13003
2012
eng
e47472
10
7
article
1
2016-03-16
--
--
Virotherapy of Canine Tumors with Oncolytic Vaccinia Virus GLV-1h109 Expressing an Anti-VEGF Single-Chain Antibody
Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for cancer therapy. We have previously reported that oncolytic vaccinia virus strains expressing an anti-VEGF (Vascular Endothelial Growth Factor) single-chain antibody (scAb) GLAF-1 exhibited significant therapeutic efficacy for treatment of human tumor xenografts. Here, we describe the use of oncolytic vaccinia virus GLV-1h109 encoding GLAF-1 for canine cancer therapy. In this study we analyzed the virus-mediated delivery and production of scAb GLAF-1 and the oncolytic and immunological effects of the GLV-1h109 vaccinia virus strain against canine soft tissue sarcoma and canine prostate carcinoma in xenograft models. Cell culture data demonstrated that the GLV-1h109 virus efficiently infect, replicate in and destroy both tested canine cancer cell lines. In addition, successful expression of GLAF-1 was demonstrated in virus-infected canine cancer cells and the antibody specifically recognized canine VEGF. In two different xenograft models, the systemic administration of the GLV-1h109 virus was found to be safe and led to anti-tumor and immunological effects resulting in the significant reduction of tumor growth in comparison to untreated control mice. Furthermore, tumor-specific virus infection led to a continued production of functional scAb GLAF-1, resulting in inhibition of angiogenesis. Overall, the GLV-1h109-mediated cancer therapy and production of immunotherapeutic anti-VEGF scAb may open the way for combination therapy concept i.e. vaccinia virus mediated oncolysis and intratumoral production of therapeutic drugs in canine cancer patients.
PLoS One
10.1371/journal.pone.0047472
urn:nbn:de:bvb:20-opus-130039
PLoS ONE 7(10): e47472. doi:10.1371/journal.pone.0047472
Sandeep S. Patil
Ivaylo Gentschev
Marion Adelfinger
Ulrike Donat
Michael Hess
Stephanie Weibel
Ingo Nolte
Alexa Frentzen
Aladar A. Szalay
eng
uncontrolled
angiogenesis
eng
uncontrolled
microenvironment
eng
uncontrolled
model
eng
uncontrolled
cancer
eng
uncontrolled
therapy
eng
uncontrolled
pet dogs
eng
uncontrolled
nude-mice
eng
uncontrolled
breast-tumors
eng
uncontrolled
microvascular density
eng
uncontrolled
endothelial growth-factor
Medizin und Gesundheit
open_access
Rudolf-Virchow-Zentrum
Lehrstuhl für Biochemie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13003/journal.pone.0047472.pdf
5762
2011
eng
article
1
2012-04-13
--
--
Viral-mediated oncolysis is the most critical factor in the late-phase of the tumor regression process upon vaccinia virus infection
Background: In principle, the elimination of malignancies by oncolytic virotherapy could proceed by different mechanisms - e.g. tumor cell specific oncolysis, destruction of the tumor vasculature or an anti-tumoral immunological response. In this study, we analyzed the contribution of these factors to elucidate the responsible mechanism for regression of human breast tumor xenografts upon colonization with an attenuated vaccinia virus (VACV). Methods: Breast tumor xenografts were analyzed 6 weeks post VACV infection (p.i.; regression phase) by immunohistochemistry and mouse-specific expression arrays. Viral-mediated oncolysis was determined by tumor growth analysis combined with microscopic studies of intratumoral virus distribution. The tumor vasculature was morphologically characterized by diameter and density measurements and vessel functionality was analyzed by lectin perfusion and extravasation studies. Immunological aspects of viral-mediated tumor regression were studied in either immune-deficient mouse strains (T-, B-, NK-cell-deficient) or upon cyclophosphamide-induced immunosuppression (MHCII+-cell depletion) in nude mice. Results: Late stage VACV-infected breast tumors showed extensive necrosis, which was highly specific to cancer cells. The tumor vasculature in infected tumor areas remained functional and the endothelial cells were not infected. However, viral colonization triggers hyperpermeability and dilatation of the tumor vessels, which resembled the activated endothelium in wounded tissue. Moreover, we demonstrated an increased expression of genes involved in leukocyte-endothelial cell interaction in VACV-infected tumors, which orchestrate perivascular inflammatory cell infiltration. The immunohistochemical analysis of infected tumors displayed intense infiltration of MHCII-positive cells and colocalization of tumor vessels with MHCII+/CD31+ vascular leukocytes. However, GI-101A tumor growth analysis upon VACV-infection in either immunosuppressed nude mice (MHCII+-cell depleted) or in immune-deficient mouse strains (T-, B-, NK-cell-deficient) revealed that neither MHCII-positive immune cells nor T-, B-, or NK cells contributed significantly to VACV-mediated tumor regression. In contrast, tumors of immunosuppressed mice showed enhanced viral spreading and tumor necrosis. Conclusions: Taken together, these results indicate that VACV-mediated oncolysis is the primary mechanism of tumor shrinkage in the late regression phase. Neither the destruction of the tumor vasculature nor the massive VACV-mediated intratumoral inflammation was a prerequisite for tumor regression. We propose that approaches to enhance viral replication and spread within the tumor microenvironment should improve therapeutical outcome.
urn:nbn:de:bvb:20-opus-68691
6869
BMC Cancer (2011) 11, doi:10.1186/1471-2407-11-68
Stephanie Weibel
Viktoria Raab
Yong A. Yu
Andrea Worschech
Ena Wang
Francesco M. Marincola
Aladar A. Szalay
deu
swd
Virusinfektion
deu
swd
Krebs <Medizin>
Medizin und Gesundheit
open_access
Institut für Molekulare Infektionsbiologie
Förderzeitraum 2011
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5762/Szalay_1471_2407_11_68.pdf
14080
2012
eng
366
12
article
1
2016-11-25
--
--
Vaccinia virus-mediated intra-tumoral expression of matrix metalloproteinase 9 enhances oncolysis of PC-3 xenograft tumors
Background
Oncolytic viruses, including vaccinia virus (VACV), are a promising alternative to classical mono-cancer treatment methods such as surgery, chemo- or radiotherapy. However, combined therapeutic modalities may be more effective than mono-therapies. In this study, we enhanced the effectiveness of oncolytic virotherapy by matrix metalloproteinase (MMP-9)-mediated degradation of proteins of the tumoral extracellular matrix (ECM), leading to increased viral distribution within the tumors.
