A5088406750- Ovarian cancer diagnosis and treatment
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- Cancer Cells and Metastasis
- Endometrial and Cervical Cancer Treatments
- Estrogen and related hormone effects
- Epigenetics and DNA Methylation
- Proteoglycans and glycosaminoglycans research
- Radiopharmaceutical Chemistry and Applications
- Advanced Breast Cancer Therapies
- CRISPR and Genetic Engineering
- Uterine Myomas and Treatments
- Nanoparticle-Based Drug Delivery
- Cancer-related Molecular Pathways
- Growth Hormone and Insulin-like Growth Factors
- Metastasis and carcinoma case studies
- FOXO transcription factor regulation
- Endometriosis Research and Treatment
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Sarcoma Diagnosis and Treatment
- Metabolism, Diabetes, and Cancer
- Angiogenesis and VEGF in Cancer
- Immune Cell Function and Interaction
Mayo Clinic in Arizona
2016-2025
Mayo Clinic
2015-2025
Gynecologic Oncology Group
2014-2025
WinnMed
2008-2025
Mayo Clinic in Florida
2015-2021
Translational Research Institute
2020
Mater Research
2020
The University of Queensland
2020
Cedars-Sinai Medical Center
2014
Department of Medical Sciences
2014
Abstract Purpose: Ovarian cancer has a high recurrence and mortality rate. A barrier to improved outcomes includes lack of accurate models for preclinical testing novel therapeutics. Experimental Design: Clinically relevant, patient-derived tumorgraft were generated from sequential patients the first 168 engrafted are described. Fresh ovarian, primary peritoneal, fallopian tube carcinomas collected at time debulking surgery injected intraperitoneally into severe combined immunodeficient...
Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study evolution, mechanisms of drug response and resistance, tailoring chemotherapeutic approaches for individual patients. The lack robust standards reporting on PDX has hampered the ability researchers find relevant associated data. Here we present minimal information standard (PDX-MI) generation, quality assurance, use models. PDX-MI defines describing clinical attributes a...
Attenuated measles virus (MV) strains are promising agents currently being tested against solid tumors or hematologic malignancies in ongoing phase I and II clinical trials; factors determining oncolytic virotherapy success remain poorly understood, however. We performed RNA sequencing gene set enrichment analysis to identify pathways differentially activated MV-resistant (n = 3) -permissive 2) derived from resected human glioblastoma (GBM) specimens propagated as xenografts (PDX). Using a...
Abstract There is increasing interest in utilizing vitro cultures as patient avatars to develop personalized treatment for cancer. Typical utilize Matrigel-coated plates and media promote the proliferation of cancer cells spheroids or tumor explants. However, standard culture conditions operate large volumes require a high concentration initiate this process. Other limitations include variability ability successfully establish stable line inconsistency dimensions these microcancers vivo drug...
In high-grade serous ovarian carcinoma (HGSC), deleterious mutations in DNA repair gene RAD51C are established drivers of defective homologous recombination and emerging biomarkers PARP inhibitor (PARPi) sensitivity. promoter methylation (meRAD51C) is detected at similar frequencies to mutations, yet its effects on PARPi responses remain unresolved.In this study, three HGSC patient-derived xenograft (PDX) models with most or all examined CpG sites the show PARPi. Both complete heterogeneous...
Estrogens play a crucial role in the causation and development of sporadic human breast cancer (BC). Chromosomal instability (CIN) is defining trait early ductal carcinoma situ (DCIS) believed to precipitate oncogenesis. We reported earlier that 100% female ACI (August/Copenhagen/Irish) rats treated with essentially physiological serum levels 17β-estradiol lead mammary gland tumors histopathologic, cellular, molecular, ploidy changes remarkably similar those seen DCIS invasive BC. Aurora-A...
ObjectiveWe describe a phase II clinical trial of the combination ribociclib and letrozole for treatment relapsed oestrogen receptor (ER)-positive ovarian cancer (OC) endometrial (EC). The primary endpoint was proportion patients alive, progression-free survival (PFS), still on at 12 weeks (PFS12), with 45% or greater considered positive.MethodsPatients measurable, ER-positive OC EC (platinum-sensitive resistant) were eligible treated 400 mg oral 2.5 daily. Patient-derived xenografts (PDXs)...
