Author
Kristina A. Butler
Other affiliations: University of Insubria
Bio: Kristina A. Butler is an academic researcher from Mayo Clinic. The author has contributed to research in topics: Ovarian cancer & Hysterectomy. The author has an hindex of 10, co-authored 34 publications receiving 356 citations. Previous affiliations of Kristina A. Butler include University of Insubria.
Topics: Ovarian cancer, Hysterectomy, Medicine, Endometrial cancer, Carboplatin
Papers
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TL;DR: This is the largest known living tumor bank of patient-derived, ovarian tumorgraft models that can be applied to the development of personalized cancer treatment and response to platinum chemotherapy correlates with the source patient.
Abstract: Purpose: Ovarian cancer has a high recurrence and mortality rate. A barrier to improved outcomes includes a lack of accurate models for preclinical testing of novel therapeutics. Experimental Design: Clinically relevant, patient-derived tumorgraft models were generated from sequential patients and the first 168 engrafted models are described. Fresh ovarian, primary peritoneal, and fallopian tube carcinomas were collected at the time of debulking surgery and injected intraperitoneally into severe combined immunodeficient mice. Results: Tumorgrafts demonstrated a 74% engraftment rate with microscopic fidelity of primary tumor characteristics. Low-passage tumorgrafts also showed comparable genomic aberrations with the corresponding primary tumor and exhibit gene set enrichment of multiple ovarian cancer molecular subtypes, similar to patient tumors. Importantly, each of these tumorgraft models is annotated with clinical data and for those that have been tested, response to platinum chemotherapy correlates with the source patient. Conclusions: Presented herein is the largest known living tumor bank of patient-derived, ovarian tumorgraft models that can be applied to the development of personalized cancer treatment. Clin Cancer Res; 20(5); 1288–97. ©2014 AACR .
167 citations
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TL;DR: Ovarian cancer PDXs which developed human lymphomas are characterized and investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth.
42 citations
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TL;DR: The widespread adoption of minimally invasive surgery is associated with substantial decreases in 30-day morbidity, readmission, and reoperation for women treated for endometrial cancer in the United States.
37 citations
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27 citations
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01 Oct 2020TL;DR: Ribociclib and letrozole have promising clinical activity in relapsed ER-positive OC and EC, particularly in LGSOC and relapsedER-positive grade 1 and 2 EC.
Abstract: Objective We describe a phase II clinical trial of the combination of ribociclib and letrozole for treatment of relapsed oestrogen receptor (ER)-positive ovarian cancer (OC) and endometrial cancer (EC). The primary endpoint was the proportion of patients alive, progression-free survival (PFS), and still on treatment at 12 weeks (PFS12), with 45% or greater considered positive. Methods Patients with measurable, relapsed ER-positive OC or EC (platinum-sensitive or resistant) were eligible and treated with 400 mg of oral ribociclib and 2.5 mg of oral letrozole daily. Patient-derived xenografts (PDXs) were created from imaging-guided tumour biopsies. Results Forty patients (20 OC and 20 EC) were enrolled. A PFS12 of 55% was observed in the EC cohort and 50% in the OC cohort. A PFS greater or equal to 24 weeks (PFS24) was seen in 20% (4/20) of the OC cohort and 35% (7/20) of the EC cohort. The greatest benefit was seen in low-grade serous OC (LGSOC) (3/3, 100% PFS24) and grades 1 and 2 EC (5/11, 45% PFS24). All three LGSOC patients obtained at least a partial response lasting for over 2 years, with two of the three patients still on treatment. PDX tumour engraftment was feasible in 45% of patients. Positive survival effects of the combination of ribociclib and letrozole were observed in two of three EC PDX models. Conclusion Ribociclib and letrozole have promising clinical activity in relapsed ER-positive OC and EC, particularly in LGSOC and relapsed ER-positive grade 1 and 2 EC. Generation of PDX models is feasible with positive survival effects observed in EC models. Trial registration number ClinicalTrials.gov registry ( NCT02657928 ).
27 citations
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TL;DR: The four most commonly used spherical cancer models in cancer research are proposed based on culture methods for obtaining them and on subsequent differences in sphere biology: the multicellular tumor spheroid model, first described in the early 70s and obtained by culture of cancer cell lines under nonadherent conditions; tumorospheres, a model of cancer stem cell expansion established in a serum-free medium supplemented with growth factors.
861 citations
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Garvan Institute of Medical Research1, Peter MacCallum Cancer Centre2, Queen Mary University of London3, John Radcliffe Hospital4, Cedars-Sinai Medical Center5, University of Oxford6, Stanford University7, Harvard University8, Imperial College London9, University of Cambridge10, Johns Hopkins University11, University Hospital of Lausanne12, University of Pennsylvania13, University of Manchester14, French Institute of Health and Medical Research15, University of Edinburgh16, Walter and Eliza Hall Institute of Medical Research17, University of British Columbia18, University of Chicago19, Memorial Sloan Kettering Cancer Center20, University of Glasgow21, University College London22, University of Toronto23, Indiana University24, Translational Genomics Research Institute25
TL;DR: This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015 and aims to reduce incidence and improve outcomes for women with this disease.
Abstract: High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015.
801 citations
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Innsbruck Medical University1, The Catholic University of America2, First Faculty of Medicine, Charles University in Prague3, Copenhagen University Hospital4, University of Cologne5, University College London6, Leiden University Medical Center7, Institut Gustave Roussy8, Agostino Gemelli University Polyclinic9, Imperial College London10, University of Navarra11, Johannes Kepler University of Linz12, Erasmus University Rotterdam13, Humboldt University of Berlin14, Medical University of Vienna15, The Royal Marsden NHS Foundation Trust16, University of Amsterdam17, Dresden University of Technology18, European Institute of Oncology19
TL;DR: A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions as mentioned in this paper, and the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncologies (ESTRO), and the EPSP jointly decided to update these evidence-base guidelines and to cover new topics in order to improve the quality of care for women with endometrium carcinoma across Europe and worldwide.
Abstract: A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.
584 citations
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TL;DR: In this review, the current challenges and limitations of animal models are discussed, with a focus on the fit-for-purpose validation and the use of humanized mouse models and preclinical applications of clinical features.
352 citations
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25 Oct 2018
TL;DR: Passive immunotherapies targeting clonal plasma cells and directly accelerating removal of amyloid deposits promise to further improve the overall outlook of this increasingly treatable disease.
Abstract: Systemic immunoglobulin light chain amyloidosis is a protein misfolding disease caused by the conversion of immunoglobulin light chains from their soluble functional states into highly organized amyloid fibrillar aggregates that lead to organ dysfunction. The disease is progressive and, accordingly, early diagnosis is vital to prevent irreversible organ damage, of which cardiac damage and renal damage predominate. The development of novel sensitive biomarkers and imaging technologies for the detection and quantification of organ involvement and damage is facilitating earlier diagnosis and improved evaluation of the efficacy of new and existing therapies. Treatment is guided by risk assessment, which is based on levels of cardiac biomarkers; close monitoring of clonal and organ responses guides duration of therapy and changes in regimen. Several new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, along with high-dose chemotherapy and autologous haematopoietic stem cell transplantation, have led to rapid and deep suppression of amyloid light chain production in the majority of patients. However, effective therapies for patients with advanced cardiac involvement are an unmet need. Passive immunotherapies targeting clonal plasma cells and directly accelerating removal of amyloid deposits promise to further improve the overall outlook of this increasingly treatable disease.
321 citations