Methods
For this study, the oncolytic vaccinia virus GLV-1h255, containing the mmp-9 gene, was constructed and used to treat PC-3 tumor-bearing mice, achieving an intra-tumoral over-expression of MMP-9. The intra-tumoral MMP-9 content was quantified by immunohistochemistry in tumor sections. Therapeutic efficacy of GLV-1h255 was evaluated by monitoring tumor growth kinetics and intra-tumoral virus titers. Microenvironmental changes mediated by the intra-tumoral MMP-9 over-expression were investigated by microscopic quantification of the collagen IV content, the blood vessel density (BVD) and the analysis of lymph node metastasis formation.
Results
GLV-1h255-treatment of PC-3 tumors led to a significant over-expression of intra-tumoral MMP-9, accompanied by a marked decrease in collagen IV content in infected tumor areas, when compared to GLV-1h68-infected tumor areas. This led to considerably elevated virus titers in GLV-1h255 infected tumors, and to enhanced tumor regression. The analysis of the BVD, as well as the lumbar and renal lymph node volumes, revealed lower BVD and significantly smaller lymph nodes in both GLV-1h68- and GLV-1h255- injected mice compared to those injected with PBS, indicating that MMP-9 over-expression does not alter the metastasis-reducing effect of oncolytic VACV.
Conclusions
Taken together, these results indicate that a GLV-1h255-mediated intra-tumoral over-expression of MMP-9 leads to a degradation of collagen IV, facilitating intra-tumoral viral dissemination, and resulting in accelerated tumor regression. We propose that approaches which enhance the oncolytic effect by increasing the intra-tumoral viral load, may be an effective way to improve therapeutic outcome.
BMC Cancer
10.1186/1471-2407-12-366
urn:nbn:de:bvb:20-opus-140800
BMC Cancer 2012, 12:366. DOI:10.1186/1471-2407-12-366
Simon Schäfer
Stephanie Weibel
Ulrike Donat
Quian Zhang
Richard J. Aguilar
Nanhai G. Chen
Aladar A. Szalay
eng
uncontrolled
microenvironment
eng
uncontrolled
angiogenesis
eng
uncontrolled
therapy
eng
uncontrolled
cancer
eng
uncontrolled
breast-tumors
eng
uncontrolled
matrix metalloproteinases
eng
uncontrolled
adenovirus
eng
uncontrolled
carcinoma
eng
uncontrolled
prostate
eng
uncontrolled
mice
Medizin und Gesundheit
open_access
Lehrstuhl für Biochemie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14080/art_101186_1471-2407-12-366.pdf
6641
2012
eng
article
1
2013-06-04
--
--
Vaccinia virus-mediated intra-tumoral expression of matrix metalloproteinase 9 enhances oncolysis of PC-3 xenograft tumors
Background: Oncolytic viruses, including vaccinia virus (VACV), are a promising alternative to classical mono-cancer treatment methods such as surgery, chemo- or radiotherapy. However, combined therapeutic modalities may be more effective than mono-therapies. In this study, we enhanced the effectiveness of oncolytic virotherapy by matrix metalloproteinase (MMP-9)-mediated degradation of proteins of the tumoral extracellular matrix (ECM), leading to increased viral distribution within the tumors. Methods: For this study, the oncolytic vaccinia virus GLV-1h255, containing the mmp-9 gene, was constructed and used to treat PC-3 tumor-bearing mice, achieving an intra-tumoral over-expression of MMP-9. The intra-tumoral MMP-9 content was quantified by immunohistochemistry in tumor sections. Therapeutic efficacy of GLV-1h255 was evaluated by monitoring tumor growth kinetics and intra-tumoral virus titers. Microenvironmental changes mediated by the intra-tumoral MMP-9 over-expression were investigated by microscopic quantification of the collagen IV content, the blood vessel density (BVD) and the analysis of lymph node metastasis formation. Results: GLV-1h255-treatment of PC-3 tumors led to a significant over-expression of intra-tumoral MMP-9, accompanied by a marked decrease in collagen IV content in infected tumor areas, when compared to GLV-1h68-infected tumor areas. This led to considerably elevated virus titers in GLV-1h255 infected tumors, and to enhanced tumor regression. The analysis of the BVD, as well as the lumbar and renal lymph node volumes, revealed lower BVD and significantly smaller lymph nodes in both GLV-1h68- and GLV-1h255- injected mice compared to those injected with PBS, indicating that MMP-9 over-expression does not alter the metastasis-reducing effect of oncolytic VACV. Conclusions: Taken together, these results indicate that a GLV-1h255-mediated intra-tumoral over-expression of MMP-9 leads to a degradation of collagen IV, facilitating intra-tumoral viral dissemination, and resulting in accelerated tumor regression. We propose that approaches which enhance the oncolytic effect by increasing the intra-tumoral viral load, may be an effective way to improve therapeutic outcome.
urn:nbn:de:bvb:20-opus-78220
7822
In: BMC Cancer (2012) 12:366, doi:10.1186/1471-2407-12-366.
Simon Schäfer
Stephanie Weibel
Ulrike Donat
Qian Zhang
Richard J. Aguilar
Nanhai G. Chen
Aladar A. Szalay
deu
swd
Biochemie
Biowissenschaften; Biologie
open_access
Lehrstuhl für Biochemie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6641/088_1471_2407_12_366.pdf
26551
2021
eng
21
article
1
2022-04-04
--
--
Trial registration and selective outcome reporting in 585 clinical trials investigating drugs for prevention of postoperative nausea and vomiting
Background: Selective outcome reporting in clinical trials introduces bias in the body of evidence distorting clinical decision making. Trial registration aims to prevent this bias and is suggested by the International Committee of Medical Journal Editors (ICMJE) since 2004.
Methods: The 585 randomized controlled trials (RCTs) published between 1965 and 2017 that were included in a recently published Cochrane review on antiemetic drugs for prevention of postoperative nausea and vomiting were selected. In a retrospective study, we assessed trial registration and selective outcome reporting by comparing study publications with their registered protocols according to the ‘Cochrane Risk of bias’ assessment tool 1.0.
Results: In the Cochrane review, the first study which referred to a registered trial protocol was published in 2004. Of all 585 trials included in the Cochrane review, 334 RCTs were published in 2004 or later, of which only 22% (75/334) were registered. Among the registered trials, 36% (27/75) were pro- and 64% (48/75) were retrospectively registered. 41% (11/27) of the prospectively registered trials were free of selective outcome reporting bias, 22% (6/27) were incompletely registered and assessed as unclear risk, and 37% (10/27) were assessed as high risk. Major outcome discrepancies between registered and published high risk trials were a change from the registered primary to a published secondary outcome (32%), a new primary outcome (26%), and different outcome assessment times (26%). Among trials with high risk of selective outcome reporting 80% favoured at least one statistically significant result. Registered trials were assessed more often as ‘overall low risk of bias’ compared to non-registered trials (64% vs 28%).
