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  • 1
    In: Journal of Allergy and Clinical Immunology, Elsevier BV, Vol. 137, No. 2 ( 2016-02), p. 601-609.e8
    Type of Medium: Online Resource
    ISSN: 0091-6749
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 2006613-2
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  • 2
    In: International Journal of Gynecologic Cancer, BMJ, Vol. 30, No. 11 ( 2020-11), p. 1667-1671
    Abstract: On March 16, 2020, the federal government of Austria declared a nationwide lockdown due to the COVID-19 pandemic. Since the lockdown, screening examinations and routine checkups have been restricted to prevent the spread of the virus and to increase the hospitals’ bed capacity across the country. This resulted in a severe decline of patient referrals to the hospitals. Objective To assess the impact of the COVID-19 pandemic on the rate of newly diagnosed gynecological and breast cancers in Austria. Methods Data of 2077 patients from 18 centers in Austria with newly diagnosed gynecological or breast cancer between January and May 2019 and January and May 2020 were collected. Clinical parameters, including symptoms, performance status, co-morbidities, and referral status, were compared between the time before and after the COVID-19 outbreak. Results Our results showed a slight increase of newly diagnosed cancers in January and February 2020 as compared with 2019 (+2 and +35%, respectively) and a strong decline in newly diagnosed tumors since the lockdown: −24% in March 2020 versus March 2019, −49% in April 2020 versus April 2019, −49% in May 2020 versus May 2019. Two-thirds of patients diagnosed during the pandemic presented with tumor-specific symptoms compared with less than 50% before the pandemic (p 〈 0.001). Moreover, almost 50% of patients in 2020 had no co-morbidities compared with 35% in 2019 (p 〈 0.001). Patients, who already had a malignant disease, were rarely diagnosed with a new cancer in 2020 as compared with 2019 (11% vs 6%; p 〈 0.001). Conclusions The lockdown led to a decreased number of newly diagnosed gynecological and breast cancers. The decreased accessibility of the medical services and postponed diagnosis of potentially curable cancers during the COVID-19 pandemic may be a step backwards in our healthcare system and might impair cancer treatment outcomes. Therefore, new strategies to manage early cancer detection are needed to optimize cancer care in a time of pandemic in the future.
    Type of Medium: Online Resource
    ISSN: 1048-891X , 1525-1438
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2009072-9
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e17592-e17592
    Abstract: e17592 Background: In TCGA data BRCA1 meth was found to be inferior to BRCAmut regarding prognosis in high-grade ovarian cancer. This was explained by a probably lower sensitivity to platinum-based chemotherapy. Methods: In 151 high-grade epithelial ovarian cancers (HGOC) tested for BRCA status, BRCA DNA methylation was determined using MethyLight PCR. Additionally, genome-wide loss of heterozygosity (LOH) and Aneuploidy Normalized Telemetric imbalance (ANTI) by means of SNP-Array analysis (GSA-24 v 3.0/Ilumina) as surrogates for “genomic scaring” in BRCA-independent HRD. For both parameters a “clinical-threshold” was calculated on the basis of platinum-response determined at the first recurrence according to the platinum-free interval. Both variables were integrated in a common HRD-Score with a cut-off value of ≥ 10.3 for HRD positivity. Results: In the present cohort PFS of BRCA1 meth HGOC (n = 15; 10%) was not revealed to be inferior to BRCAmut HGOC. Worst PFS was observed in the subgroup of BRCAwt-unmethylated HGOC (p = 0.013) as compared to HGOC with genetic and epigenetic BRCA alterations. In line, neither LOH nor ANTI and consecutively also HRD-Score did prove to be statistically different in BRCAmut - and BRCA1meth-HGOC. However, BRCAwt-unmethylated HGOC exhibited significantly lower HRD-, LOH- and ANTI-Scores when compared with BRCAmut (p 〈 0.001) and BRCA1 meth -HGOC (p 〈 0.005). All but one of the HGOC classified as platinum-refractory or -resistant at first relapse (92%) were BRCAwt-unmethylated. None of the BRCA1 meth cancers were rated platinum-refractory or -resistant at progression and only one of the BRCAmut cancers was associated with platinum-resistant first relapse. 99% of the recurrences from HGOC with genetically or epigenetically altered BRCA genes were platinum sensitive, from which 78% were classified as “high-sensitive”. In multivariate analysis, HRD-Score was found to be of independent prognostic significance regarding PFS (p = 0.022); this was mainly due to the prognostic power of ANTI-Score (multivariate: p = 0.014) but not to that of genome wide LOH (univariate: p = 0.771). Conclusions: HGOC without genetic or epigenetic BRCA alterations exhibit the most unfavorable PFS. This is related to impaired platinum sensitivity. From a clinical point of view BRCA1 promotor methylation seems to confer an equivalent detrimental effect on the homologous recombination DNA repair mechanism than do pathogenic mutations of the BRCA genes. This is corroborated by a nearly identical extent of genome-wide scaring in both cancer subgroups.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 5605-5605
