19 results on '"Kainz, Verena"'
Search Results
2. Lipedema: The Use of Cultured Adipocytes for Identification of Diagnostic Markers
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Ernst, Anna M., Steiner, Marianne, Kainz, Verena, Tempfer, Herbert, Spitzer, Gabriel, Plank, Tanja, Bauer, Hans-Christian, Bresgen, Nikolaus, Habenbacher, Andreas, Bauer, Hannelore, and Lipp, Anna-Theresa
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- 2023
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3. Coupling of a Major Allergen to the Surface of Immune Cells for Use in Prophylactic Cell Therapy for the Prevention of IgE-Mediated Allergy
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Mengrelis, Konstantinos, primary, Niederacher, Gerhard, additional, Prickler, Lisa, additional, Kainz, Verena, additional, Weijler, Anna Marianne, additional, Rudolph, Elisa, additional, Stanek, Victoria, additional, Eckl-Dorna, Julia, additional, Baranyi, Ulrike, additional, Spittler, Andreas, additional, Focke-Tejkl, Margarete, additional, Bohle, Barbara, additional, Valenta, Rudolf, additional, Becker, Christian Friedrich Wilhelm, additional, Wekerle, Thomas, additional, and Linhart, Birgit, additional
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- 2024
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4. Adoptive Cell Therapy in Mice Sensitized to a Grass Pollen Allergen.
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Weijler, Anna Marianne, Prickler, Lisa, Kainz, Verena, Bergmann, Eva, Bohle, Barbara, Regele, Heinz, Valenta, Rudolf, Linhart, Birgit, and Wekerle, Thomas
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CELLULAR therapy ,ALLERGENS ,POLLEN ,SKIN grafting ,MICE - Abstract
The proportion of patients with type I allergy in the world population has been increasing and with it the number of people suffering from allergic symptoms. Recently we showed that prophylactic cell therapy employing allergen-expressing bone marrow (BM) cells or splenic B cells induced allergen-specific tolerance in naïve mice. Here we investigated if cell therapy can modulate an established secondary allergen-specific immune response in pre-immunized mice. We sensitized mice against the grass pollen allergen Phl p 5 and an unrelated control allergen, Bet v 1, from birch pollen before the transfer of Phl p 5-expressing BM cells. Mice were conditioned with several combinations of low-dose irradiation, costimulation blockade, rapamycin and T cell-depleting anti-thymocyte globulin (ATG). Levels of allergen-specific IgE and IgG1 in serum after cell transfer were measured via ELISA and alterations in cellular responses were measured via an in vitro proliferation assay and transplantation of Phl p 5
+ skin grafts. None of the tested treatment protocols impacted Phl p 5-specific antibody levels. Transient low-level chimerism of Phl p 5+ leukocytes as well as a markedly prolonged skin graft survival were observed in mice conditioned with high numbers of Phl p 5+ BMC or no sensitization events between the day of cell therapy and skin grafting. The data presented herein demonstrate that a pre-existing secondary allergen-specific immune response poses a substantial hurdle opposing tolerization through cell therapy and underscore the importance of prophylactic approaches for the prevention of IgE-mediated allergy. [ABSTRACT FROM AUTHOR]- Published
- 2024
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5. Adoptive transfer of allergen-expressing B cells prevents IgE-mediated allergy
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Prickler, Lisa, primary, Baranyi, Ulrike, additional, Mengrelis, Konstantinos, additional, Weijler, Anna Marianne, additional, Kainz, Verena, additional, Kratzer, Bernhard, additional, Steiner, Romy, additional, Mucha, Jasmin, additional, Rudoph, Elisa, additional, Pilat, Nina, additional, Bohle, Barbara, additional, Strobl, Herbert, additional, Pickl, Winfried Franz, additional, Valenta, Rudolf, additional, Linhart, Birgit, additional, and Wekerle, Thomas, additional
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- 2023
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6. Epidermal growth factor receptor T790M Mutation Testing in Non-small Cell Lung Cancer: An International Collaborative Study to Assess Molecular EGFR T790M Testing in Liquid Biopsy
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Filipits, Martin, primary, Kainz, Verena, additional, Sebek, Viktor, additional, and Zach, Herwig, additional
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- 2023
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7. Adoptive transfer of allergenexpressing B cells prevents IgE-mediated allergy.
