3428 results for "ovarian cancer"

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• A Phase 2 Study of Lamivudine in Patients with p53 Mutant Metastatic Colorectal Cancer

  This was an open-label, single-arm Phase II study of lamivudine in patients who had progressed on systemic therapy for advanced colorectal cancer with TP53 mutations. The phase II study had a two-stage design, with a target accrual of 20 evaluable patients for the first stage and a total of 32 patients for the whole study. The first 9 patients were treated with lamivudine at 150 mg PO bid continuously for 28-day cycles. Subsequent patients (10-32) received a higher dose of 600 mg PO bid continuously for 28-day cycles. Tumor assessments were performed every 8 weeks until documented disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) or drug intolerance. Whole genome sequencing (WGS) and total RNA-seq were performed on pre- and post- treatment biopsies on this trial.

  Study phs002833

• Molecular Basis of Neuroendocrine Prostate Cancer (Trento/Cornell/Broad 2015)

  A subset of advanced prostate cancers can progress from an androgen receptor (AR)-driven state to AR independence, often associated with low or absent AR expression and extensive neuroendocrine differentiation. Once neuroendocrine prostate cancer (NEPC) develops, patients typically demonstrate an aggressive clinical course and poor overall survival. Early diagnosis is important but remains challenging as the clinical and pathologic features associate with AR independence and NEPC are poorly defined. We performed whole exome sequencing of 114 metastatic tumors from 81 patients (35 with morphologic features of NEPC). Serial or synchronous samples were included to characterize heterogeneity and the transition from adenocarcinoma to NEPC. Computational analysis of clonality and allele specific quantification were performed using CLONET. Quantitative mRNA assessment including AR signaling genes and DNA methylation were evaluated in the context of genomic changes.

  Study phs000909

• Genomic Tumor Correlates of Clinical Outcomes Following Organ-Sparing Chemoradiation Therapy for Bladder Cancer

  Bladder preservation with trimodality therapy (TMT), consisting of transurethral tumor resection followed by chemoradiation, is an alternative to radical cystectomy for muscle-invasive bladder cancer (MIBC), but molecular determinants of response are poorly understood. Patients with cT2-T4aN0M0 MIBC treated with definitive-intent chemoradiation as part of TMT were retrospectively identified from a single institution between 1986-2015. Pre-treatment Formalin Fixed Paraffin Embedded (FFPE) tumors from 76 MIBC patients were subjected to whole exome sequencing (WES). Our integrated analysis yielded insights into molecular features associated with favorable long-term response to TMT, including alterations in DNA damage response genes. Of these, mutations in ERCC2, a DNA helicase in the nucleotide excision repair pathway, were significantly associated with improved long-term outcomes after TMT, particularly in patients who received concurrent cisplatin-based chemotherapy.

  Study phs003402

• Combined PDCD1, BRAF and MAP2K7 Inhibition in BRAFV600E Colorectal Cancer: A Phase 2 Trial

  In this study, we evaluated the clinical efficacy of combined PDCD1, BRAF, and MAP2K7 inhibition in metastatic BRAFV600E Colorectal Cancer (CRC) patients (NCT03668431). We performed bulk whole exome sequencing (WXS) and bulk RNA sequencing (RNA-Seq) in 35 pre-treatment tumor biopsies and matching germline for tumor mutational burden (TMB), BM1/BM2 transcriptional subtypes, and consensus molecular subtypes (CMS) analysis, which were previously reported to affect prognosis and response to therapy (PMIDs: 32047001, 27354468, and 26457756). Analysis of bulk data showed that TMB, BM1/BM2 subtypes, and CMS did not correlate with clinical response in this study. Analysis of single cell RNA sequencing (scRNA-Seq) data of tumor epithelial cells from 23 paired day 0 and day 15 tumor biopsies revealed greater induction of tumor cell-intrinsic immune programs and more complete MAPK inhibition in patients with better clinical outcome.

  Study phs003178

• Randomized Phase II 2 x 2 Factorial Trial of the Addition of Carboplatin +/- Bevacizumab to Neoadjuvant Weekly Paclitaxel Followed by Dose-Dense AC in Hormone Receptor-Poor/HER2-Negative Resectable Breast Cancer: DNA Sequencing

  This randomized phase II trial studies how well paclitaxel with or without carboplatin and/or bevacizumab followed by doxorubicin and cyclophosphamide works in treating patients with breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, carboplatin, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab may stop the growth of tumor cells by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. All participants in this study were female. RNA sequencing data from the same patients were published under phs001863. Subject aliases are the same in the two datasets.

  Study phs003801

• P4HA1 Mediates Hypoxia-Induced Invasion in Human Pancreatic Cancer Organoids

  Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy defined by extensive invasion into the local tumor microenvironment and systemic metastasis. PDAC develops in a hypoxic microenvironment and adapts to survive under low oxygen conditions, including the activation of processes that may enhance the ability of cancer cells to invade locally or metastasize. Here we employ bulk RNA-sequencing of eight patient-derived organoid (PDO) cultures grown in hypoxia and normoxia to identify differentially expressed genes. PDOs were grown in Matrigel, transferred into collagen domes, then incubated in hypoxia or normoxia. Invasive organoids were individually collected from collagen domes grown in hypoxia and normoxia separately and processed for RNA-sequencing analysis. Using this dataset, prolyl 4-hydroxylase subunit alpha (P4HA1) was identified as a potential regulator of PDAC invasion in hypoxia. This dataset exists as a reference for gene expression of invasive organoids in hypoxia and normoxia.

  Study phs003961

• Epigenomics of Neurocognitive Function in Breast Cancer

  This study harnessed the data and biospecimens from the Exercise Program in Cancer and Cognition (EPICC) study (parent study) that collected data on cognitive function, demographics, other symptoms and biospecimens at two time points (T1: enrollment, T2: six months later) within the context of a six-month randomized controlled trial of a moderate intensity aerobic exercise intervention. This study collected genome wide DNA methylation data from T1 and T2 and conducted epigenome-wide association-based analyses to find genes and biological pathways explaining variability in cognitive function and explaining how exercise mitigates cognitive decline. Our initial findings identified cg10331779 near CTNND2 (p-value=9.65×10-9) associated with processing speed and cg25906741 in MLIP (p-value=2.01×10-8) associated with subjectively measured cognitive function. Additionally, differentially methylated regions were identified near SLC6A11, PRKG1/CSTF2T, and FAM3B for processing speed and near PI4KB and SGCE/PEG10 for mental flexibility.

  Study phs003959

• TRACERx: TRAcking non-small cell lung Cancer Evolution through therapy (Rx). Pilot Study. Multi-region sequencing of early-stage NSCLCs.

  Deciphering the complexity of non-small cell lung cancer (NSCLC) evolutionary histories may elucidate the basis for its dismal outcome. We performed multi-region sequencing of early-stage NSCLCs. Spatial dissection revealed branched tumor evolution, with driver mutations occurring before and after subclonal diversification. Intra-tumor heterogeneity in DNA copy number alterations, translocations and endogenous APOBEC mutational processes demonstrates that NSCLC may follow multiple distinct evolutionary trajectories simultaneously. In smokers, despite maintained carcinogen exposure, temporal dissection reveals a relative decrease in smoking-related mutations during tumor progression, accompanied by an increase in APOBEC-related mutations. In the tumors from ex-smokers, genome-doubling occurred before subclonal diversification, suggesting prolonged latency before clinical detection. Multi-region sequencing demonstrates the relentless and heterogeneous nature of genomic instability processes in early-stage NSCLCs.

  Study EGAS00001000809

• Evolutionary analysis of pancreatic cancer and coexistent precursor lesions using whole exome sequencing data

  Most adult carcinomas develop from noninvasive precursor lesions, a progression that is supported by genetic analysis. Further, the evolution of these lesions contextualizes the dynamics of advanced stage disease. We analyzed the somatic variants of co-existing pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas. After inferring evolutionary relationships, we found that the ancestral cell had initiated and clonally expanded to form one or more lesions, and that subsequent driver gene mutations eventually led to a pancreatic cancer. We also found that this multi-step progression generally spans many years. Our data suggest that independent, high-grade pancreatic lesions observed in a histologic cross section often represent a single neoplasm that can spread and colonize the ductal system, accumulating spatial and genetic divergence over time.

  Study EGAS00001002778

• Whole genome characterisation of lung cancer organoids and tissue

  Organoids are self-organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here we describe a method to establish long-term expanding human airway organoids from broncho-alveolar biopsies or lavage material. The pseudostratified airway organoid epithelium consists of basal cells, functional multi-ciliated cells, mucus-producing goblet cells, and CC10-secreting club cells. Airway organoids derived from cystic fibrosis (CF) patients allow assessment of CFTR function in an organoid swelling assay. Organoid culture conditions also allow gene editing as well as the derivation of various types of lung cancer organoids. Respiratory syncytial virus (RSV) infection recapitulated central disease features and dramatically increases organoid cell motility, found to be driven by the non-structural viral NS2 protein. We conclude that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease.

  Study EGAS00001002899