Advantages and limitations of 3D organoids and ex vivo tumor tissue culture in personalized medicine for prostate cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00098892%3A_____%2F22%3A10157765" target="_blank" >RIV/00098892:_____/22:10157765 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/22:73614939

Výsledek na webu

<a href="https://www.linkos.cz/english-summary/klinicka-onkologie-journal/2022-12-15-6-en/vyhody-a-omezeni-3d-organoidu-a-ex-vivo-kultivace-nadorovych-tkani-v-personalizo-1/" target="_blank" >https://www.linkos.cz/english-summary/klinicka-onkologie-journal/2022-12-15-6-en/vyhody-a-omezeni-3d-organoidu-a-ex-vivo-kultivace-nadorovych-tkani-v-personalizo-1/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.48095/ccko2022473" target="_blank" >10.48095/ccko2022473</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Advantages and limitations of 3D organoids and ex vivo tumor tissue culture in personalized medicine for prostate cancer

Popis výsledku v původním jazyce

Background: Current in vitro model systems do not fully reflect the biological and clinical diversity of prostate cancer (PCa). Organoids are 3D in vitro cell cultures that may better recapitulate disease heterogeneity and retain parental tumor characteristics. Short-term ex vivo culture of PCa tissues may also facilitate drug testing in personalized medicine. Materials and methods: For organoid culture, we have processed both cancer and normal tissues from 50 patients who underwent radical prostatectomy or transurethral resection of the prostate. In addition, we exploited the ex vivo tissue culture technique and performed short-term chemotherapy assay using gemcitabine and Chk1 inhibitor MU380 in 10 patient samples. Results: In total, we were able to cultivate organoids from 58% of tumors (29/50) and 69% of normal tissue (20/29). Immunohistochemical staining of two representative cases revealed cell positivity for pan-cytokeratin confirming the presence of epithelial cells. However, the overexpression of AMACR and ERG proteins in tumors was not recapitulated in organoids. Another limitation was the propagation of organoids only up to 3 weeks till the first passage. Next, a short-term drug test was performed for ten patients using ex vivo tissue culture. Samples from prostatectomies mostly presented a low proliferation rate as assessed by Ki-67 staining. Another drawback of this approach was inconsistent tissue morphology among particular tissue fragments. Only one case showed a high proliferation rate for drug testing and tumor tissue was present in all tested samples. In our work, we also provide an overview of recent studies and a detailed comparison of culture conditions. Conclusion: We have established cultures of both organoids and tissue fragments from PCa patient samples. However, the expression of tumor markers was not recapitulated in organoids. Inconsistent morphology among tissue fragments and low proliferation hampered the interpretation of the drug testing in most cases. Still, these approaches may be promising using tissues from metastatic castration-resistant prostate cancer.

Název v anglickém jazyce

Advantages and limitations of 3D organoids and ex vivo tumor tissue culture in personalized medicine for prostate cancer

Popis výsledku anglicky

Background: Current in vitro model systems do not fully reflect the biological and clinical diversity of prostate cancer (PCa). Organoids are 3D in vitro cell cultures that may better recapitulate disease heterogeneity and retain parental tumor characteristics. Short-term ex vivo culture of PCa tissues may also facilitate drug testing in personalized medicine. Materials and methods: For organoid culture, we have processed both cancer and normal tissues from 50 patients who underwent radical prostatectomy or transurethral resection of the prostate. In addition, we exploited the ex vivo tissue culture technique and performed short-term chemotherapy assay using gemcitabine and Chk1 inhibitor MU380 in 10 patient samples. Results: In total, we were able to cultivate organoids from 58% of tumors (29/50) and 69% of normal tissue (20/29). Immunohistochemical staining of two representative cases revealed cell positivity for pan-cytokeratin confirming the presence of epithelial cells. However, the overexpression of AMACR and ERG proteins in tumors was not recapitulated in organoids. Another limitation was the propagation of organoids only up to 3 weeks till the first passage. Next, a short-term drug test was performed for ten patients using ex vivo tissue culture. Samples from prostatectomies mostly presented a low proliferation rate as assessed by Ki-67 staining. Another drawback of this approach was inconsistent tissue morphology among particular tissue fragments. Only one case showed a high proliferation rate for drug testing and tumor tissue was present in all tested samples. In our work, we also provide an overview of recent studies and a detailed comparison of culture conditions. Conclusion: We have established cultures of both organoids and tissue fragments from PCa patient samples. However, the expression of tumor markers was not recapitulated in organoids. Inconsistent morphology among tissue fragments and low proliferation hampered the interpretation of the drug testing in most cases. Still, these approaches may be promising using tissues from metastatic castration-resistant prostate cancer.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Klinická onkologie

ISSN

0862-495X

e-ISSN

1802-5307

Svazek periodika

35

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

9

Strana od-do

473-481

Kód UT WoS článku

—

EID výsledku v databázi Scopus

2-s2.0-85143963304