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Prickler, Lisa, Baranyi, Ulrike, Mengrelis, Konstantinos, Weijler, Anna Marianne, Kainz, Verena, Kratzer, Bernhard, Steiner, Romy, Mucha, Jasmin, Rudoph, Elisa, Pilat, Nina, Bohle, Barbara, Strobl, Herbert, Pickl, Winfried Franz, Valenta, Rudolf, Linhart, Birgit, and Wekerle, Thomas
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B cells ,HEMATOPOIETIC stem cells ,SKIN tests ,ALLERGIC rhinitis ,T cells - Abstract
Introduction: Prophylactic strategies to prevent the development of allergies by establishing tolerance remain an unmet medical need. We previously reported that the transfer of autologous hematopoietic stem cells (HSC) expressing the major timothy grass pollen allergen, Phl p 5, on their cell surface induced allergen-specific tolerance in mice. In this study, we investigated the ability of allergen-expressing immune cells (dendritic cells, CD4
+ T cells, CD8+ T cells, and CD19+ B cells) to induce allergen-specific tolerance in naive mice and identified CD19+ B cells as promising candidates for allergen-specific cell therapy. Methods: For this purpose, CD19+ B cells were isolated from Phl p 5-transgenic BALB/c mice and transferred to naive BALB/c mice, pre-treated with a short course of rapamycin and an anti-CD40L antibody. Subsequently, the mice were subcutaneously sensitized three times at 4-week intervals to Phl p 5 and Bet v 1 as an unrelated control allergen. Allergen-expressing cells were followed in the blood to monitor molecular chimerism, and sera were analyzed for Phl p 5- and Bet v 1-specific IgE and IgG1 levels by RBL assay and ELISA, respectively. In vivo allergen-induced lung inflammation was measured by whole-body plethysmography, and mast cell degranulation was determined by skin testing. Results: The transfer of purified Phl p 5-expressing CD19+ B cells to naive BALB/c mice induced B cell chimerism for up to three months and prevented the development of Phl p 5-specific IgE and IgG1 antibody responses for a follow-up period of 26 weeks. Since Bet v 1 but not Phl p 5-specific antibodies were detected, the induction of tolerance was specific for Phl p 5. Whole-body plethysmography revealed preserved lung function in CD19+ B cell-treated mice in contrast to sensitized mice, and there was no Phl p 5-induced mast cell degranulation in treated mice. Discussion: Thus, we demonstrated that the transfer of Phl p 5-expressing CD19+ B cells induces allergen-specific tolerance in a mouse model of grass pollen allergy. This approach could be further translated into a prophylactic regimen for the prevention of IgE-mediated allergy in humans. [ABSTRACT FROM AUTHOR]- Published
- 2023
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8. Figure S1 from The OncoMasTR Test Predicts Distant Recurrence in Estrogen Receptor–Positive, HER2-Negative Early-Stage Breast Cancer: A Validation Study in ABCSG Trial 8
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Filipits, Martin, primary, Rudas, Margaretha, primary, Kainz, Verena, primary, Singer, Christian F., primary, Fitzal, Florian, primary, Bago-Horvath, Zsuzsanna, primary, Greil, Richard, primary, Balic, Marija, primary, Regitnig, Peter, primary, Halper, Stefan, primary, Hulla, Wolfgang, primary, Egle, Daniel, primary, Barron, Stephen, primary, Loughman, Tony, primary, O'Leary, Des, primary, Gallagher, William M., primary, Hlauschek, Dominik, primary, Gnant, Michael, primary, and Dubsky, Peter, primary
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- 2023
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9. Optimum timing of antithymocyte globulin in relation to adoptive regulatory T cell therapy
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Muckenhuber, Moritz, primary, Mucha, Jasmin, additional, Mengrelis, Konstantinos, additional, How, Christopher, additional, Reindl-Schwaighofer, Roman, additional, Heinzel, Andreas, additional, Kainz, Verena, additional, Worel, Nina, additional, Berlakovich, Gabriela, additional, Edinger, Matthias, additional, Oberbauer, Rainer, additional, and Wekerle, Thomas, additional
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- 2023
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10. Epidermal Growth Factor Receptor T790M Mutation Testing in Non-Small Cell Lung Cancer: An International Collaborative Study to Assess Molecular EGFR T790M Testing in Liquid Biopsy.
