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Novel zebrafish pat...
Novel zebrafish patient-derived tumor xenograft methodology for evaluating efficacy of immune-stimulating bcg therapy in urinary bladder cancer
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- Kowald, Saskia (författare)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten
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- Huge, Ylva (författare)
- Karolinska Institutet,Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Urologiska kliniken i Östergötland
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- Tandiono, Decky (författare)
- BioReper AB, SE-58213 Linkoping, Sweden
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- Ali, Zaheer (författare)
- BioReper AB, SE-58213 Linkoping, Sweden
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- Vazquez-Rodriguez, Gabriela (författare)
- BioReper AB, SE-58213 Linkoping, Sweden
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- Erkstam, Anna (författare)
- BioReper AB, SE-58213 Linkoping, Sweden
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- Fahlgren, Anna (författare)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,BioReper AB, SE-58213 Linkoping, Sweden
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- Sherif, Amir (författare)
- Linköpings universitet,Umeå universitet,Urologi och andrologi,Department of Biomedical and Clinical Sciences, Division of Urology, Linköping University, Linköping, Sweden,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Umea Univ, Sweden
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- Cao, Yihai (författare)
- Karolinska Inst, Sweden
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- Jensen, Lasse (författare)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Klinisk farmakologi,BioReper AB, SE-58213 Linkoping, Sweden
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(creator_code:org_t)
- 2023-02-03
- 2023
- Engelska.
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:3
- Relaterad länk:
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https://doi.org/10.3...
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https://umu.diva-por... (primary) (Raw object)
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- BACKGROUND: Bacillus Calmette-Guérin (BCG) immunotherapy is the standard-of-care adjuvant therapy for non-muscle-invasive bladder cancer in patients at considerable risk of disease recurrence. Although its exact mechanism of action is unknown, BCG significantly reduces this risk in responding patients but is mainly associated with toxic side-effects in those facing treatment resistance. Methods that allow the identification of BCG responders are, therefore, urgently needed.METHODS: Fluorescently labelled UM-UC-3 cells and dissociated patient tumor samples were used to establish zebrafish tumor xenograft (ZTX) models. Changes in the relative primary tumor size and cell dissemination to the tail were evaluated via fluorescence microscopy at three days post-implantation. The data were compared to the treatment outcomes of the corresponding patients. Toxicity was evaluated based on gross morphological evaluation of the treated zebrafish larvae.RESULTS: BCG-induced toxicity was avoided by removing the water-soluble fraction of the BCG formulation prior to use. BCG treatment via co-injection with the tumor cells resulted in significant and dose-dependent primary tumor size regression. Heat-inactivation of BCG decreased this effect, while intravenous BCG injections were ineffective. ZTX models were successfully established for six of six patients based on TUR-B biopsies. In two of these models, significant tumor regression was observed, which, in both cases, corresponded to the treatment response in the patients.CONCLUSIONS: The observed BCG-related anti-tumor effect indicates that ZTX models might predict the BCG response and thereby improve treatment planning. More experiments and clinical studies are needed, however, to elucidate the BCG mechanism and estimate the predictive value.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Annan klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Other Clinical Medicine (hsv//eng)
Nyckelord
- BCG
- PDX
- cancer
- immune-oncology
- personalized medicine
- xenograft
- zebrafish
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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