Conclusions: In 2017, 13 years after the ICMJE declared prospective protocol registration a necessity for reliable clinical studies, the frequency and quality of trial registration in the field of PONV is very poor. Selective outcome reporting reduces trustworthiness in findings of clinical trials. Investigators and clinicians should be aware that only following a properly registered protocol and transparently reporting of predefined outcomes, regardless of the direction and significance of the result, will ultimately strengthen the body of evidence in the field of PONV research in the future.
BMC Anesthesiology
10.1186/s12871-021-01464-w
urn:nbn:de:bvb:20-opus-265518
publish
BMC Anesthesiology (2021) 21:249. https://doi.org/10.1186/s12871-021-01464-w
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Manuel Riemer
Peter Kranke
Antonia Helf
Debora Mayer
Maria Popp
Tobias Schlesinger
Patrick Meybohm
Stephanie Weibel
eng
uncontrolled
clinical trial
eng
uncontrolled
postoperative nausea and vomiting
eng
uncontrolled
selective outcome reporting
eng
uncontrolled
systematic review
eng
uncontrolled
trial registration
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Förderzeitraum 2021
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/26551/s12871-021-01464-w.pdf
9601
2013
eng
article
1
--
--
--
Treatment of malignant effusion by oncolytic virotherapy in an experimental subcutaneous xenograft model of lung cancer
Background
Malignant pleural effusion (MPE) is associated with advanced stages of lung cancer and is mainly dependent on invasion of the pleura and expression of vascular endothelial growth factor (VEGF) by cancer cells. As MPE indicates an incurable disease with limited palliative treatment options and poor outcome, there is an urgent need for new and efficient treatment options.
Methods
In this study, we used subcutaneously generated PC14PE6 lung adenocarcinoma xenografts in athymic mice that developed subcutaneous malignant effusions (ME) which mimic pleural effusions of the orthotopic model. Using this approach monitoring of therapeutic intervention was facilitated by direct observation of subcutaneous ME formation without the need of sacrificing mice or special imaging equipment as in case of MPE. Further, we tested oncolytic virotherapy using Vaccinia virus as a novel treatment modality against ME in this subcutaneous PC14PE6 xenograft model of advanced lung adenocarcinoma.
Results
We demonstrated significant therapeutic efficacy of Vaccinia virus treatment of both advanced lung adenocarcinoma and tumor-associated ME. We attribute the efficacy to the virus-mediated reduction of tumor cell-derived VEGF levels in tumors, decreased invasion of tumor cells into the peritumoral tissue, and to viral infection of the blood vessel-invading tumor cells. Moreover, we showed that the use of oncolytic Vaccinia virus encoding for a single-chain antibody (scAb) against VEGF (GLAF-1) significantly enhanced mono-therapy of oncolytic treatment.
Conclusions
Here, we demonstrate for the first time that oncolytic virotherapy using tumor-specific Vaccinia virus represents a novel and promising treatment modality for therapy of ME associated with advanced lung cancer.
Journal of Translational Medicine
doi:10.1186/1479-5876-11-106
http://www.translational-medicine.com/content/11/1/106
urn:nbn:de:bvb:20-opus-96016
MRB Forschungszentrum für Magnet-Resonanz-Bayern e.V., Am Hubland, D-97074 Würzburg
Genelux Corporation, San Diego Science Center, 3030 Bunker Hill Street, Suite 310, San Diego, California 92109, USA
In: Journal of Translational Medicine (2013) 11: 106, doi:10.1186/1479-5876-11-106
Aladar A Szalay
Stephanie Weibel
Elisabeth Hofmann
Thomas Christian Basse-Luesebrink
Ulrike Donat
Carolin Seubert
Marion Adelfinger
Prisca Gnamlin
Christina Kober
Alexa Frentzen
Ivaylo Gentschev
Peter Michael Jakob
eng
uncontrolled
Oncolytic virotherapy
eng
uncontrolled
Malignant effusion
eng
uncontrolled
Lung cancer
eng
uncontrolled
VEGF
deu
swd
Lungenkrebs
deu
swd
Vascular endothelial Growth Factor
Medizin und Gesundheit
open_access
Physikalisches Institut
Institut für Molekulare Infektionsbiologie
Rudolf-Virchow-Zentrum
Lehrstuhl für Biochemie
Förderzeitraum 2013
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/9601/Szalay_1479-5876-11-106.pdf
25228
2021
eng
1
11
article
1
--
2021-12-23
--
Safety and efficacy of intermediate- and therapeutic-dose anticoagulation for hospitalised patients with COVID-19: a systematic review and meta-analysis
Background: COVID-19 patients are at high thrombotic risk. The safety and efficacy of different anticoagulation regimens in COVID-19 patients remain unclear. Methods: We searched for randomised controlled trials (RCTs) comparing intermediate- or therapeutic-dose anticoagulation to standard thromboprophylaxis in hospitalised patients with COVID-19 irrespective of disease severity. To assess efficacy and safety, we meta-analysed data for all-cause mortality, clinical status, thrombotic event or death, and major bleedings. Results: Eight RCTs, including 5580 patients, were identified, with two comparing intermediate- and six therapeutic-dose anticoagulation to standard thromboprophylaxis. Intermediate-dose anticoagulation may have little or no effect on any thrombotic event or death (RR 1.03, 95% CI 0.86–1.24), but may increase major bleedings (RR 1.48, 95% CI 0.53–4.15) in moderate to severe COVID-19 patients. Therapeutic-dose anticoagulation may decrease any thrombotic event or death in patients with moderate COVID-19 (RR 0.64, 95% CI 0.38–1.07), but may have little or no effect in patients with severe disease (RR 0.98, 95% CI 0.86–1.12). The risk of major bleedings may increase independent of disease severity (RR 1.78, 95% CI 1.15–2.74). Conclusions: Certainty of evidence is still low. Moderately affected COVID-19 patients may benefit from therapeutic-dose anticoagulation, but the risk for bleeding is increased.