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Filipits, Martin, Kainz, Verena, Sebek, Viktor, and Zach, Herwig
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LUNG cancer , *PROFESSIONAL practice , *GENETIC mutation , *BIOPSY , *SEQUENCE analysis , *EPIDERMAL growth factor receptors , *MOLECULAR pathology , *LABORATORIES , *BLOOD collection , *PROTEIN-tyrosine kinase inhibitors , *INTERPROFESSIONAL relations , *GENES , *SENSITIVITY & specificity (Statistics) , *POLYMERASE chain reaction ,BODY fluid examination - Abstract
Simple Summary: Several liquid biopsy platforms with varying degrees of accuracy are available for EGFR mutation testing in NSCLC. We performed a collaborative study to describe and compare the sensitivity of different liquid biopsy platforms used in clinical routines to detect selected EGFR mutations. In-house PCR-based and NGS-based methods were used accordingly, and results were reported as in routine clinical practice. The results might offer an essential contribution to ensuring high-quality standards and contribute to developing a standard EGFR T790M testing in liquid biopsy. Background: The detection of the EGFR T790M (T790M) mutation in non-small cell lung cancer (NSCLC) patients who progressed under treatment with first- or second-generation EGFR-tyrosine kinase inhibitors (TKIs) is important to offer a subsequent therapy with a third-generation EGFR-TKI. Liquid biopsy is a powerful tool to determine the T790M mutation status. Several liquid biopsy platforms with varying degrees of accuracy are available to test for T790M mutations, and sensitivities may differ among these methods. Methods: As no standard exists for the testing of T790M mutation in liquid biopsy, we performed a collaborative study to describe and compare the sensitivity of different in-house liquid biopsy platforms for the detection of the T790M mutation, EGFR exon 19 deletion (del19) and EGFR L858R mutation (L858R) across multiple participating laboratories in seven Central and Eastern European countries. Results: Of the 25 invited laboratories across Central and Eastern Europe, 21 centers participated and received 10 plasma samples spiked with cell-line DNA containing the T790M, del19, or L858R mutation in different concentrations. In-house PCR-based and NGS-based methods were used accordingly, and results were reported as in routine clinical practice. Two laboratories, which used the AmoyDx® EGFR 29 Mutations Detection Kit (AmoyDx) with Cobas® cfDNA Sample Preparation Kit and QX200 Droplet Digital PCR (ddPCR) with the QIAamp Circulating Nucleic Acid Kit identified all ten samples correctly. Cobas® EGFR Mutation Test v2 (Cobas), the NGS methods, and the IdyllaTM detection method used in this study performed within the known sensitivity range of each detection method. Conclusions: If a negative result was obtained from methods with lower sensitivity (e.g., Cobas), repeated liquid biopsy testing and/or tissue biopsy analysis should be performed whenever possible, to identify T790M-positive patients to allow them to receive the optimal second-line treatment with a third-generation EGFR TKI. [ABSTRACT FROM AUTHOR]
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- 2023
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11. The OncoMasTR Test Predicts Distant Recurrence in Estrogen Receptor–Positive, HER2-Negative Early-Stage Breast Cancer: A Validation Study in ABCSG Trial 8
- Author
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Filipits, Martin, primary, Rudas, Margaretha, additional, Kainz, Verena, additional, Singer, Christian F., additional, Fitzal, Florian, additional, Bago-Horvath, Zsuzsanna, additional, Greil, Richard, additional, Balic, Marija, additional, Regitnig, Peter, additional, Halper, Stefan, additional, Hulla, Wolfgang, additional, Egle, Daniel, additional, Barron, Stephen, additional, Loughman, Tony, additional, O'Leary, Des, additional, Gallagher, William M., additional, Hlauschek, Dominik, additional, Gnant, Michael, additional, and Dubsky, Peter, additional
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- 2021
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12. Detektion von MAPK Pathway Aktivierungen in juvenilen pilozytischen Astrozytomen als Teil der neuropatholgischen Diagnose
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Kainz, Verena
- Subjects
Molecular pathology ,MAP-Kinase ,Molekularpathologie ,MAPK Pathway ,Low-grade glioma ,Pilozytisches Astrozytom ,Zentralnervensystem ,Spongioblastom ,Niedriggradiges Gliom ,Pilocytic astrocytoma ,KIAA1549-BRAF - Abstract
Tumore des zentralen Nervensystems umfassen etwa 25 % aller neoplastischen Krankheiten bei Kindern, wobei das pilozytische Astrozytom der häufigste Gehirntumor ist. Pilozytische Astrozytome sind niedriggradige Gliome und entsprechen WHO Grad I. Es ist ein gutartiger und langsam wachsender Tumor, welcher bei vollständig operativer Entfernung günstige Prognosen aufweist. Obwohl dieser Tumortyp mit sehr gutem Gesamtüberleben assoziiert ist, besteht bei Kindern aufgrund von Rezidiven und bösartigem Verlauf trotz optimaler Resektion ein gewisses Sterblichkeitsrisiko. Konstitutive Aktivierung des MAP-Kinase (MAPK)-Pathway fördert die Bildung der meisten niedriggradigen Gliome und genetische Defekte wie KIAA1549-BRAF Fusionen und BRAF Mutationen sind dafür verantwortlich. Der häufigste Mechanismus der Aktivierung des MAPK-Pathways ist eine Tandemduplikation des Locus 7q34 und daraus resultierend die Entstehung des KIAA1549-BRAF Fusionstranskripts. Die Identifizierung dieses Transkripts ist von diagnostischer und prognostischer Bedeutung und eröffnet eventuell neue therapeutische Strategien für Patienten mit pilozytischen Astrozytomen. Es wurden 48 Patienten mit dokumentierten pilozytischen Astrozytomen untersucht. DNA und RNA wurden aus Formalin fixiertem und in Paraffin eingebettetem Gewebe und aus korrespondierendem Gefriermaterial isoliert. Polymerase-Kettenreaktion (PCR), Sequenzierung und „Multiplex ligation-dependent probe amplification“ (MLPA) wurden zur Detektion der Fusionen verwendet. Im Gefriermaterial konnten Fusionstranskripte in 38/48 Tumoren festgestellt werden wobei mittels Sequenzierung die KIAA1549-BRAF Fusionen 16-9 (24 Fälle), 15-9 (7 Fälle), 16-11 (6 Fälle) und 18-9 (1 Fall) bestätigt wurden. Die Detektion der Fusionen aus Formalin fixiertem Gewebe wurde bei 26 Proben durchgeführt. In keiner der untersuchten FFPE Gewebeproben konnte keine oder eine bestimmte Fusion mit Sicherheit bestimmt werden. Weiters wurde DNA von 35 Patienten isoliert und mittels MLPA auf die Tandemduplikation des Locus 7q34 analysiert. Vergleiche der Resultate aus der RT-PCR und der MLPA-Analyse zeigten, dass in 9 von 22 Fällen mit einem DQ zwischen 0,8 und 1,2 keine Fusion mittels RT-PCR gefunden wurde, während in den anderen 13 Fällen eine Fusion nachweisbar war. In allen Fällen bei denen der DQ zwischen 