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  • 1
    In: Endocrine-Related Cancer, Bioscientifica, Vol. 25, No. 4 ( 2018-04), p. 437-451
    Abstract: Adrenocortical cancer (ACC) is an orphan malignancy that results in heterogeneous clinical phenotypes and molecular genotypes. There are no curative treatments for this deadly cancer with 35% survival at five years. Our understanding of the underlying pathobiology and our ability to test novel therapeutic targets has been limited due to the lack of preclinical models. Here, we report the establishment of two new ACC cell lines and corresponding patient-derived xenograft (PDX) models. CU-ACC1 cell line and PDX were derived from a perinephric metastasis in a patient whose primary tumor secreted aldosterone. CU-ACC2 cell line and PDX were derived from a liver metastasis in a patient with Lynch syndrome. Short tandem repeat profiling confirmed consistent matches between human samples and models. Both exomic and RNA sequencing profiling were performed on the patient samples and the models, and hormonal secretion was evaluated in the new cell lines. RNA sequencing and immunohistochemistry confirmed the expression of adrenal cortex markers in the PDXs and human tumors. The new cell lines replicate two of the known genetic models of ACC. CU-ACC1 cells had a mutation in CTNNB1 and secreted cortisol but not aldosterone. CU-ACC2 cells had a TP53 mutation and loss of MSH2 consistent with the patient’s known germline mutation causing Lynch syndrome. Both cell lines can be transfected and transduced with similar growth rates. These new preclinical models of ACC significantly advance the field by allowing investigation of underlying molecular mechanisms of ACC and the ability to test patient-specific therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 1351-0088 , 1479-6821
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2018
    detail.hit.zdb_id: 2010895-3
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  • 2
    Online Resource
    Online Resource
    Cambridge University Press (CUP) ; 2002
    In:  German Law Journal Vol. 3, No. 10 ( 2002-10)
    In: German Law Journal, Cambridge University Press (CUP), Vol. 3, No. 10 ( 2002-10)
    Abstract: Child protection practice has undergone major changes in the last decades. While traditionally welfare institutions as well as the law itself were mainly concerned with orphans and children of unmarried mothers, nowadays the practice focuses on children in need of protection because they have been neglected or abused by their parents. And yet, child protection measures have not been the focus of research, discussion and reform like other areas of the law concerned with children, for example parental custody after divorce. Recent reforms – or plans for reform – in some continental European states are not to be expected to bring substantive changes.
    Type of Medium: Online Resource
    ISSN: 2071-8322
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2002
    detail.hit.zdb_id: 2074128-5
    SSG: 2
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  • 3
    In: Clinical Oral Implants Research, Wiley, Vol. 32, No. 4 ( 2021-04), p. 470-486
    Abstract: To assess clinical and patient‐reported outcomes of implant‐prosthetic rehabilitations in patients with a history of head–neck cancer (HNC), treated with tumor resection without (TR) or with adjuvant radiotherapy (TR/RT). A healthy cohort rehabilitated with the same reconstructive protocols served as control group (C). Materials and Methods A total of 28 women and 29 men were considered in the present retrospective study. Participants received 322 implants, finally supporting 79 prosthetic reconstructions. Primary outcome was the assessment of implant and prosthetic survival rates. Furthermore peri‐implant soft tissue parameters (attached peri‐implant mucosa, AM; modified bleeding and plaque indices, mBI/mPI; probing depth, PD) and prosthetic technical complications were documented. Patient‐reported outcome measures (PROMs) by means of visual analog scales (VAS) and the Oral Health Impact Profile German 14 form (OHIP G14) were collected. For statistical purposes Chi‐square and Mann–Whitney‐ U ‐Test were adapted. Results After a mean follow‐up of 81.2 ± 50.3 months, implant survival rate was 98.1% (HNC‐TR), 98.2% (HNC‐TR/RT) and 100.0% (C), respectively (four implants failed in the HNC groups). HNC‐TR/RT showed significant higher mPI and mBI compared to C. Within HNC‐TR/RT, vestibuloplasty significantly reduced mBI and PD values. No failures occurred at the prosthetic level. Overall, higher VAS scores were reported for bar‐ compared with Locator‐retained prostheses. Furthermore, increased OHIP G14 values resulted for HNC‐TR/RT. Conclusions High survival rates on implant and prosthetic level were observed. The use of soft tissue grafts resulted in stabilization of the peri‐implant mucosa in irradiated patients. In terms of retention and chewing ability, participants preferred bars over Locator attachments.
    Type of Medium: Online Resource
    ISSN: 0905-7161 , 1600-0501
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2027104-9
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