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 5605-5605
    Abstract: 5605 Background: Based on two randomized trials (LACE and LAP2) minimal invasive surgery has turned into the surgical standard in early stage endometrial cancer including “high-risk” patients. However, these recommendations are predominately based on “low-risk” cancers, which are mainly represented in both trial collectives. We herein provide a retrospective study, which focuses on potential differences in clinical outcome in early stage endometrioid endometrial cancers with distinct risk constellations treated by laparoscopy or open surgery. Methods: 420 early stage endometrial cancers were retrospectively dichotomized according to the surgical approach and correlated to the recurrence rate and clinical outcome. In addition, subgroup analyses were performed according relevant clinical risk parameters, namely FIGO stage, grading and LVSI. Results: The analyzed collective consisted of 73.8% stage IA, 19.5% stage IB, and 6.7% stage II cases. Twenty-tree percent of patients exhibit G3 tumors and LVSI was detected in 12.4%. Minimal invasive surgery was performed in 54.5% of study patients. During a median follow-up of 5.0 years, recurrence or death were observed in 8.3% and 6.7%, respectively. Recurrences were predominately located in the vaginal cuff (n = 21; 60.0%), to a minor extent in loco-regional lymph nodes (n = 11; 31.4%), and in three patients (8.6%) in both sides. No distant metastases were detected at first recurrence. Also under consideration of the mentioned clinicopathologic parameters, the surgical approach in FIGO stage I did not influence the recurrence rate and patients’ survival. However, in a subgroup analysis of stage II disease, the laparoscopic approach was clearly associated with a significant higher recurrence rate (85.7% vs. 14.3%; p = 0.013). All of the recurrences were located in the vaginal cuff, and in one case, additional relapse was found in loco-regional lymph nodes. Moreover, laparoscopic surgery in stage II disease was associated with impaired progression-free and overall survival (HR 8.86 (1.008 – 20.85) and HR 6.36 (1.102 – 28.61), respectively). Conclusions: We herein demonstrate that a minimal invasive surgical approach in stage II endometrial cancer is associated with higher recurrence rates and impaired clinical outcome. These data could be interpreted to be in line with the results of the LACC trial in cervical cancer. Although, grounded on a retrospective analysis, these hypothesis-generating results warrants a confirmatory trial, which is ongoing in a much larger collective of stage II endometrial cancer patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 186, No. 9 ( 2011-05-01), p. 5333-5344
    Abstract: Allergic inflammation is based on the cross-linking of mast cell and basophil-bound IgE Abs and requires at least two binding sites for IgE on allergens, which are difficult to characterize because they are often conformational in nature. We studied the IgE recognition of birch pollen allergen Bet v 1, a major allergen for & gt;100 million allergic patients. Monoclonal and polyclonal Abs raised against Bet v 1-derived peptides were used to compete with allergic patients’ IgE binding to Bet v 1 to search for sequences involved in IgE recognition. Strong inhibitions of patients’ IgE binding to Bet v 1 (52–75%) were obtained with mAbs specific for two peptides comprising aa 29–58 (P2) and aa 73–103 (P6) of Bet v 1. As determined by surface plasmon resonance, mAb2 specific for P2 and mAb12 specific for P6 showed high affinity, but only polyclonal rabbit anti-P2 and anti-P6 Abs or a combination of mAbs inhibited allergen-induced basophil degranulation. Thus, P2 and P6 define a surface patch on the Bet v 1 allergen, which allows simultaneous binding of several different IgE Abs required for efficient basophil and mast cell activation. This finding explains the high allergenic activity of the Bet v 1 allergen. The approach of using peptide-specific Abs for the mapping of conformational IgE epitopes on allergens may be generally applicable. It may allow discriminating highly allergenic from less allergenic allergen molecules and facilitate the rational design of active and passive allergen-specific immunotherapy strategies.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2011
    detail.hit.zdb_id: 1475085-5
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  • 6
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 190, No. 7 ( 2013-04-01), p. 3068-3078
    Abstract: Allergen-specific immunotherapy is the only allergen-specific and disease-modifying treatment for allergy. The construction and characterization of a vaccine for birch pollen allergy is reported. Two nonallergenic peptides, PA and PB, derived from the IgE-reactive areas of the major birch pollen allergen Bet v 1 were fused to the hepatitis B surface protein, PreS, in four recombinant fusion proteins containing different numbers and combinations of the peptides. Fusion proteins expressed in Escherichia coli and purified to homogeneity showed a lack of IgE reactivity and allergenic activity when tested with sera and basophils from patients allergic to birch pollen. Compared to Bet v 1 allergen, peptides PA and PB showed reduced T cell activation in PBMCs from allergic patients, whereas PreS fusion proteins induced less IL-5 and more IL-10 and IFN-γ. Immunization of rabbits with the fusion proteins, in particular with a PreS fusion protein 2PAPB-PreS, containing two copies of each peptide, induced high levels of IgG Abs against the major IgE-reactive site on Bet v 1 and related allergens. These IgG Abs inhibited allergic patients’ IgE binding to Bet v 1 better than did IgG induced by immunization with complete Bet v 1. Furthermore, 2PAPB-PreS–induced IgG inhibited Bet v 1–induced basophil activation in allergic patients and CD23-facilitated allergen presentation. Our study exemplifies novel beneficial features for a PreS carrier–based peptide vaccine for birch pollen, which, in addition to the established reduction in allergenic activity, include the enhanced focusing of blocking Ab responses toward IgE epitopes, immunomodulatory activity, and reduction of CD23-facilitated allergen presentation.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2013
    detail.hit.zdb_id: 1475085-5
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  • 7
    Online Resource
    Online Resource
    S. Karger AG ; 2012
    In:  International Archives of Allergy and Immunology Vol. 159, No. 1 ( 2012), p. 15-22
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 159, No. 1 ( 2012), p. 15-22
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Dasatinib is a multikinase inhibitor active against several tyrosine kinases including ABL, KIT, Lyn and Btk. Apart from its known antileukemic activity, the drug produces several side effects including edemas and pleural effusions, which are supposedly triggered by activated immune cells. Effusion formation can be treated effectively by glucocorticosteroids. We have recently shown that low concentrations of dasatinib ( 〈 0.1 µ 〈 i 〉 M 〈 /i 〉 ) promote IgE-dependent secretion of histamine in basophils, especially in allergic individuals. In the current study, we asked whether glucocorticosteroids inhibit dasatinib-induced activation of basophils. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Basophils were preincubated with dexamethasone, prednisolone and hydrocortisone for 24 h, and were then exposed to an anti-IgE antibody (normal basophils) or the allergens Bet v 1 and Phl p 5 (allergic patients) with or without low concentrations of dasatinib (0.025 µ 〈 i 〉 M 〈 /i 〉 ). After incubation, basophils were examined for histamine release and expression of CD63 and CD203c. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 All three glucocorticosteroids were found to counteract IgE-dependent and dasatinib-enhanced histamine release in basophils in nonallergic and allergic individuals. In addition, glucocorticosteroids were found to inhibit anti-IgE-induced upregulation of CD63 and CD203c in the presence or absence of dasatinib. The inhibitory effects of glucocorticosteroids were dose-dependent (effective range: 1–10 µ 〈 i 〉 M 〈 /i 〉 ) and seen in all donors examined. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Glucocorticosteroids rescue IgE receptor cross-linked basophils from additional costimulatory effects of low-dose dasatinib which may have clinical implications in dasatinib-treated patients.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2012
    detail.hit.zdb_id: 1482722-0
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  • 8
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 18_Supplement ( 2020-09-15), p. PO-038-PO-038
    Abstract: A nationwide lockdown was declared on March 16 in Austria due to coronavirus disease 2019 (COVID-19) outbreak, requiring citizens to remain in their homes except for necessary reasons. The lockdown resulted not only in social distancing and reduction of commercial activity, but also in severe restrictions in the health care system. Regular medical services and outpatient care were nearly shut down to prevent the spread of the virus and to increase the total hospital capacities. Thus, patients faced barriers to attend preventive checkups, such as mammography, screening for cervical cancer, or to consult the general practitioner. As a gynecologic department with a large oncologic subunit, we noticed significantly fewer tumor diagnoses presenting at our department since the lockdown. This phenomenon forced us to perform this retrospective study on newly diagnosed gynecologic and breast cancers before and during the COVID-19 pandemic. A retrospective analysis of newly diagnosed gynecologic and breast cancers presented at the University Hospital Innsbruck from January to May 2019 and from January to May 2020 was performed. Descriptive statistics and analysis of the clinical data stratified by the year of diagnosis were performed using SPSS software and Mann-Whitney U test. Our results showed a slight increase of newly diagnosed cancers in January and February 2020 as compared to 2019 (+13%) and a strong decline in newly diagnosed tumors since the lockdown: -45% in March 2020 vs. March 2019, -63% in April 2020 vs. April 2019, and -44% in May 2020 vs. May 2019. Around two third of patients diagnosed during the pandemic consulted the specialist due to tumor symptoms, while before the pandemic less than 50% of patients presented with symptoms. The ratio of breast and vulvar cancer was significantly higher during the pandemic (71 vs. 61% and 3 vs. 1.9%, respectively; p=0.043), but significantly fewer cervical cancers were diagnosed (4.4 vs. 8.9%; p=0.043). Patients with other malignant, rheumatic, or metabolic disease were rarely diagnosed with a new cancer in 2020 as compared to 2019 (7.5 vs. 12%; 0.7 vs. 3.7% and 6.7 vs. 12%, respectively; p=0.014). A better performance status was observed in patients presented in 2020 as compared to 2019 (p=0.011). In a country with maximum intensive care bed occupancy of 26% during the COVID-19 pandemic, the accessibility of the health care services was severely impaired and preventive care and early cancer detection was restricted, leading to an increase in undetected or postponed tumor diagnoses. The aim of our work is to raise awareness of this issue. It is not clear whether these undetected cases will lead to potential months of life lost; however, decreased accessibility of the medical services and postponed diagnosis of potentially curable cancers are clearly a step backwards in our health care system and will probably impair cancer treatment outcomes. Thus, new strategies to manage early cancer detection are needed to optimize cancer care in a time of pandemic in the future. Citation Format: Irina Tsibulak, Elisabeth Reiser, Christoph Ebner, Katharina Knoll, Katharina Leitner, Verena Wieser, Justina Angerer, Christian Marth. Strong decline of newly diagnosed gynecologic and breast cancers during the COVID-19 pandemic: A retrospective analysis from Innsbruck, Austria [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-038.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 9
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  Archives of Gynecology and Obstetrics Vol. 305, No. 4 ( 2022-04), p. 945-953
    In: Archives of Gynecology and Obstetrics, Springer Science and Business Media LLC, Vol. 305, No. 4 ( 2022-04), p. 945-953
    Abstract: The aim of the present study was to assess the impact of postponed screening examinations and lockdown measures on gynecological and breast cancer diagnoses throughout the year 2020 in a gynecological oncological center in Austria. Methods Data of 889 patients with either newly diagnosed gynecological or breast cancer between January 2019 and December 2020 were collected. Clinical parameters including symptoms, performance status, comorbidities and referral status were compared in patients, who were newly diagnosed with cancer in the period of the first lockdown from March 2020 to April 2020 and the second lockdown from November 2020 to December 2020 and compared to the same period in 2019. Results Our results showed a strong decline in newly diagnosed cancers during the lockdown periods: −45% in gynecological cancer and -52% in breast cancer compared to the same period in 2019. Compared to the analogue period of 2019, breast cancer patients reported significantly more tumor-associated symptoms (55% vs. 31%, p  = 0.013) during and in between (48% vs. 32%, p  = 0.022) the lockdowns. During the lockdown, periods in the group of breast cancer patients’ tumor stage varied significantly compared to 2019 (T2–T4; p  = 0.047). Conclusion Both lockdowns led to a strong decrease in newly diagnosed gynecological and breast cancers. Treatment delays in potentially curable disease could lead to inferior clinical outcomes, with the risk of missing the optimal treatment window. As the COVID-19 pandemic will be a challenge for some time to come, new strategies in patient care are needed to optimize cancer screening and management during the pandemic.
    Type of Medium: Online Resource
    ISSN: 1432-0711
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1458450-5
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  • 10
    In: Journal of Allergy and Clinical Immunology, Elsevier BV, Vol. 135, No. 5 ( 2015-05), p. 1207-1217.e11
    Type of Medium: Online Resource
    ISSN: 0091-6749
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 2006613-2
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