1,21 und 1,29 lag konnte mit der RT-PCR eine Fusion nachgewiesen werden. In einem von 6 Fällen bei denen der DQ zwischen 1,30 und 1,65 lag konnte keine Fusion nachgewiesen werden während bei den anderen 5 Fällen eine Fusion detektiert werden konnte. Zusammenfassend lässt sich feststellen, dass wir keine klaren und überzeugenden Ergebnisse für das Vorliegen der Tandemduplikation erhalten haben sowohl im Gefriermaterial als auch im FFPE-Gewebe. Da die Paraffinblöcke dieser Studie mindestens ein Jahr bei Raumtemperatur gelagert wurden und auch die Zeit der Fixierung in Formalin nicht genau dokumentiert wurde, benötigen wir weitere Untersuchungen um den Einfluss von Lagerung und Fixationszeit auf die Qualität von RNS und DNS, die aus Paraffinblöcken isoliert werden, zu untersuchen. Central nervous system tumors represent about 25 % of neoplastic disease in childhood and the pilocytic astrocytoma is the most frequent brain tumor in the pediatric population. Pilocytic astrocytomas are low-grade gliomas (LGG) and classified as WHO grade I. They are relative benign, slow growing tumors and can be cured due to surgery. Although this type of tumor is associated with excellent overall survival, children can suffer mortality due to recurrence and malignant progression even in the setting of optimal resection. Constitutive activation of the mitogen-activated protein kinase (MAPK) pathway drives the formation of the majority of LGGs and genetic defects including KIAA1549-BRAF fusions and BRAF mutations are responsible for it. The most common mechanism of MAPK pathway activation in LGGs is a tandem duplication in 7q34, resulting in a KIAA1549-BRAF fusion transcript. The identification of this fusion gene can be of diagnostic and prognostic value. The activation of the MAPK signaling pathway may open new therapeutic strategies for patients with pilocytic astrocytoma and so the detection of the gene fusions is important. 48 patients with well-documented pilocytic astrocytomas were examined. DNA and RNA were isolated from formalin-fixed, paraffin-embedded (FFPE) and corresponding frozen tumor samples. Polymerase chain reaction (PCR), sequencing and multiplex ligation-dependent probe amplification (MLPA) were used for the detection of the fusion transcripts. Fusion transcripts were detected in 38/48 tumors from frozen tissue. KIAA1549-BRAF gene fusions confirmed by sequencing included 16-9 (24 cases), 15-9 (7 cases), 16-11 (6 cases) and 18-9 (1 case). The detection of the fusion genes from FFPE tissue was performed from 26 tumor samples. In none of these FFPE tissue samples we could determine with certainty any particular fusion or no fusion at all. Furthermore, DNA from 35 patients was isolated to detect a 2 Megabase tandem duplication at 7q34 leading to KIAA1549-BRAF fusion using MLPA analysis. Comparing the results obtained from RT-PCR analysis and MLPA analysis we observed that in 9 out of 22 cases with a DQ between 0,8 and 1,2 no KIAA1549-BRAF fusion could be detected using RT-PCR, whereas in the remaining 13 cases the KIAA1549-BRAF fusion was found. In all cases with a DQ between 1,21 and 1,29 the KIAA1549-BRAF fusion could be detected using RT-PCR. In one out of 6 cases with a DQ between 1,30 and 1,65 no KIAA1549-BRAF fusion could be detected using RT-PCR, whereas in the remaining 5 cases the KIAA1549-BRAF fusion was found. Taken together, we were not able to obtain clear and convincing results for the presence of a 2 Megabase tandem duplication at 7q34 in FFPE tissues as well as fresh frozen tissues. Since FFPE tissue with a storage time for at least one year at room temperature was used and since the time between the sample collection and the fixation are no longer transparent it needs further investigations to examine the influence of storage time and fixation on the quality of RNA and DNA isolated from FFPE tissue samples. vorgelegt von: Verena Kainz Wien, FH Campus Wien, Masterarb., 2018
