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Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer.
Lõhmussaar, Kadi; Oka, Rurika; Espejo Valle-Inclan, Jose; Smits, Milou H H; Wardak, Hila; Korving, Jeroen; Begthel, Harry; Proost, Natalie; van de Ven, Marieke; Kranenburg, Onno W; Jonges, Trudy G N; Zweemer, Ronald P; Veersema, Sebastiaan; van Boxtel, Ruben; Clevers, Hans.
Afiliación
  • Lõhmussaar K; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, the Netherlands.
  • Oka R; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, the Netherlands; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands.
  • Espejo Valle-Inclan J; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, the Netherlands; Center for Molecular Medicine, UMC Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
  • Smits MHH; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
  • Wardak H; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
  • Korving J; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, the Netherlands.
  • Begthel H; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, the Netherlands.
  • Proost N; Preclinical Intervention Unit of the Mouse Clinic for Cancer and Ageing (MCCA) at the NKI, Plesmanlaan 121, 1066 CX, the Netherlands.
  • van de Ven M; Preclinical Intervention Unit of the Mouse Clinic for Cancer and Ageing (MCCA) at the NKI, Plesmanlaan 121, 1066 CX, the Netherlands.
  • Kranenburg OW; Utrecht Platform for Organoid Technology (U-PORT), UMC Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
  • Jonges TGN; Department of Pathology, UMC Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
  • Zweemer RP; Department of Gynaecological Oncology, Cancer Center, UMC Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
  • Veersema S; Department of Reproductive Medicine and Gynaecology, Division Woman and Baby, UMC Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
  • van Boxtel R; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, the Netherlands; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands.
  • Clevers H; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, the Netherlands; Princess Máxima Center for Pediatric Oncology, Heidelberglaan
Cell Stem Cell ; 28(8): 1380-1396.e6, 2021 08 05.
Article en En | MEDLINE | ID: mdl-33852917
Cervical cancer is a common gynecological malignancy often caused by high-risk human papillomavirus. There is a paucity of human-derived culture systems to study the cervical epithelium and the cancers derived thereof. Here we describe a long-term culturing protocol for ecto- and endocervical epithelia that generates 3D organoids that stably recapitulate the two tissues of origin. As evidenced for HSV-1, organoid-based cervical models may serve to study sexually transmitted infections. Starting from Pap brush material, a small biobank of tumoroids derived from affected individuals was established that retained the causative human papillomavirus (HPV) genomes. One of these uniquely carried the poorly characterized HPV30 subtype, implying a potential role in carcinogenesis. The tumoroids displayed differential responses to common chemotherapeutic agents and grew as xenografts in mice. This study describes an experimental platform for cervical (cancer) research and for future personalized medicine approaches.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Cuello Uterino Límite: Animals / Female / Humans Idioma: En Revista: Cell Stem Cell Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Cuello Uterino Límite: Animals / Female / Humans Idioma: En Revista: Cell Stem Cell Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos