set out to evaluate the efficacy and safety of vinorelbine when combined with lapatinib, an anti-HER2 tyrosine-kinase inhibitor, as late-line regimen administered beyond previous disease progression on prior lapatinib in patients with HER-2/neu- positive MBC. Methods: The CECOG LaVie study was designed as open-labeled, single-arm, multicenter phase II trial. Patients had to be pretreated with lapatinib plus chemotherapy, and received lapatinib at a daily dose of 1250 mg in combination with vinorelbine 20 mg/m(2) i.v. on days 1 and 8 of a three-week cycle until disease progression, intolerable toxicity or withdrawal of consent. Progression-free survival (PFS) was defined as primary study endpoint; secondary endpoints included overall survival (OS), response rate according to RECIST 1.1, and safety. The study was terminated early due to poor accrual. Results: A total number of nine patients were included; lapatinib administered beyond disease progression combined with vinorelbine resulted in a median PFS of 7.7 months (95% CI 0.56-14.91) and a median OS of 23.4 months (95% CI 16.61-30.13), respectively. Partial remission was seen in one of nine patients, three patients had stable disease of > six months, whereas the remaining five patients had primary disease progression. In two patients, modification of vinorelbine dose due to toxicity became necessary; no dose modification was needed for lapatinib. The majority of reported adverse events (AE) were grade 1 and 2 in severity with diarrhea being the most commonly observed AE CONCLUSION: In this heavily pretreated patient population, combination of vinorelbine plus lapatinib showed encouraging activity and was characterized by an acceptable safety profile. Despite the low patient number, lapatinib plus vinorelbine may constitute a potential treatment option in heavily pretreated patients with HER-2/neu-positive MBC previously exposed to lapatinib. Trial registration: EudraCT number 2009-016826-15, (15. 10.2009).
MeSH term(s)	Adult ; Aged ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Drug Therapy, Combination ; Female ; Humans ; Middle Aged ; Quinazolines/administration & dosage ; Quinazolines/adverse effects ; Quinazolines/therapeutic use ; Receptor, ErbB-2 ; Vinblastine/administration & dosage ; Vinblastine/adverse effects ; Vinblastine/analogs & derivatives ; Vinblastine/therapeutic use
Chemical Substances	Antineoplastic Agents ; Quinazolines ; lapatinib (0VUA21238F) ; Vinblastine (5V9KLZ54CY) ; Receptor, ErbB-2 (EC 2.7.10.1) ; vinorelbine (Q6C979R91Y)
Language	English
Publishing date	2016-02-18
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/s12885-016-2171-y
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Article ; Online: FOLFOX4 Plus Cetuximab for Patients With Previously Untreated Metastatic Colorectal Cancer According to Tumor RAS and BRAF Mutation Status: Updated Analysis of the CECOG/CORE 1.2.002 Study.

Kaczirek, Klaus / Ciuleanu, Tudor E / Vrbanec, Damir / Marton, Erika / Messinger, Diethelm / Liegl-Atzwanger, Bernadette / Wrba, Fritz / Knittelfelder, Regina / Lindner, Elisabeth / Zielinski, Christoph C / Streubel, Berthold / Brodowicz, Thomas

Clinical colorectal cancer

2015 Volume 14, Issue 2, Page(s) 91–98

Abstract: Background: This updated analysis of the CECOG/CORE 1.2.002 study investigated the association between clinical outcome and RAS and BRAF mutations in metastatic colorectal cancer (mCRC) patients treated with FOLFOX4 plus cetuximab.: Patients and ... ...

Abstract	Background: This updated analysis of the CECOG/CORE 1.2.002 study investigated the association between clinical outcome and RAS and BRAF mutations in metastatic colorectal cancer (mCRC) patients treated with FOLFOX4 plus cetuximab. Patients and methods: Available DNA samples from CECOG/CORE 1.2.002 study patients with KRAS exon 2 wild type (wt) (at codons 12 and 13) tumors were screened for mutations at other loci in the KRAS and NRAS (RAS) coding regions by Sanger sequencing, and for BRAF codon 600 mutations by Sanger sequencing and pyrosequencing. Clinical outcome was compared among different mutation subgroups. Results: Of 152 KRAS wt mCRC patients, 148 were evaluable for RAS and BRAF mutation status. Eleven RAS mutations were detected in 10 patients' tumors (7%). BRAF mutations were detected in 14 patients' tumors (9%). RAS and BRAF tumor mutations were mutually exclusive. Compared with patients with RAS wt/BRAF wt tumors (n = 124; median overall survival, 28.5 months), those with RAS mutations (n = 10; median, 16.3 months; hazard ratio, 0.43; 95% confidence interval, 0.20-0.89; P = .020) or BRAF mutations (n = 14; median, 11.7 months; hazard ratio, 0.23; 95% confidence interval, 0.12-0.41; P < .0001) had worse overall survival, which remained significant (P < .04) when adjusting for differences in baseline characteristics among the mutation subgroups. Conclusion: These findings support those from recent studies that RAS and BRAF mutations are associated with poor outcome in patients receiving an epidermal growth factor receptor-targeted monoclonal antibody in combination with oxaliplatin-based chemotherapy. Furthermore, mutation testing should not only include RAS codons 12 and 13 but should also be extended to the entire coding regions.
MeSH term(s)	Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cetuximab/administration & dosage ; Codon/genetics ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/mortality ; Colorectal Neoplasms/pathology ; Female ; Fluorouracil/administration & dosage ; Follow-Up Studies ; GTP Phosphohydrolases/genetics ; Humans ; Leucovorin/administration & dosage ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/mortality ; Liver Neoplasms/secondary ; Male ; Membrane Proteins/genetics ; Middle Aged ; Mutation/genetics ; Neoplasm Staging ; Organoplatinum Compounds/administration & dosage ; Prognosis ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins p21(ras) ; Retrospective Studies ; Survival Rate ; ras Proteins/genetics
Chemical Substances	Codon ; KRAS protein, human ; Membrane Proteins ; Organoplatinum Compounds ; Proto-Oncogene Proteins ; oxaliplatin (04ZR38536J) ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; GTP Phosphohydrolases (EC 3.6.1.-) ; NRAS protein, human (EC 3.6.1.-) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; ras Proteins (EC 3.6.5.2) ; Cetuximab (PQX0D8J21J) ; Leucovorin (Q573I9DVLP) ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2015-06
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2112638-0
ISSN	1938-0674 ; 1533-0028
ISSN (online)	1938-0674
ISSN	1533-0028
DOI	10.1016/j.clcc.2014.12.003
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Zs.A 5798: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Anti-idiotypic Fab Fragments Image a Conserved N-terminal Epitope Patch of Grass Pollen Allergen Phl p 1.

Lukschal, Anna / Fuhrmann, Jan / Sobanov, Juryj / Neumann, Dirk / Wallmann, Julia / Knittelfelder, Regina / Hemmer, Wolfgang / Scheiner, Otto / Vogel, Monique / Stadler, Beda M / Jensen-Jarolim, Erika / Szalai, Krisztina

The open allergy journal

2012 Volume 4, Page(s) 16–23

Abstract: BACKGROUND AND AIMS: Naturally occurring anti-idiotypic antibodies structurally mimic the original antibody epitope. Anti-idiotypes, therefore, are interesting tools for the portrayal of conformational B-cell epitopes of allergens. In this study we used ... ...

Abstract	BACKGROUND AND AIMS: Naturally occurring anti-idiotypic antibodies structurally mimic the original antibody epitope. Anti-idiotypes, therefore, are interesting tools for the portrayal of conformational B-cell epitopes of allergens. In this study we used this strategy particularly for major timothy grass pollen (Phleum pratense) allergen Phl p 1. METHODS AND RESULTS: We used a combinatorial phage display library constructed from the peripheral IgG repertoire of a grass pollen allergic patient which was supposed to contain anti-idiotypic Fab specificities. Using purified anti-Phl p 1 IgG for biopanning, several Fab displaying phage clones could be isolated. 100 amplified colonies were screened for their binding capacity to anti-Phl p 1-specific antibodies, finally resulting in four distinct Fab clones according to sequence analysis. Interestingly, heavy chains of all clones derived from the same germ line sequence and showed high homology in their CDRs. Projecting their sequence information on the surface of the natural allergen Phl p 1 (PDB ID: 1N10) indicated matches on the N-terminal domain of the homo-dimeric allergen, including the bridging region between the two monomers. The resulting epitope patches were formed by spatially distant sections of the primary allergen sequence. CONCLUSION: In this study we report that anti-idiotypic specificities towards anti-Phl p 1 IgG, selected from a Fab library of a grass pollen allergic patient, mimic a conformational epitope patch being distinct from a previously reported IgE epitope area.
Language	English
Publishing date	2012-02-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2575248-0
ISSN	1874-8384
ISSN	1874-8384
DOI	10.2174/1874838401104010016
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Article ; Online: Cetuximab-based or bevacizumab-based first-line treatment in patients with KRAS p.G13D-mutated metastatic colorectal cancer: a pooled analysis.

Modest, Dominik Paul / Reinacher-Schick, Anke / Stintzing, Sebastian / Giessen, Clemens / Tannapfel, Andrea / Laubender, Ruediger Paul / Brodowicz, Thomas / Knittelfelder, Regina / Vrbanec, Damir / Schmiegel, Wolff / Heinemann, Volker / Zielinski, Christoph C

Anti-cancer drugs

2012 Volume 23, Issue 6, Page(s) 666–673

Abstract: KRAS p.G13D mutant metastatic colorectal cancer (mCRC) has been identified as representing a cetuximab-sensitive subtype of KRAS mutant mCRC. This analysis aims to answer the question of whether first-line treatment of p.G13D mCRCs should include ... ...

Abstract	KRAS p.G13D mutant metastatic colorectal cancer (mCRC) has been identified as representing a cetuximab-sensitive subtype of KRAS mutant mCRC. This analysis aims to answer the question of whether first-line treatment of p.G13D mCRCs should include cetuximab or bevacizumab. Fifty-four patients with p.G13D mutant mCRC were pooled in this analysis. All patients underwent systemic first-line treatment with a fluoropyrimidine and oxaliplatin/irinotecan that was combined with either cetuximab or bevacizumab. The analysis of cetuximab-based and bevacizumab-based regimens in mCRC patients with p.G13D-mutated tumours indicated comparable data for the overall response rate (58 vs. 57%) and progression-free survival (8.0 vs. 8.7 months; hazard ratio: 0.96, P=0.9). Overall survival (OS) was 20.1 months in patients treated with cetuximab-based first-line therapy compared with 14.9 months in patients receiving bevacizumab-containing regimens (hazard ratio: 0.70, P=0.29). Logistic regressions modelling OS revealed oxaliplatin-based first-line treatment to correlate with a poor outcome (P=0.03). Moreover, a strong trend in favour of capecitabine compared with infusional 5-FU (P=0.06) was observed. Response to treatment correlated with OS in patients receiving cetuximab-based, but not bevacizumab-based regimens. This retrospective pooled analysis suggests comparable efficacy of cetuximab-based and bevacizumab-based first-line therapy in patients with p.G13D mutant mCRC. The combination with capecitabine and irinotecan was associated with a more favourable outcome compared with infusional 5-FU and oxaliplatin.
MeSH term(s)	Adult ; Aged ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab ; Camptothecin/administration & dosage ; Camptothecin/analogs & derivatives ; Capecitabine ; Cetuximab ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/mortality ; Colorectal Neoplasms/pathology ; Deoxycytidine/administration & dosage ; Deoxycytidine/analogs & derivatives ; Disease-Free Survival ; Female ; Fluorouracil/administration & dosage ; Fluorouracil/analogs & derivatives ; Humans ; Logistic Models ; Male ; Middle Aged ; Mutation ; Organoplatinum Compounds/administration & dosage ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins p21(ras) ; Retrospective Studies ; ras Proteins/genetics
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; KRAS protein, human ; Organoplatinum Compounds ; Proto-Oncogene Proteins ; oxaliplatin (04ZR38536J) ; Deoxycytidine (0W860991D6) ; Bevacizumab (2S9ZZM9Q9V) ; Capecitabine (6804DJ8Z9U) ; irinotecan (7673326042) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; ras Proteins (EC 3.6.5.2) ; Cetuximab (PQX0D8J21J) ; Fluorouracil (U3P01618RT) ; Camptothecin (XT3Z54Z28A)
Language	English
Publishing date	2012-07
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1065301-6
ISSN	1473-5741 ; 0959-4973
ISSN (online)	1473-5741
ISSN	0959-4973
DOI	10.1097/CAD.0b013e328352ff1d
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Article ; Online: Impact of the specific mutation in KRAS codon 12 mutated tumors on treatment efficacy in patients with metastatic colorectal cancer receiving cetuximab-based first-line therapy: a pooled analysis of three trials.

Modest, Dominik P / Brodowicz, Thomas / Stintzing, Sebastian / Jung, Andreas / Neumann, Jens / Laubender, Ruediger P / Ocvirk, Janja / Kurteva, Galina / Papai, Zsuzsanna / Knittelfelder, Regina / Kirchner, Thomas / Heinemann, Volker / Zielinski, Christoph C

Oncology

2012 Volume 83, Issue 5, Page(s) 241–247

Abstract: Purpose: This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras (KRAS) gene on treatment efficacy in patients with metastatic colorectal cancer (mCRC).: Patients: Overall, 119 patients bearing a KRAS mutation in codon ...

Abstract	Purpose: This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras (KRAS) gene on treatment efficacy in patients with metastatic colorectal cancer (mCRC). Patients: Overall, 119 patients bearing a KRAS mutation in codon 12 were evaluated. All patients received cetuximab-based first-line chemotherapy within the Central European Cooperative Oncology Group (CECOG), AIO KRK-0104 or AIO KRK-0306 trials. Results: Patients with KRAS codon 12 mutant mCRC showed a broad range of outcome when treated with cetuximab-based first-line regimens. Patients with tumors bearing a KRAS p.G12D mutation showed a strong trend to a more favorable outcome compared to other mutations (overall survival 23.3 vs. 14-18 months; hazard ratio 0.66, range 0.43-1.03). An interaction model illustrated that KRAS p.G12C was associated with unfavorable outcome when treated with oxaliplatin plus cetuximab. Conclusion: The present analysis suggests that KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when treated with cetuximab-based first-line therapy.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Camptothecin/administration & dosage ; Camptothecin/analogs & derivatives ; Capecitabine ; Cetuximab ; Codon/drug effects ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Deoxycytidine/administration & dosage ; Deoxycytidine/analogs & derivatives ; Drug Administration Schedule ; Female ; Fluorouracil/administration & dosage ; Fluorouracil/analogs & derivatives ; Germany ; Humans ; Leucovorin/administration & dosage ; Male ; Middle Aged ; Multicenter Studies as Topic ; Mutation ; Odds Ratio ; Organoplatinum Compounds/administration & dosage ; Prognosis ; Proto-Oncogene Proteins/drug effects ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins p21(ras) ; Randomized Controlled Trials as Topic ; Treatment Outcome ; ras Proteins/drug effects ; ras Proteins/genetics
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Codon ; KRAS protein, human ; Organoplatinum Compounds ; Proto-Oncogene Proteins ; oxaliplatin (04ZR38536J) ; Deoxycytidine (0W860991D6) ; Capecitabine (6804DJ8Z9U) ; irinotecan (7673326042) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; ras Proteins (EC 3.6.5.2) ; Cetuximab (PQX0D8J21J) ; Leucovorin (Q573I9DVLP) ; Fluorouracil (U3P01618RT) ; Camptothecin (XT3Z54Z28A)
Language	English
Publishing date	2012
Publishing country	Switzerland
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
ZDB-ID	250101-6
ISSN	1423-0232 ; 0030-2414
ISSN (online)	1423-0232
ISSN	0030-2414
DOI	10.1159/000339534
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Article: Active induction of tumor-specific IgE antibodies by oral mimotope vaccination.

Riemer, Angelika B / Untersmayr, Eva / Knittelfelder, Regina / Duschl, Albert / Pehamberger, Hubert / Zielinski, Christoph C / Scheiner, Otto / Jensen-Jarolim, Erika

Cancer research

2007 Volume 67, Issue 7, Page(s) 3406–3411

Abstract: A role of IgE antibodies in cancer surveillance has been implicated for a long time. Studies dealing with IgE antibodies directly targeted to tumor antigens have shown marked anticancer effects mediated by this antibody class. Thus, the basic function of ...

Abstract	A role of IgE antibodies in cancer surveillance has been implicated for a long time. Studies dealing with IgE antibodies directly targeted to tumor antigens have shown marked anticancer effects mediated by this antibody class. Thus, the basic function of IgE antibodies may be to control tumor growth. Thus far, cancer-specific IgE has only been applied passively. Consequently, the aim of this study was to establish an active vaccination protocol to induce tumor antigen-specific IgE antibodies, and to evaluate functional properties. We previously generated epitope mimics, so-called mimotopes, for the epitope recognized by the anti-HER-2 antibody trastuzumab. Upon i.p. immunizations, IgG antibodies with trastuzumab-like properties could be elicited. In the present study, we immunized BALB/c mice via the oral route with these trastuzumab mimotopes, under simultaneous neutralization and suppression of gastric acid. As shown in preceding experiments, this feeding regimen effectively induces Th2 immune responses. Oral immunizations with trastuzumab mimotopes under hypoacidic conditions indeed resulted in the formation of IgE antibodies towards the HER-2 antigen. Moreover, anti-HER-2 IgE-sensitized effector cells mediated SK-BR-3 target cell lysis in an antibody-dependent cytotoxicity assay. We conclude that directed and epitope-specific induction of IgE against tumor antigens is feasible with an oral mimotope vaccination regimen, and that these antibodies mediate anticancer effects.
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm/biosynthesis ; Antibodies, Neoplasm/immunology ; Antibody Specificity ; Breast Neoplasms/immunology ; Breast Neoplasms/therapy ; Cancer Vaccines/immunology ; Cancer Vaccines/pharmacology ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; Epitopes/immunology ; Humans ; Immunoglobulin E/biosynthesis ; Immunoglobulin E/immunology ; Rats ; Receptor, ErbB-2/immunology ; Trastuzumab
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm ; Cancer Vaccines ; Epitopes ; Immunoglobulin E (37341-29-0) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK)
Language	English
Publishing date	2007-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-06-3758
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Article: The Fc gammaRIIa polymorphism R/H131, autoantibodies against the platelet receptors GPIb alpha and Fc gammaRIIa and a risk for thromboembolism in lupus anticoagulant patients.

Schallmoser, Katharina / Rosin, Christiane / Knittelfelder, Regina / Sailer, Thomas / Ulrich, Silvia / Zoghlami, Claudia / Lehr, Stephan / Pabinger, Ingrid / Panzer, Simon

Thrombosis and haemostasis

2005 Volume 93, Issue 3, Page(s) 544–548

Abstract: There is a clear propensity of individuals with lupus anticoagulant (LA) for thromboembolic disease (TE). Yet, it is not clear how individuals at risk for TE can be differentiated from those who are not. The Fc gammaRIIa receptor is the only Fc receptor ... ...

Abstract	There is a clear propensity of individuals with lupus anticoagulant (LA) for thromboembolic disease (TE). Yet, it is not clear how individuals at risk for TE can be differentiated from those who are not. The Fc gammaRIIa receptor is the only Fc receptor expressed by platelets. As platelets can be activated via this receptor, we have compared gene frequencies of the Fc gammaRIIa polymorphism R/H131 in 46 and 27 patients with (LA/TE+) and without TE (LA/TE-), respectively, in an exploratory study. Furthermore, we investigated the presence of autoantibodies against Fc gammaRIIa and/or GPIb alpha, which is in close proximity to the Fc gammaRIIa and interacts with it functionally, and a possible linkage of antibody formation to HLA class II alleles. The Fc gammaRIIa-R/R131 genotype was significantly less frequent in patients with LA compared to controls (p<0.025). These findings were due to an increased frequency of heterozygous patients in the LA/TE+ cohort (odds ratio 6.76, 95% confidence interval 1.55-62.03, p<0.008). For the first time, heterozygosity, rather than homozygosity, can be linked to disease, which may be explained by the dual function of the Fc gammaRIIa, namely binding of antibodies to platelets and thereby their activation, and, on the other hand, clearance of antibody coated platelets by the phagocyte system. There was no correlation between the presence of anti-Fc gammaRIIa or anti-GPIb alpha autoantibodies and the Fc gammaRIIa-R/H131 polymorphism, nor the incidence of TE, nor HLA class II alleles.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Autoantibodies/blood ; Case-Control Studies ; Child ; Gene Frequency ; Heterozygote ; Homozygote ; Humans ; Lupus Coagulation Inhibitor ; Membrane Glycoproteins ; Membrane Proteins/immunology ; Middle Aged ; Mutation, Missense ; Odds Ratio ; Platelet Glycoprotein GPIb-IX Complex ; Polymorphism, Genetic ; Receptors, Fc/genetics ; Receptors, Fc/immunology ; Receptors, Fc/physiology ; Receptors, IgG/genetics ; Receptors, IgG/immunology ; Risk ; Thromboembolism/etiology ; Thromboembolism/genetics ; Thromboembolism/immunology
Chemical Substances	Autoantibodies ; Fc gamma receptor IIA ; Lupus Coagulation Inhibitor ; Membrane Glycoproteins ; Membrane Proteins ; Platelet Glycoprotein GPIb-IX Complex ; Receptors, Fc ; Receptors, IgG ; adhesion receptor
Language	English
Publishing date	2005-03
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	518294-3
ISSN	0340-6245
ISSN	0340-6245
DOI	10.1160/TH04-07-0428
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Article: Impact of the Specific Mutation in ; Codon 12 Mutated Tumors on Treatment Efficacy in Patients with Metastatic Colorectal Cancer Receiving Cetuximab-Based First-Line Therapy: A Pooled Analysis of Three Trials