- Published
- 2018
13. Frontiers in Physiology / Phosphorylation of BK channels modulates the sensitivity to hydrogensulfide (H2S)
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Sitdikova, Guzel F., Fuchs, Roman, Kainz, Verena, Weiger, Thomas, and Hermann, Anton
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gasotransmitters ,hydrogensulfide (H2S) ,phosphorylation ,maxicalcium-activated potassium (BK) channels ,GH cells ,equipment and supplies ,patch clamp - Abstract
Introduction: Gases, such as nitric oxide (NO), carbon monoxide (CO), or hydrogen sulfide (H2S), termed gasotransmitters, play an increasingly important role in understanding of how electrical signaling of cells is modulated. H2S is well-known to act on various ion channels and receptors. In a previous study we reported that H2S increased calcium-activated potassium (BK) channel activity. Aims: The goal of the present study is to investigate the modulatory effect of BK channel phosphorylation on the action of H2S on the channel as well as to recalculate and determine the H2S concentrations in aqueous sodium hydrogen sulfide (NaHS) solutions. Methods: Single channel recordings of GH3, GH4, and GH4 STREX cells were used to analyze channel open probability, amplitude, and open dwell times. H2S was measured with an anion selective electrode. Results: The concentration of H2S produced from NaHS was recalculated taking pH, temperature salinity of the perfusate, and evaporation of H2S into account. The results indicate that from a concentration of 300 M NaHS, only 1113%, i.e., 3441 M is effective as H2S in solution. GH3, GH4, and GH4 STREX cells respond differently to phosphorylation. BK channel open probability (Po) of all cells lines used was increased by H2S in ATP-containing solutions. PKA prevented the action of H2S on channel Po in GH4 and GH4 STREX, but not in GH3 cells. H2S, high significantly increased Po of all PKG pretreated cells. In the presence of PKC, which lowers channel activity, H2S increased channel Po of GH4 and GH4 STREX, but not those of GH3 cells. H2S increased open dwell times of GH3 cells in the absence of ATP significantly. A significant increase of dwell times with H2S was also observed in the presence of okadaic acid. Conclusions: Our results suggest that phosphorylation by PKG primes the channels for H2S activation and indicate that channel phosphorylation plays an important role in the response to H2S. Guzel F. Sitdikova, Roman Fuchs, Verena Kainz, Thomas M. Weiger and Anton Hermann
- Published
- 2014
14. Phosphorylation of BK channels modulates the sensitivity to hydrogen sulfide (H2S)
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Sitdikova, Guzel F., primary, Fuchs, Roman, additional, Kainz, Verena, additional, Weiger, Thomas M., additional, and Hermann, Anton, additional
- Published
- 2014
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15. Phosphorylation of BK channels modulates the sensitivity to hydrogen sulfide (H2S).