Journal of Clinical Medicine
2077-0383
10.3390/jcm11010057
urn:nbn:de:bvb:20-opus-252285
2022-01-03T15:38:43+00:00
sword
swordwue
attachment; filename=deposit.zip
b945a90342c1b9c67943029874e83b26
Journal of Clinical Medicine (2022) 11:1, 57. https://doi.org/10.3390/jcm11010057
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Stefanie Reis
Maria Popp
Benedikt Schmid
Miriam Stegemann
Maria-Inti Metzendorf
Peter Kranke
Patrick Meybohm
Stephanie Weibel
eng
uncontrolled
anticoagulant therapy
eng
uncontrolled
coronavirus disease 2019
eng
uncontrolled
thrombosis
eng
uncontrolled
bleeding
eng
uncontrolled
death
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/25228/jcm-11-00057.pdf
12999
2012
eng
5
7
article
1
2016-03-15
--
--
Preclinical Evaluation of Oncolytic Vaccinia Virus for Therapy of Canine Soft Tissue Sarcoma
Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for canine cancer therapy. In this study we describe the establishment of an in vivo model of canine soft tissue sarcoma (CSTS) using the new isolated cell line STSA-1 and the analysis of the virus-mediated oncolytic and immunological effects of two different Lister VACV LIVP1.1.1 and GLV-1h68 strains against CSTS. Cell culture data demonstrated that both tested VACV strains efficiently infected and destroyed cells of the canine soft tissue sarcoma line STSA-1. In addition, in our new canine sarcoma tumor xenograft mouse model, systemic administration of LIVP1.1.1 or GLV-1h68 viruses led to significant inhibition of tumor growth compared to control mice. Furthermore, LIVP1.1.1 mediated therapy resulted in almost complete tumor regression and resulted in long-term survival of sarcoma-bearing mice. The replication of the tested VACV strains in tumor tissues led to strong oncolytic effects accompanied by an intense intratumoral infiltration of host immune cells, mainly neutrophils. These findings suggest that the direct viral oncolysis of tumor cells and the virus-dependent activation of tumor-associated host immune cells could be crucial parts of anti-tumor mechanism in STSA-1 xenografts. In summary, the data showed that both tested vaccinia virus strains and especially LIVP1.1.1 have great potential for effective treatment of CSTS.
PLoS One
10.1371/journal.pone.0037239
urn:nbn:de:bvb:20-opus-129998
PLoS ONE 7(5): e37239. doi:10.1371/journal.pone.0037239
Ivaylo Gentschev
Marion Adelfinger
Rafael Josupeit
Stephan Rudolph
Klaas Ehrig
Ulrike Donat
Stephanie Weibel
Nanhai G. Chen
Yong A. Yu
Qian Zhang
Martin Heisig
Douglas Thamm
Jochen Stritzker
Amy MacNeill
Aladar A. Szalay
eng
uncontrolled
breast-tumors
eng
uncontrolled
animal-model
eng
uncontrolled
nude-mice
eng
uncontrolled
cell-line
eng
uncontrolled
in-vitro
eng
uncontrolled
glv-1h68
eng
uncontrolled
cancer
eng
uncontrolled
virotherapy
eng
uncontrolled
dogs
eng
uncontrolled
neutrophils
Medizin und Gesundheit
open_access
Institut für Medizinische Strahlenkunde und Zellforschung
Institut für Molekulare Infektionsbiologie
Rudolf-Virchow-Zentrum
Lehrstuhl für Biochemie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12999/journal.pone.0037239.pdf
12651
2015
eng
216
13
article
1
2016-01-31
--
--
Microglia and astrocytes attenuate the replication of the oncolytic vaccinia virus LIVP 1.1.1 in murine GL261 gliomas by acting as vaccinia virus traps
Background
Oncolytic virotherapy is a novel approach for the treatment of glioblastoma multiforme (GBM) which is still a fatal disease. Pathologic features of GBM are characterized by the infiltration with microglia/macrophages and a strong interaction between immune- and glioma cells. The aim of this study was to determine the role of microglia and astrocytes for oncolytic vaccinia virus (VACV) therapy of GBM.
Methods
VACV LIVP 1.1.1 replication in C57BL/6 and \(Foxn1^{nu/nu}\) mice with and without GL261 gliomas was analyzed. Furthermore, immunohistochemical analysis of microglia and astrocytes was investigated in non-, mock-, and LIVP 1.1.1-infected orthotopic GL261 gliomas in C57BL/6 mice. In cell culture studies virus replication and virus-mediated cell death of GL261 glioma cells was examined, as well as in BV-2 microglia and IMA2.1 astrocytes with M1 or M2 phenotypes. Co-culture experiments between BV-2 and GL261 cells and apoptosis/necrosis studies were performed. Organotypic slice cultures with implanted GL261 tumor spheres were used as additional cell culture system.
Results
We discovered that orthotopic GL261 gliomas upon intracranial virus delivery did not support replication of LIVP 1.1.1, similar to VACV-infected brains without gliomas. In addition, recruitment of \(Iba1^+\) microglia and \(GFAP^+\) astrocytes to orthotopically implanted GL261 glioma sites occurred already without virus injection. GL261 cells in culture showed high virus replication, while replication in BV-2 and IMA2.1 cells was barely detectable. The reduced viral replication in BV-2 cells might be due to rapid VACV-induced apoptotic cell death. In BV-2 and IMA 2.1 cells with M1 phenotype a further reduction of virus progeny and virus-mediated cell death was detected. Application of BV-2 microglial cells with M1 phenotype onto organotypic slice cultures with implanted GL261 gliomas resulted in reduced infection of BV-2 cells, whereas GL261 cells were well infected.
Conclusion
Our results indicate that microglia and astrocytes, dependent on their activation state, may preferentially clear viral particles by immediate uptake after delivery. By acting as VACV traps they further reduce efficient virus infection of the tumor cells. These findings demonstrate that glia cells need to be taken into account for successful GBM therapy development.
Journal of Translational Medicine
10.1186/s12967-015-0586-x
urn:nbn:de:bvb:20-opus-126517
Journal of Translational Medicine (2015) 13:216 DOI 10.1186/s12967-015-0586-x
Christina Kober
Susanne Rohn
Stephanie Weibel
Ulrike Geissinger
Nanhai G. Chen
Aladar A. Szalay
eng
uncontrolled
GBM
eng
uncontrolled
tumor microenvironment
eng
uncontrolled
microglia
eng
uncontrolled
polarization
eng
uncontrolled
VACV
eng
uncontrolled
OSC
eng
uncontrolled
IMA2.1
eng
uncontrolled
BV-2
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Rudolf-Virchow-Zentrum
Lehrstuhl für Biochemie
Förderzeitraum 2015
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12651/Szalay_s12967-015-0586-x.pdf
25828
2021
eng
1490–1496
10
65
article
1
--
--
--
Intraoperative management of combined general anesthesia and thoracic epidural analgesia: A survey among German anesthetists
Background
Evidence concerning combined general anesthesia (GA) and thoracic epidural analgesia (EA) is controversial and the procedure appears heterogeneous in clinical implementation. We aimed to gain an overview of different approaches and to unveil a suspected heterogeneity concerning the intraoperative management of combined GA and EA.
Methods
This was an anonymous survey among Members of the Scientific working group for regional anesthesia within the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) conducted from February 2020 to August 2020.
Results
The response rate was 38%. The majority of participants were experienced anesthetists with high expertise for the specific regimen of combined GA and EA. Most participants establish EA in the sitting position (94%), prefer early epidural initiation (prior to skin incision: 80%; intraoperative: 14%) and administer ropivacaine (89%) in rather low concentrations (0.2%: 45%; 0.375%: 30%; 0.75%: 15%) mostly with an opioid (84%) in a bolus-based mode (95%). The majority reduce systemic opioid doses intraoperatively if EA works sufficiently (minimal systemic opioids: 58%; analgesia exclusively via EA: 34%). About 85% manage intraoperative EA insufficiency with systemic opioids, 52% try to escalate EA, and only 25% use non-opioids, e.g. intravenous ketamine or lidocaine.
Conclusions
Although, consensus seems to be present for several aspects (patient's position during epidural puncture, main epidural substance, application mode), there is considerable heterogeneity regarding systemic opioids, rescue strategies for insufficient EA, and hemodynamic management, which might explain inconsistent results of previous trials and meta-analyses.
Acta Anaesthesiologica Scandinavica
10.1111/aas.13971
urn:nbn:de:bvb:20-opus-258286
publish
Acta Anaesthesiologica Scandinavica 2021, 65(10):1490–1496. DOI: 10.1111/aas.13971
false
true
CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International
Tobias Schlesinger
Stephanie Weibel
Thorsten Steinfeldt
Magdalena Sitter
Patrick Meybohm
Peter Kranke
eng
uncontrolled
analgesics
eng
uncontrolled
enhanced recovery after surgery
eng
uncontrolled
multimodal treatments
eng
uncontrolled
perioperative care
eng
uncontrolled
epidural analgesia
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/25828/Schlesinger_Acta.pdf
29966
2022
eng
1
11
article
1
--
--
--
Include or not to include conference abstracts in systematic reviews? Lessons learned from a large Cochrane network meta-analysis including 585 trials
Background
Systematic reviews attempt to gather all available evidence. Controversy exists regarding effort and benefit of including study results presented at conferences only. We recently published a Cochrane network meta-analysis (NMA) including 585 randomized controlled trials comparing drugs for prevention of postoperative nausea and vomiting (PONV). Studies published as conference abstracts only were excluded. This study aimed to include all eligible studies published as abstracts only, assessing their added value regarding reporting quality and effect on the review’s interpretation.
Methods
Conference abstracts were searched in the review’s excluded studies and conference proceedings of anaesthesiologic societies. We assessed their reporting quality regarding review’s eligibility criteria, Cochrane ‘risk of bias’ assessment tool 1.0, and adherence to CONSORT (Consolidated Standards of Reporting Trials) for abstracts. Abstracts were included in sensitivity NMA, and impact on the NMA structure was investigated.
Results
We identified 90 abstracts. A total of 14% (13/90) were eligible. A total of 86% (77/90) are awaiting classification due to insufficient reporting of review’s eligibility criteria. In abstracts awaiting classification, sufficient information was missing on standardization of anaesthesia in 71% (55/77), age of participants in 56% (43/77), and outcome details in 46% (36/77). A total of 73% (66/90) of abstracts lacked sufficient information on 15/25 data extraction items. Reported study characteristics of abstracts were comparable to included studies of the review. A total of 62% (56/90) of abstract trials were assessed as overall high risk of bias due to poor reporting. Median adherence to CONSORT for abstracts was 24% (IQR, 18 to 29%). Six of the 13 eligible abstracts reported relevant outcome data in sufficient detail for NMA on seven outcomes of the Cochrane review. Inclusion of abstracts did not substantially change the network structure, network effect estimates, ranking of treatments, or the conclusion. Certainty of evidence for headache on palonosetron use was upgraded from very low to low.
Conclusions
Most conference abstracts on PONV were insufficiently reported regarding review’s narrow inclusion criteria and could not be included in NMA. The resource-intensive search and evaluation of abstracts did not substantially extent the full-text evidence base of the review, given the few adequately reported abstracts. Conferences should oblige authors to adhere to CONSORT for abstracts.
Systematic Reviews
10.1186/s13643-022-02048-6
urn:nbn:de:bvb:20-opus-299660
@articleHackenbroich.2022, author = Hackenbroich, Samantha and Kranke, Peter and Meybohm, Patrick and Weibel, Stephanie, year = 2022, title = Include or not to include conference abstracts in systematic reviews? Lessons learned from a large Cochrane network meta-analysis including 585 trials, pages = 178, volume = 11, number = 1, journal = Systematic reviews, doi = 10.1186/s13643-022-02048-6,
md5:a4714214de6b331c4cf9b3d414283a12
2023-01-18T06:53:00+00:00
/tmp/phpNarr3J
bibtex
63c7974c388cf4.41120023
Systematic Reviews 2022, 11(1):178. DOI: 10.1186/s13643-022-02048-6
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Samantha Hackenbroich
Peter Kranke
Patrick Meybohm
Stephanie Weibel
eng
uncontrolled
systemic reviews
eng
uncontrolled
conference abstracts
eng
uncontrolled
meta-analysis
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/29966/Systematic_Hackenbroich.pdf
13031
2013
eng
e56317
3
8
article
1
2016-03-18
--
--
Imaging of Intratumoral Inflammation during Oncolytic Virotherapy of Tumors by \(^{19}\)F-Magnetic Resonance Imaging (MRI)
Background
Oncolytic virotherapy of tumors is an up-coming, promising therapeutic modality of cancer therapy. Unfortunately, non-invasive techniques to evaluate the inflammatory host response to treatment are rare. Here, we evaluate \(^{19}\)F magnetic resonance imaging (MRI) which enables the non-invasive visualization of inflammatory processes in pathological conditions by the use of perfluorocarbon nanoemulsions (PFC) for monitoring of oncolytic virotherapy.