Abstract In ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory poorer survival. We previously developed a vaccine whereby patient-derived dendritic (DCs) are programmed to induce Th17 responses the OC antigen folate receptor alpha (FRα). Here we report results of single-arm open-label phase I clinical trial designed determine safety and tolerability (primary outcomes) recurrence-free survival (secondary outcome). Immunogenicity is also...
Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors exhibit promising activity against ovarian cancers, but their efficacy can be limited by acquired drug resistance. This study explores the role of autophagy in regulating sensitivity cancer cells to PARP inhibitors.Induction was detected punctate LC3 fluorescence staining, LC3I LC3II conversion on Western blot analysis, and electron microscopy. Enhanced growth inhibition apoptosis were observed when used with hydroxychloroquine,...
Abstract Purpose: Clear cell ovarian carcinoma (CCOC) is an aggressive disease that often demonstrates resistance to standard chemotherapies. Approximately 25% of patients with CCOC show a strong APOBEC mutation signature. Here, we determine which APOBEC3 enzymes are expressed in CCOC, establish clinical correlates, and identify new biomarker for detection intervention. Experimental Designs: expression was analyzed by IHC qRT-PCR pilot set specimens (n = 9 tumors). The analysis APOBEC3B...
Dissemination of ovarian cancer cells can lead to inoperable metastatic lesions in the bowel and omentum that cause patient death. Here we show LRRC15, a type-I 15-leucine-rich repeat-containing membrane protein, highly overexpressed metastases compared with matched primary tumors acts as potent promoter omental metastasis. Complementary models demonstrated LRRC15 expression leads inhibition anoikis-induced cell death promotes adhesion invasion through matrices mimic omentum....
Resistance to platinum compounds is a major determinant of patient survival in high-grade serous ovarian cancer (HGSOC). To understand mechanisms resistance and identify potential therapeutic targets resistant HGSOC, we generated data resource composed dynamic (±carboplatin) protein, post-translational modification, RNA sequencing (RNA-seq) profiles from intra-patient cell line pairs derived 3 HGSOC patients before after acquiring resistance. These reveal extensive responses carboplatin that...
Interest in preclinical drug development for ovarian cancer has stimulated of patient-derived xenograft (PDX) or tumorgraft models. However, the unintended formation human lymphoma severe combined immunodeficiency (SCID) mice from Epstein-Barr virus (EBV)–infected lymphocytes can be problematic. In this study, we have characterized PDXs which developed lymphomas and explore methods to suppress lymphoproliferative growth. Fresh tumors 568 patients were transplanted intraperitoneally SCID...
E26 transformation-specific transcription factor ERG is aberrantly overexpressed in approximately 50% of all human prostate cancer due to
BRCA1 plays a key role in homologous recombination (HR) DNA repair. Accordingly, changes that downregulate BRCA1, including mutations and reduced transcription, due to promoter hypermethylation or loss of the transcriptional regulator CDK12, disrupt HR multiple cancers. In addition, has also been implicated regulation metabolism. Here, we show reducing expression, either by CDK12 depletion, led metabolic reprogramming ovarian cancer cells, causing decreased mitochondrial respiration ATP...
Abstract Although 70–80% of newly diagnosed ovarian cancer patients respond to first-line therapy, almost all relapse and five-year survival remains below 50%. One strategy increase is prolonging time by improving therapy response. However, no biomarker today can accurately predict individual response therapy. In this study, we present analytical prospective clinical validation a new test that utilizes primary patient tissue in 3D cell culture make patient-specific predictions prior...
Abstract Chemotherapy-induced cognitive impairment (CICI) is often reported as a neurotoxic side effect of chemotherapy. Although CICI has emerged significant medical problem, meaningful treatments are not currently available due to lack mechanistic understanding underlying pathophysiology. Using the platinum-based chemotherapy cisplatin model for CICI, we show here that suppresses nicotinamide adenine dinucleotide (NAD+) levels in adult female mouse brain vivo and human cortical neurons...
AB160 is a 160-nm nano-immunoconjugate consisting of nab-paclitaxel (ABX) nanoparticles noncovalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels VEGF. Preclinical data showed that resulted in greater tumor targeting and inhibition compared sequential treatment ABX then BEV. Given individual drug activity, we investigated the safety toxicity patients gynecologic cancers.