Modest, Dominik P. / Brodowicz, Thomas / Stintzing, Sebastian / Jung, Andreas / Neumann, Jens / Laubender, Ruediger P. / Ocvirk, Janja / Kurteva, Galina / Papai, Zsuzsanna / Knittelfelder, Regina / Kirchner, Thomas / Heinemann, Volker / Zielinski, Christoph C.

Oncology

2012 Volume 83, Issue 5, Page(s) 241–247

Abstract: Purpose: This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras (KRAS) gene on treatment efficacy in patients with metastatic colorectal cancer (mCRC). Patients: Overall, 119 patients bearing a KRAS mutation in codon 12 ... ...

Institution	Department of Medicine III, University Hospital Grosshadern, and Institutes of Pathology and Medical Informatics, Biometry, and Epidemiology, University of Munich, Munich, Germany Central European Cooperative Oncology Group, and Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria Institute of Oncology, Ljubljana, Slovenia SBALO National Oncology Center, Sofia, Bulgaria AEK Onkologiai Osztaly, Budapest, Hungary
Abstract	Purpose: This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras (KRAS) gene on treatment efficacy in patients with metastatic colorectal cancer (mCRC). Patients: Overall, 119 patients bearing a KRAS mutation in codon 12 were evaluated. All patients received cetuximab-based first-line chemotherapy within the Central European Cooperative Oncology Group (CECOG), AIO KRK-0104 or AIO KRK-0306 trials. Results: Patients with KRAS codon 12 mutant mCRC showed a broad range of outcome when treated with cetuximab-based first-line regimens. Patients with tumors bearing a KRAS p.G12D mutation showed a strong trend to a more favorable outcome compared to other mutations (overall survival 23.3 vs. 14–18 months; hazard ratio 0.66, range 0.43–1.03). An interaction model illustrated that KRAS p.G12C was associated with unfavorable outcome when treated with oxaliplatin plus cetuximab. Conclusion: The present analysis suggests that KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when treated with cetuximab-based first-line therapy.
Keywords	Metastatic colorectal cancer ; mutation ; Codon 12 ; Cetuximab ; Anti-epidermal growth factor receptor
Language	English
Publishing date	2012-08-29
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Clinical Translational Research
ZDB-ID	250101-6
ISSN	1423-0232 ; 0030-2414
ISSN (online)	1423-0232
ISSN	0030-2414
DOI	10.1159/000339534
Database	Karger publisher's database

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Article ; Online: Nitration of ovalbumin decreases the risk for sensitization via the oral route in a mouse food allergy model

Diesner Susanne C / Untersmayr Eva / Oostingh Gertie J / Selzle Kathrin / Pfaller Tobias / Schultz Cornelia / Zhang Yingyi / Krishnamurthy Durga / Starkl Philipp / Knittelfelder Regina / Förster-Waldl Elisabeth / Pollak Arnold / Scheiner Otto / Pöschl Ulrich / Jensen-Jarolim Erika / Duschl Albert

Clinical and Translational Allergy, Vol 1, Iss Suppl 1, p O

2011 Volume 49

Keywords	Immunologic diseases. Allergy ; RC581-607 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Allergy and Immunology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2011-08-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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