Methodology/Principal Findings
The Vaccinia virus strain GLV-1h68 was used as an oncolytic agent for the treatment of different tumor models. Systemic application of PFC emulsions followed by \(^1H\)/\(^{19}\)F MRI of mock-infected and GLV-1h68-infected tumor-bearing mice revealed a significant accumulation of the \(^{19}\)F signal in the tumor rim of virus-treated mice. Histological examination of tumors confirmed a similar spatial distribution of the \(^{19}\)F signal hot spots and \(CD68^+\)-macrophages. Thereby, the \(CD68^+\)-macrophages encapsulate the GFP-positive viral infection foci. In multiple tumor models, we specifically visualized early inflammatory cell recruitment in Vaccinia virus colonized tumors. Furthermore, we documented that the \(^{19}\)F signal correlated with the extent of viral spreading within tumors.
Conclusions/Significance
These results suggest \(^{19}\)F MRI as a non-invasive methodology to document the tumor-associated host immune response as well as the extent of intratumoral viral replication. Thus, \(^{19}\)F MRI represents a new platform to non-invasively investigate the role of the host immune response for therapeutic outcome of oncolytic virotherapy and individual patient response.
PLoS ONE
10.1371/journal.pone.0056317
urn:nbn:de:bvb:20-opus-130311
PLoS ONE 8(2): e56317. doi:10.1371/journal.pone.0056317
Stephanie Weibel
Thomas Christian Basse-Luesebrink
Michael Hess
Elisabeth Hofmann
Carolin Seubert
Johanna Langbein-Laugwitz
Ivaylo Gentschev
Volker Jörg Friedrich Sturm
Yuxiang Ye
Thomas Kampf
Peter Michael Jakob
Aladar A. Szalay
eng
uncontrolled
inflammation
eng
uncontrolled
fluorescence microscopy
eng
uncontrolled
oncolytic viruses
eng
uncontrolled
fluorescence imaging
eng
uncontrolled
macrophages
eng
uncontrolled
magnetic resonance imaging
eng
uncontrolled
histology
eng
uncontrolled
in vivo imaging
Biochemie
open_access
Physikalisches Institut
Institut für Molekulare Infektionsbiologie
Rudolf-Virchow-Zentrum
Lehrstuhl für Biochemie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13031/104_Weibel_Imaging_of_Intratumoral.pdf
31823
2023
eng
357
369
3
14
article
1
--
--
--
Identifying and managing problematic trials: A research integrity assessment tool for randomized controlled trials in evidence synthesis
Evidence synthesis findings depend on the assumption that the included studies follow good clinical practice and results are not fabricated or false. Studies which are problematic due to scientific misconduct, poor research practice, or honest error may distort evidence synthesis findings. Authors of evidence synthesis need transparent mechanisms to identify and manage problematic studies to avoid misleading findings. As evidence synthesis authors of the Cochrane COVID-19 review on ivermectin, we identified many problematic studies in terms of research integrity and regulatory compliance. Through iterative discussion, we developed a research integrity assessment (RIA) tool for randomized controlled trials for the update of this Cochrane review. In this paper, we explain the rationale and application of the RIA tool in this case study. RIA assesses six study criteria: study retraction, prospective trial registration, adequate ethics approval, author group, plausibility of methods (e.g., randomization), and plausibility of study results. RIA was used in the Cochrane review as part of the eligibility check during screening of potentially eligible studies. Problematic studies were excluded and studies with open questions were held in awaiting classification until clarified. RIA decisions were made independently by two authors and reported transparently. Using the RIA tool resulted in the exclusion of >40% of studies in the first update of the review. RIA is a complementary tool prior to assessing “Risk of Bias” aiming to establish the integrity and authenticity of studies. RIA provides a platform for urgent development of a standard approach to identifying and managing problematic studies.
Research Synthesis Methods
10.1002/jrsm.1599
urn:nbn:de:bvb:20-opus-318236
@articleWeibel.2023, author = Weibel, Stephanie and Popp, Maria and Reis, Stefanie and Skoetz, Nicole and Garner, Paul and Sydenham, Emma, year = 2023, title = Identifying and managing problematic trials: A research integrity assessment tool for randomized controlled trials in evidence synthesis, pages = 357–369, volume = 14, number = 3, journal = Research synthesis methods, doi = 10.1002/jrsm.1599,
md5:a31968577e5ff9bfb719faf1e00a831e
2023-06-06T12:36:48+00:00
/tmp/phpqnoJwR
bibtex
647f286071dce5.55788422
Research Synthesis Methods 2023, 14(3):357-369. DOI: 10.1002/jrsm.1599
false
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Stephanie Weibel
Maria Popp
Stefanie Reis
Nicole Skoetz
Paul Garner
Emma Sydenham
eng
uncontrolled
COVID-19 pandemic
eng
uncontrolled
systematic review
eng
uncontrolled
research integrity
eng
uncontrolled
randomized controlled trial
eng
uncontrolled
good clinical practice
eng
uncontrolled
evidence synthesis
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/31823/Weibel_Research.pdf
6480
2012
eng
article
1
2013-03-16
--
--
Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy
Background: Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic. Methods: Here, we describe a novel approach to optimize combination therapy of oncolytic virus and chemotherapy utilizing virus-encoding hyper-IL-6, GLV-1h90, to reduce chemotherapy-associated side effects. Results: We showed that the hyper-IL-6 cytokine was successfully produced by GLV-1h90 and was functional both in cell culture as well as in tumor-bearing animals, in which the cytokine-producing vaccinia virus strain was well tolerated. When combined with the chemotherapeutic mitomycin C, the anti-tumor effect of the oncolytic virotherapy was significantly enhanced. Moreover, hyper-IL-6 expression greatly reduced the time interval during which the mice suffered from chemotherapy-induced thrombocytopenia. Conclusion: Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects.