- Author
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Sitdikova, Guzel F., Fuchs, Roman, Kainz, Verena, Weiger, Thomas M., and Hermann, Anton
- Subjects
CALCIUM-dependent potassium channels ,NITRIC oxide ,CARBON monoxide ,HYDROGEN sulfide ,PHOSPHORYLATION - Abstract
Introduction: Gases, such as nitric oxide (NO), carbon monoxide (CO), or hydrogen sulfide (H
2 S), termed gasotransmitters, play an increasingly important role in understanding of how electrical signaling of cells is modulated. H2 S is well-known to act on various ion channels and receptors. In a previous study we reported that H2 S increased calcium-activated potassium (BK) channel activity. Aims: The goal of the present study is to investigate the modulatory effect of BK channel phosphorylation on the action of H2 S on the channel as well as to recalculate and determine the H2 S concentrations in aqueous sodium hydrogen sulfide (NaHS) solutions. Methods: Single channel recordings of GH3, GH4, and GH4 STREX cells were used to analyze channel open probability, amplitude, and open dwell times. H2 S was measured with an anion selective electrode. Results: The concentration of H2 S produced from NaHS was recalculated taking pH, temperature salinity of the perfusate, and evaporation of H2 S into account. The results indicate that from a concentration of 300μM NaHS, only 11-13%, i.e., 34-41μM is effective as H2 S in solution. GH3, GH4, and GH4 STREX cells respond differently to phosphorylation. BK channel open probability (Po) of all cells lines used was increased by H2 S in ATP-containing solutions. PKA prevented the action of H2 S on channel Po in GH4 and GH4 STREX, but not in GH3 cells. H2 S, high significantly increased Po of all PKG pretreated cells. In the presence of PKC, which lowers channel activity, H2 S increased channel Po of GH4 and GH4 STREX, but not those of GH3 cells. H2 S increased open dwell times of GH3 cells in the absence of ATP significantly. A significant increase of dwell times with H2 S was also observed in the presence of okadaic acid. Conclusions: Our results suggest that phosphorylation by PKG primes the channels for H2 S activation and indicate that channel phosphorylation plays an important role in the response to H2 S. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
16. Antiproliferative Properties of Padma Lax and Its Components Ginger and Elecampane
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Hofbauer, Sebastian, primary, Kainz, Verena, additional, Golser, Leopold, additional, Klappacher, Michaela, additional, Kiesslich, Tobias, additional, Heidegger, Wilhelm, additional, Krammer, Barbara, additional, Hermann, Anton, additional, and Weiger, Thomas M., additional
- Published
- 2006
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17. Sarcoplasmic calcium-binding protein-immunoreactive material in the central nervous system of the snail, Helix pomatia
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Kerschbaum, Hubert H., primary, Kainz, Verena, additional, and Hermann, Anton, additional
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- 1992
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18. Nick translation of DNA immobilized on nylon membranes
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Kainz, Peter, primary and Kainz, Verena, additional
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- 1989
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19. Antiproliferative properties of Padma Lax and its components ginger and elecampane.
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Hofbauer S, Kainz V, Golser L, Klappacher M, Kiesslich T, Heidegger W, Krammer B, Hermann A, and Weiger TM
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- Cells, Cultured, Constipation complications, Dose-Response Relationship, Drug, Drug Synergism, Ethanol, Zingiber officinale, Humans, Intestinal Neoplasms etiology, Intestinal Neoplasms prevention & control, Time Factors, Cell Division drug effects, Constipation drug therapy, Medicine, Tibetan Traditional methods, Phytotherapy, Plant Extracts pharmacology
- Abstract
Background: Padma Lax (PL) is a multi-component herbal laxative, derived from traditional Tibetan medicine. It has been used in the treatment of constipation dominant irritable bowel syndrome. Beyond its purgative and bowel-regulating properties we found it to exhibit antiproliferative properties., Materials and Methods: C6 tumor cells were incubated with either an ethanolic or aqueous extract of PL. Cell proliferation, cell cycle, percentage of apoptotic cells, caspase-3/-7 activity as well as mitochondrial membrane potential were determined., Results: Ethanolic extracts of PL inhibited cell proliferation in a dose- and time-dependent manner (half max concentration: 384.4 mug/ml after 48 h of incubation). Aqueous extracts were less effective. Ginger and elecampane were the active components of PL in respect to its antiproliferative action and were found to act synergistically. Supplementing the culture medium with polyamines could not override the cytostatic action of PL. Incubation of C6 cells with PL in the presence of catalase proved that the PL effect was specific and not due to oxidative stress. PL had no effects on the cell cycle at a low dose but arrested cells in G1 at high concentrations. Reduction of cell numbers was found to be due to apoptosis. The caspase- 3/-7 pathway was not involved in the PL-induced cell death. However, mitochondrial membrane potential was lost during the course of incubation with PL indicating a mitochondrial- but not caspase-mediated induction of apoptosis., Conclusion: PL exhibits antiproliferative properties which may be beneficial to prevent constipation-related cancer. This study may also contribute to a future development of a new herbal-based antiproliferative treatment.
- Published
- 2006
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