urn:nbn:de:bvb:20-opus-75224
7522
In: Journal of Translational Medicine (2012) 10: 9, doi:10.1186/1479-5876-10-9
Julia B. Sturm
Michael Hess
Stephanie Weibel
Nanhei G. Chen
Yong A. Yu
Quian Zhang
Ulrike Donat
Cora Reiss
Stepan Gambaryan
Georg Krohne
Jochen Stritzker
Aladar A. Szalay
deu
swd
Biologie
eng
uncontrolled
vaccinia virus
eng
uncontrolled
cancer
eng
uncontrolled
cytokine
eng
uncontrolled
hyper-IL-6
eng
uncontrolled
oncolysis
eng
uncontrolled
chemotherapy
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2012
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6480/017_1479_5876_10_9.pdf
11938
2014
eng
e104337
8
9
article
1
2015-09-29
--
--
Evaluation of a New Recombinant Oncolytic Vaccinia Virus Strain GLV-5b451 for Feline Mammary Carcinoma Therapy
Virotherapy on the basis of oncolytic vaccinia virus (VACV) infection is a promising approach for cancer therapy. In this study we describe the establishment of a new preclinical model of feline mammary carcinoma (FMC) using a recently established cancer cell line, DT09/06. In addition, we evaluated a recombinant vaccinia virus strain, GLV-5b451, expressing the anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as an oncolytic agent against FMC. Cell culture data demonstrate that GLV-5b451 virus efficiently infected, replicated in and destroyed DT09/06 cancer cells. In the selected xenografts of FMC, a single systemic administration of GLV-5b451 led to significant inhibition of tumor growth in comparison to untreated tumor-bearing mice. Furthermore, tumor-specific virus infection led to overproduction of functional scAb GLAF-2, which caused drastic reduction of intratumoral VEGF levels and inhibition of angiogenesis.
In summary, here we have shown, for the first time, that the vaccinia virus strains and especially GLV-5b451 have great potential for effective treatment of FMC in animal model.
PLoS ONE
10.1371/journal.pone.0104337
urn:nbn:de:bvb:20-opus-119387
PLoS ONE 9(8): e104337. doi:10.1371/journal.pone.0104337
Marion Adelfinger
Ivaylo Gentschev
Julio Grimm de Guibert
Stephanie Weibel
Johanna Langbein-Laugwitz
Barbara Härtl
Hugo Murua Escobar
Ingo Nolte
Nanhai G. Chen
Richard J. Aguilar
Yong A. Yu
Qian Zhang
Alexa Frentzen
Aladar A. Szalay
eng
uncontrolled
antibodies
eng
uncontrolled
cancer treatment
eng
uncontrolled
carcinomas
eng
uncontrolled
vaccinia virus
eng
uncontrolled
oncolytic viruses
eng
uncontrolled
viral replication
eng
uncontrolled
cell cultures
eng
uncontrolled
enzyme-linked immunoassays
Krankheiten
open_access
Institut für Molekulare Infektionsbiologie
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11938/033_Adelfinger_PLOS_ONE.pdf
13531
2011
eng
e22069
7
6
article
1
2016-06-22
--
--
Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68
Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC) in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 efficiently colonized, replicated in, and did lyse these cancer cells in culture. Experiments with HuH7 and PLC xenografts have revealed that a single intravenous injection (i.v.) of mice with GLV-1h68 resulted in a significant reduction of primary tumor sizes compared to uninjected controls. In addition, replication of GLV-1h68 in tumor cells led to strong inflammatory and oncolytic effects resulting in intense infiltration of MHC class II-positive cells like neutrophils, macrophages, B cells and dendritic cells and in up-regulation of 13 pro-inflammatory cytokines. Furthermore, GLV-1h68 infection of PLC tumors inhibited the formation of hemorrhagic structures which occur naturally in PLC tumors. Interestingly, we found a strongly reduced vascular density in infected PLC tumors only, but not in the non-hemorrhagic HuH7 tumor model. These data demonstrate that the GLV-1h68 vaccinia virus may have an enormous potential for treatment of human hepatocellular carcinoma in man.
PLOS ONE
10.1371/journal.pone.0022069
urn:nbn:de:bvb:20-opus-135319
PLoS ONE 6(7): e22069. doi:10.1371/journal.pone.0022069
false
true
Ivaylo Gentschev
Meike Müller
Marion Adelfinger
Stephanie Weibel
Friedrich Grummt
Martina Zimmermann
Michael Bitzer
Martin Heisig
Qian Zhang
Yong A. Yu
Nanhai G. Chen
Jochen Stritzker
Ulrich M. Lauer
Aladar A. Szalay
eng
uncontrolled
Breast-tumors
eng
uncontrolled
Nude-mice
eng
uncontrolled
In-vivo
eng
uncontrolled
Cancer
eng
uncontrolled
Inhibitor
eng
uncontrolled
Tissue
eng
uncontrolled
Agent
eng
uncontrolled
COX-2
Medizin und Gesundheit
open_access
Institut für Molekulare Infektionsbiologie
Rudolf-Virchow-Zentrum
Lehrstuhl für Biochemie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13531/044_Gentschev_PLoSONE.pdf
25947
2021
eng
188–197
3
14
article
1
--
--
--
Drugs for preventing postoperative nausea and vomiting in adults after general anesthesia: An abridged Cochrane network meta-analysis
Objective
In this abridged version of the recently published Cochrane review on antiemetic drugs, we summarize its most important findings and discuss the challenges and the time needed to prepare what is now the largest Cochrane review with network meta-analysis in terms of the number of included studies and pages in its full printed form.
Methods
We conducted a systematic review with network meta-analyses to compare and rank single antiemetic drugs and their combinations belonging to 5HT₃-, D₂-, NK₁-receptor antagonists, corticosteroids, antihistamines, and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anesthesia.
Results
585 studies (97 516 participants) testing 44 single drugs and 51 drug combinations were included. The studies’ overall risk of bias was assessed as low in only 27% of the studies. In 282 studies, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared to placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single NK1 receptor antagonists were as effective as other drug combinations. Of the 10 effective single drugs, certainty of evidence was high for aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron, while moderate for fosaprepitant and droperidol. For serious adverse events (SAEs), any adverse event (AE), and drug-class specific side effects evidence for intervention effects was mostly not convincing.
Conclusions
There is high or moderate evidence for at least seven single drugs preventing postoperative vomiting. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.
Journal of Evidence-Based Medicine
10.1111/jebm.12429
urn:nbn:de:bvb:20-opus-259470
publish
Journal of Evidence-Based Medicine 2021, 14(3):188–197. DOI: 10.1111/jebm.12429
false
true
CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International
Stephanie Weibel
Nathan L. Pace
Maximilian S. Schaefer
Diana Raj
Tobias Schlesinger
Patrick Meybohm
Peter Kienbaum
Leopold H. J. Eberhart
Peter Kranke
eng
uncontrolled
systematic review,
eng
uncontrolled
antiemetics
eng
uncontrolled
network meta-analysis
eng
uncontrolled
postoperative nausea and vomiting
eng
uncontrolled
vomiting
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/25947/Weibel_Evidence.pdf
11016
2014
eng
article
1
2015-02-25
--
--
Combination treatment with oncolytic Vaccinia virus and cyclophosphamide results in synergistic antitumor effects in human lung adenocarcinoma bearing mice
Background
The capacity of the recombinant Vaccinia virus GLV-1h68 as a single agent to efficiently treat different human or canine cancers has been shown in several preclinical studies. Currently, its human safety and efficacy are investigated in phase I/II clinical trials. In this study we set out to evaluate the oncolytic activity of GLV-1h68 in the human lung adenocarcinoma cell line PC14PE6-RFP in cell cultures and analyzed the antitumor potency of a combined treatment strategy consisting of GLV-1h68 and cyclophosphamide (CPA) in a mouse model of PC14PE6-RFP lung adenocarcinoma.
Methods
PC14PE6-RFP cells were treated in cell culture with GLV-1h68. Viral replication and cell survival were determined by plaque assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. Subcutaneously implanted PC14PE6-RFP xenografts were treated by systemic injection of GLV-1h68, CPA or a combination of both. Tumor growth and viral biodistribution were monitored and immune-related antigen profiling of tumor lysates was performed.
Results
GLV-1h68 efficiently infected, replicated in and lysed human PC14PE6-RFP cells in cell cultures. PC14PE6-RFP tumors were efficiently colonized by GLV-1h68 leading to much delayed tumor growth in PC14PE6-RFP tumor-bearing nude mice. Combination treatment with GLV-1h68 and CPA significantly improved the antitumor efficacy of GLV-1h68 and led to an increased viral distribution within the tumors. Pro-inflammatory cytokines and chemokines were distinctly elevated in tumors of GLV-1h68-treated mice. Factors expressed by endothelial cells or present in the blood were decreased after combination treatment. A complete loss in the hemorrhagic phenotype of the PC14PE6-RFP tumors and a decrease in the number of blood vessels after combination treatment could be observed.
Conclusions
CPA and GLV-1h68 have synergistic antitumor effects on PC14PE6-RFP xenografts. We strongly suppose that in the PC14PE6-RFP model the enhanced tumor growth inhibition achieved by combining GLV-1h68 with CPA is due to an effect on the vasculature rather than an immunosuppressive action of CPA. These results provide evidence to support further preclinical studies of combining GLV-1h68 and CPA in other highly angiogenic tumor models. Moreover, data presented here demonstrate that CPA can be combined successfully with GLV-1h68 based oncolytic virus therapy and therefore might be promising as combination therapy in human clinical trials.
10.1186/1479-5876-12-197
urn:nbn:de:bvb:20-opus-110168
Journal of Translational Medicine 2014, 12:197
Elisabeth Hofmann
Stephanie Weibel
Aladar A. Szalay
eng
uncontrolled
Vaccinia virus
eng
uncontrolled
Chemotherapy
eng
uncontrolled
Combination therapy
eng
uncontrolled
Cyclophosphamide
eng
uncontrolled
Lung cancer
Biochemie
open_access
Institut für Molekulare Infektionsbiologie
Rudolf-Virchow-Zentrum
Lehrstuhl für Biochemie
Förderzeitraum 2014
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11016/034_Hofmann_TranslationalMedicine.pdf
11967
2014
eng
e98533
6
9
article
1
2015-10-02
--
--
Characterization of Metastasis Formation and Virotherapy in the Human C33A Cervical Cancer Model
More than 90% of cancer mortalities are due to cancer that has metastasized. Therefore, it is crucial to intensify research on metastasis formation and therapy. Here, we describe for the first time the metastasizing ability of the human cervical cancer cell line C33A in athymic nude mice after subcutaneous implantation of tumor cells. In this model, we demonstrated a steady progression of lumbar and renal lymph node metastases during tumor development. Besides predominantly occurring lymphatic metastases, we visualized the formation of hematogenous metastases utilizing red fluorescent protein (RFP) expressing C33A-RFP cells. RFP positive cancer cells were found migrating in blood vessels and forming micrometastases in lungs of tumor-bearing mice. Next, we set out to analyze the influence of oncolytic virotherapy in the C33A-RFP model and demonstrated an efficient virus-mediated reduction of tumor size and metastatic burden. These results suggest the C33A-RFP cervical cancer model as a new platform to analyze cancer metastases as well as to test novel treatment options to combat metastases.
PLoS ONE
10.1371/journal.pone.0098533
1932-6203
24887184
urn:nbn:de:bvb:20-opus-119674
PLoS ONE 9(6): e98533. doi:10.1371/journal.pone.0098533
Ulrike Donat
Juliane Rother
Simon Schäfer
Michael Hess
Barbara Härtl
Christina Kober
Johanna Langbein-Laugwitz
Jochen Stritzker
Nanhai G. Chen
Richard J. Aguilar
Stephanie Weibel
Alandar A. Szalay
eng
uncontrolled
metastasis
eng
uncontrolled
renal cancer
eng
uncontrolled
oncolytic viruses
eng
uncontrolled
lymph nodes
eng
uncontrolled
kidneys
eng
uncontrolled
lung and intrathoracic tumors
eng
uncontrolled
secondary lung tumors
eng
uncontrolled
cancer treatment
Krankheiten
open_access
Rudolf-Virchow-Zentrum
Lehrstuhl für Biochemie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11967/047_Donat_PLOS_ONE.pdf
25522
2022
eng
2
11
article
1
--
2022-01-13
--
Awake prone positioning, high-flow nasal oxygen and non-invasive ventilation as non-invasive respiratory strategies in COVID-19 acute respiratory failure: a systematic review and meta-analysis
Background: Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. Methods: We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. Results: Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65–1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03–1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71–0.96) but may have little or no effect on mortality (RR: 1.08, 0.51–2.31). Conclusions: Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.
Journal of Clinical Medicine
2077-0383
10.3390/jcm11020391
urn:nbn:de:bvb:20-opus-255225
2022-02-09T01:19:42+00:00
sword
swordwue
attachment; filename=deposit.zip
b2c23d19db4b41f6706f5abcef957ca7
Journal of Clinical Medicine (2022) 11:2, 391. https://doi.org/10.3390/jcm11020391
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Benedikt Schmid
Mirko Griesel
Anna-Lena Fischer
Carolina S. Romero
Maria-Inti Metzendorf
Stephanie Weibel
Falk Fichtner
eng
uncontrolled
respiratory failure
eng
uncontrolled
non-invasive ventilation
eng
uncontrolled
high-flow nasal cannula
eng
uncontrolled
awake prone positioning
eng
uncontrolled
COVID-19
eng
uncontrolled
systematic review
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/25522/jcm-11-00391-v2.pdf