Journal ArticleMatrix Biol · April 2025
Collagen stroma interactions within the extracellular microenvironment of breast tissue play a significant role in breast cancer, including risk, progression, and outcomes. Hydroxylation of proline (HYP) is a common post-translational modification directly ...
Full textLink to itemCite
Journal ArticleBreast Cancer Res · March 21, 2025
BACKGROUND: Progression from pre-cancers like ductal carcinoma in situ (DCIS) to invasive disease (cancer) is driven by somatic evolution and is altered by clinical interventions. We hypothesized that genetic and/or phenotypic intra-tumor heterogeneity wou ...
Full textLink to itemCite
Journal ArticleJAMA · March 2025
ImportanceActive monitoring for low-risk ductal carcinoma in situ (DCIS) of the breast has been proposed as an alternative to guideline-concordant care, but the safety of this approach is unknown.ObjectiveTo compare rates of invasive canc ...
Full textCite
Journal ArticleBreast Cancer Res · February 20, 2025
PURPOSE: CALGB 40903 (Alliance) was a phase II single arm multicenter trial conducted in postmenopausal patients diagnosed with estrogen-receptor (ER) positive breast ductal carcinoma in situ (DCIS) without invasion. Patients were treated with the aromatas ...
Full textLink to itemCite
Journal ArticleCancer · January 1, 2025
BACKGROUND: Black women with epithelial ovarian cancer (EOC) have worse survival and a higher burden of comorbid conditions compared with other racial groups. This study examines the association of comorbid conditions and medication use for these condition ...
Full textLink to itemCite
Journal ArticleAnn Epidemiol · November 2024
BACKGROUND: Mediation by multiple agents can affect the relation between neighborhood deprivation and segregation indices and ovarian cancer survival. In this paper, we examine a variety of potential clinical mediators in the association between deprivatio ...
Full textLink to itemCite
Journal ArticleJAMA network open · October 2024
ImportanceOvarian cancer survival among Black women is the lowest across all racial and ethnic groups. Poor dietary quality also disproportionately affects Black populations, but its association with ovarian cancer survival in this population rema ...
Full textCite
Journal ArticleBreast Cancer Res · September 2, 2024
BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer (IBC). Studies have indicated differences in DCIS outcome based on race or ethnicity, but molecular differences have not been investigated. METHODS: We examin ...
Full textLink to itemCite
Journal ArticleCancer Epidemiol Biomarkers Prev · August 1, 2024
BACKGROUND: High-grade serous carcinoma (HGSC) gene expression subtypes are associated with differential survival. We characterized HGSC gene expression in Black individuals and considered whether gene expression differences by self-identified race may con ...
Full textLink to itemCite
Journal ArticleInt J Mol Sci · June 19, 2024
Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) ...
Full textLink to itemCite
Journal ArticleAm J Hum Genet · June 6, 2024
To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 contro ...
Full textLink to itemCite
Journal ArticlePLoS One · 2024
OBJECTIVES: To assess the performance bias caused by sampling data into training and test sets in a mammography radiomics study. METHODS: Mammograms from 700 women were used to study upstaging of ductal carcinoma in situ. The dataset was repeatedly shuffle ...
Full textLink to itemCite
Journal ArticleCancers (Basel) · October 4, 2023
BACKGROUND: Deprivation indices are often used to adjust for socio-economic disparities in health studies. Their role has been partially evaluated for certain population-level cancer outcomes, but examination of their role in ovarian cancer is limited. In ...
Full textLink to itemCite
Journal ArticleIEEE Trans Med Imaging · October 2023
Computer-aided detection (CAD) frameworks for breast cancer screening have been researched for several decades. Early adoption of deep-learning models in CAD frameworks has shown greatly improved detection performance compared to traditional CAD on single- ...
Full textLink to itemCite
Journal ArticleAnn Epidemiol · October 2023
PURPOSE: Deprivation and segregation indices are often examined as possible explanations for observed health disparities in population-based studies. In this study, we assessed the role of recognized deprivation and segregation indices specifically as they ...
Full textLink to itemCite
Journal ArticleBritish journal of cancer · October 2023
BackgroundAn association was observed between an inflammation-related risk score (IRRS) and worse overall survival (OS) among a cohort of mostly White women with invasive epithelial ovarian cancer (EOC). Herein, we evaluated the association betwee ...
Full textCite
Journal ArticleCell · August 2023
Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embed ...
Full textCite
Journal ArticleSci Rep · June 8, 2023
Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. T ...
Full textLink to itemCite
Journal ArticleCancer Causes Control · March 2023
PURPOSE: The causes for the survival disparity among Black women with epithelial ovarian cancer (EOC) are likely multi-factorial. Here we describe the African American Cancer Epidemiology Study (AACES), the largest cohort of Black women with EOC. METHODS: ...
Full textLink to itemCite
Journal ArticleBiomaterials · January 2023
Intraperitoneal adhesions (IAs) are a major complication arising from abdominal repair surgeries, including hernia repair procedures. Herein, we fabricated a composite mesh device using a macroporous monofilament polypropylene mesh and a degradable elastom ...
Full textLink to itemCite
Journal ArticleCancer Cell · December 12, 2022
Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical outcomes by analyzing 774 DCIS samples from ...
Full textLink to itemCite
Journal ArticleNPJ Breast Cancer · September 15, 2022
Hypoxia promotes aggressive tumor phenotypes and mediates the recruitment of suppressive T cells in invasive breast carcinomas. We investigated the role of hypoxia in relation to T-cell regulation in ductal carcinoma in situ (DCIS). We designed a deep lear ...
Full textLink to itemCite
Journal ArticleNat Genet · June 2022
Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5-10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease aris ...
Full textLink to itemCite
Journal ArticleCancer Epidemiol Biomarkers Prev · May 4, 2022
BACKGROUND: Tumor-infiltrating lymphocytes (TIL) confer a survival benefit among patients with ovarian cancer; however, little work has been conducted in racially diverse cohorts. METHODS: The current study investigated racial differences in the tumor immu ...
Full textLink to itemCite
Journal ArticleIEEE Trans Biomed Eng · May 2022
In mammography, calcifications are one of the most common signs of breast cancer. Detection of such lesions is an active area of research for computer-aided diagnosis and machine learning algorithms. Due to limited numbers of positive cases, many supervise ...
Full textLink to itemCite
Journal ArticleAnalyst · April 11, 2022
Ductal carcinoma in situ (DCIS) is frequently associated with breast calcification. This study combines multiple analytical techniques to investigate the heterogeneity of these calcifications at the micrometre scale. X-ray diffraction, scanning electron mi ...
Full textLink to itemCite
Journal ArticleRadiology · April 2022
Background Improving diagnosis of ductal carcinoma in situ (DCIS) before surgery is important in choosing optimal patient management strategies. However, patients may harbor occult invasive disease not detected until definitive surgery. Purpose To assess t ...
Full textCite
Journal ArticleEuropean journal of human genetics : EJHG · March 2022
Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of P ...
Full textCite
Journal ArticleCell · January 20, 2022
Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor to invasive breast cancer (IBC). To understand the changes in the tumor microenvironment (TME) accompanying transition to IBC, we used multiplexed ion beam imaging b ...
Full textLink to itemCite
ConferenceCancer Epidemiology, Biomarkers & Prevention · January 1, 2022
AbstractA survival benefit has been consistently observed for tumor infiltrating lymphocytes (TILs) among ovarian cancer patients; however, prior studies consist of predominantly white women and little work ...
Full textCite
ConferenceProceedings - International Symposium on Biomedical Imaging · January 1, 2022
Ductal Carcinoma In Situ (DCIS) is a non-obligatory precursor of Invasive Breast Cancer. It is the most common mammographically detected breast cancer. Predicting DCIS progression to invasive ductal carcinoma is a major clinical challenge due to the lack o ...
Full textCite
ConferenceLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) · January 1, 2022
Tumour infiltrating lymphocytes (TIL) influence the prognosis of Ductal carcinoma in situ (DCIS). Currently, manual assessment of TIL by expert pathologists is considered a gold standard. However, there are issues with a shortage of expert pathologists and ...
Full textCite
Conferencenpj Breast Cancer · December 1, 2021
Despite increasing evidence supporting the clinical relevance of tumour infiltrating lymphocytes (TILs) in invasive breast cancer, TIL spatial variability within ductal carcinoma in situ (DCIS) samples and its association with progression are not well unde ...
Full textCite
Journal Articlenpj Breast Cancer · December 1, 2021
B cell responses to tumor antigens occur early in breast tumors and may identify immunogenic drivers of tumorigenesis. Sixty-two candidate antigens were identified prior to palpable tumor development in TgMMTV-neu and C3(1)Tag transgenic mouse mammary tumo ...
Full textCite
Journal ArticleBriefings in bioinformatics · November 2021
Most tissue collections of neoplasms are composed of formalin-fixed and paraffin-embedded (FFPE) excised tumor samples used for routine diagnostics. DNA sequencing is becoming increasingly important in cancer research and clinical management; however it is ...
Full textCite
Journal ArticleNPJ Breast Cancer · March 1, 2021
Despite increasing evidence supporting the clinical relevance of tumour infiltrating lymphocytes (TILs) in invasive breast cancer, TIL spatial variability within ductal carcinoma in situ (DCIS) samples and its association with progression are not well unde ...
Full textOpen AccessLink to itemCite
ConferenceLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) · January 1, 2021
In mammography and tomosynthesis, radiologists use the geometric relationship of the four standard screening views to detect breast abnormalities. To date, computer aided detection methods focus on formulations based only on a single view. Recent multi-vie ...
Full textCite
Journal ArticleNat Commun · November 30, 2020
Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20128-w. ...
Full textLink to itemCite
ConferenceCancer Research · August 15, 2020
AbstractGenetic diversity both between and within individual tumors constitutes a challenge to personalized cancer medicine. Intra-tumor heterogeneity provides the genetic fuel for natural selection in clona ...
Full textCite
Journal ArticleCell Death Differ · July 2020
The molecular and genetic basis of tumor recurrence is complex and poorly understood. RIPK3 is a key effector in programmed necrotic cell death and, therefore, its expression is frequently suppressed in primary tumors. In a transcriptome profiling between ...
Full textLink to itemCite
Journal ArticleIEEE Trans Biomed Eng · June 2020
OBJECTIVE: The goal of this study is to use adjunctive classes to improve a predictive model whose performance is limited by the common problems of small numbers of primary cases, high feature dimensionality, and poor class separability. Specifically, our ...
Full textLink to itemCite
Journal ArticleJ Clin Oncol · April 20, 2020
PURPOSE: Primary endocrine therapy for ductal carcinoma in situ (DCIS) as a potential alternative to surgery has been understudied. This trial explored the feasibility of a short-term course of letrozole and sought to determine whether treatment results in ...
Full textLink to itemCite
Journal ArticleCell · April 16, 2020
Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial mu ...
Full textOpen AccessLink to itemCite
Journal ArticleNature communications · March 2020
Intra-tumoral heterogeneity (ITH) could represent clonal evolution where subclones with greater fitness confer more malignant phenotypes and invasion constitutes an evolutionary bottleneck. Alternatively, ITH could represent branching evolution with invasi ...
Full textCite
ConferenceCancer Research · February 15, 2020
AbstractBackground: Guideline-concordant care (GCC) for DCIS includes surgery, radiation, and endocrine treatment. Active surveillance (AS) is a strategy under study for management of low risk DCIS. The PORT ...
Full textCite
ConferenceCancer Research · February 15, 2020
AbstractAlthough European American women have a higher incidence of breast cancer, African American women have higher mortality rates with increased occurrence of lethal cancers at a younger age. Breast dens ...
Full textCite
Journal ArticleNature · February 2020
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1-3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matchin ...
Full textLink to itemCite
Journal ArticleNPJ breast cancer · January 2020
We lack tools to risk-stratify triple-negative breast cancer (TNBC). Our goal was to develop molecular tools to predict disease recurrence. Methylation array analysis was performed on 110 samples treated by locoregional therapy obtained from institutional ...
Full textCite
ConferenceProgress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2020
Detecting microcalcification clusters in mammograms is important to the diagnosis of breast diseases. Previous studies which mainly focused on supervised methods require abundant annotated training data but these data are usually hard to acquire. In this w ...
Full textCite
ConferenceProgress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2020
We proposed a two-branch multitask learning convolutional neural network to solve two different but related tasks at the same time. Our main task is to predict occult invasive disease in biopsy proven Ductal Carcinoma in-situ (DCIS), with an auxiliary task ...
Full textCite
Journal ArticleCell reports · October 2019
Notwithstanding the positive clinical impact of endocrine therapies in estrogen receptor-alpha (ERα)-positive breast cancer, de novo and acquired resistance limits the therapeutic lifespan of existing drugs. Taking the position that resistance is nearly in ...
Full textCite
Journal ArticleNat Immunol · July 2019
How tumor cells genetically lose antigenicity and evade immune checkpoints remains largely elusive. We report that tissue-specific expression of the human long noncoding RNA LINK-A in mouse mammary glands initiates metastatic mammary gland tumors, which ph ...
Full textLink to itemCite
Journal ArticleJ Magn Reson Imaging · June 2019
BACKGROUND: While important in diagnosis of breast cancer, the scientific assessment of the role of imaging in prognosis of outcomes and treatment planning is limited. PURPOSE: To evaluate the potential of using quantitative imaging variables for stratifyi ...
Full textLink to itemCite
Journal ArticleCell Res · April 2019
Despite the structural conservation of PTEN with dual-specificity phosphatases, there have been no reports regarding the regulatory mechanisms that underlie this potential dual-phosphatase activity. Here, we report that K27-linked polyubiquitination of PTE ...
Full textLink to itemCite
ConferenceCancer Research · February 15, 2019
AbstractBackground: Heterogeneity is a hallmark of human cancers that is apparent both between and within individual tumors. Intra-tumor heterogeneity provides the genetic fuel for natural selection in clona ...
Full textCite
Journal ArticleBreast Cancer Res Treat · January 2019
PURPOSE: To determine whether a multivariate machine learning-based model using computer-extracted features of pre-treatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can predict pathologic complete response (pCR) to neoadjuvant therap ...
Full textLink to itemCite
ConferenceProgress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2019
Annotated data availability has always been a major limiting f actor for the development of algorithms in the field of computer aided diagnosis. The purpose of this study is to investigate the feasibility of using a conditional generative adversarial netwo ...
Full textCite
Journal ArticleProgress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2019
Detection and localization of microcalcification (MC) clusters are very important in mammography diagnosis. Supervised MC detectors require learning from extracted individual MCs and MC clusters. However, they are limited by number of datasets given that M ...
Full textCite
ConferenceProgress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2019
Detection of suspicious breast cancer lesion in screening mammography images is an important step for the downstream diagnosis the of breast cancer. A trained radiologist can usually take advantage of multi-view correlation of suspicious lesions to locate ...
Full textCite
ConferenceLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) · January 1, 2019
Generative Adversarial Networks (GANs) have found applications in natural image synthesis and begin to show promises generating synthetic medical images. In many cases, the ability to perform controlled image synthesis using masked priors such as shape and ...
Full textCite
Journal ArticleBreast Cancer Res Treat · November 2018
PURPOSE: The purpose of the study was to define quantitative measures of intra-tumor heterogeneity in breast cancer based on histopathology data gathered from multiple samples on individual patients and determine their association with distant recurrence-f ...
Full textLink to itemCite
Journal ArticleCell Rep · October 30, 2018
Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional "omic" data from The Cancer Genom ...
Full textLink to itemCite
Journal ArticleCell Syst · October 24, 2018
We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and re ...
Full textLink to itemCite
Journal ArticleMol Cell · October 4, 2018
Cancer cells entail metabolic adaptation and microenvironmental remodeling to survive and progress. Both calcium (Ca2+) flux and Ca2+-dependent signaling play a crucial role in this process, although the underlying mechanism has yet to be elucidated. Throu ...
Full textLink to itemCite
Journal ArticleCancer Lett · August 28, 2018
As a class of endogenous noncoding RNAs, circular RNAs (circRNAs) have been recently identified to regulate tumourigenesis and progression in multiple malignancies. However, the expression profiles and function of circRNAs in breast cancer metastasis are l ...
Full textLink to itemCite
Journal ArticleCancer Res · August 15, 2018
Long noncoding RNA (lncRNA) is yet to be linked to cancer metabolism. Here, we report that upregulation of the lncRNA LINC00538 (YIYA) promotes glycolysis, cell proliferation, and tumor growth in breast cancer. YIYA is associated with the cytosolic cyclin- ...
Full textLink to itemCite
Journal ArticleCancer Cell · August 13, 2018
Our comprehensive analysis of alternative splicing across 32 The Cancer Genome Atlas cancer types from 8,705 patients detects alternative splicing events and tumor variants by reanalyzing RNA and whole-exome sequencing data. Tumors have up to 30% more alte ...
Full textLink to itemCite
ConferenceCancer Research · July 1, 2018
AbstractOvarian cancer is the most lethal gynecologic cancer in the United States, and African-American (AA) women have the poorest outcomes compared to other racial/ethnic groups. Although several biomarker ...
Full textCite
Journal ArticleCancer cell · April 2018
We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and c ...
Full textCite
Journal ArticleCell reports · April 2018
Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, includ ...
Full textCite
Journal ArticleCell reports · April 2018
Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling th ...
Full textCite
Journal ArticleCell reports · April 2018
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation ra ...
Full textCite
Journal ArticleCell · April 2018
The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we pr ...
Full textCite
Journal ArticleCell · April 2018
We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chr ...
Full textCite
Journal ArticleCell reports · April 2018
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumor-infiltrating lymphocytes (TILs) based on H&E images from 13 TCGA t ...
Full textCite
Journal ArticleCell · April 2018
We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including ...
Full textCite
Journal ArticleCell reports · April 2018
Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabo ...
Full textCite
Journal ArticleCell reports · April 2018
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recu ...
Full textCite
Journal ArticleImmunity · April 2018
We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyt ...
Full textCite
Journal ArticleCell reports · April 2018
Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atla ...
Full textCite
Journal ArticleCell reports · April 2018
Precision oncology uses genomic evidence to match patients with treatment but often fails to identify all patients who may respond. The transcriptome of these "hidden responders" may reveal responsive molecular states. We describe and evaluate a machine-le ...
Full textCite
Journal ArticleCancer cell · April 2018
We characterized the epigenetic landscape of genes encoding long noncoding RNAs (lncRNAs) across 6,475 tumors and 455 cancer cell lines. In stark contrast to the CpG island hypermethylation phenotype in cancer, we observed a recurrent hypomethylation of 1, ...
Full textCite
Journal ArticleCell · April 2018
The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number of expressed enhancers in a genome-wide analysis of 892 ...
Full textCite
Journal ArticleCell · April 2018
Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tu ...
Full textCite
Journal ArticleCell · April 2018
Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one ...
Full textCite
Journal ArticleCell · April 2018
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features represe ...
Full textCite
Journal ArticleCancer cell · April 2018
Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression of pro ...
Full textCite
Journal ArticleCancer cell · April 2018
We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We f ...
Full textCite
Journal ArticleCell · April 2018
Identifying molecular cancer drivers is critical for precision oncology. Multiple advanced algorithms to identify drivers now exist, but systematic attempts to combine and optimize them on large datasets are few. We report a PanCancer and PanSoftware analy ...
Full textCite
Journal ArticleCell reports · April 2018
Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome ...
Full textCite
Journal ArticleCell reports · April 2018
For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creat ...
Full textCite
Journal ArticleCell reports · April 2018
DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heter ...
Full textCite
Journal ArticleCell Syst · March 28, 2018
Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational ...
Full textLink to itemCite
Journal ArticleJ Am Coll Radiol · March 2018
PURPOSE: The aim of this study was to determine whether deep features extracted from digital mammograms using a pretrained deep convolutional neural network are prognostic of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core ...
Full textLink to itemCite
Journal ArticleCell systems · March 2018
The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor-normal exome pairs across 33 different cancer types, in total >400 TB of raw data files requiring analysis. Here we describe the Multi-Center Mutation Calling in Multiple Can ...
Full textCite
ConferenceProgress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2018
Purpose: To determine whether domain transfer learning can improve the performance of deep features extracted from digital mammograms using a pre-trained deep convolutional neural network (CNN) in the prediction of occult invasive disease for patients with ...
Full textCite
ConferenceProgress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2018
Predicting whether ductal carcinoma in situ (DCIS) identified at core biopsy contains occult invasive disease is an import task since these "upstaged" cases will affect further treatment planning. Therefore, a prediction model that better classifies pure D ...
Full textCite
Journal ArticleJ Clin Invest · December 1, 2017
Conventional therapies for breast cancer brain metastases (BCBMs) have been largely ineffective because of chemoresistance and impermeability of the blood-brain barrier. A comprehensive understanding of the underlying mechanism that allows breast cancer ce ...
Full textLink to itemCite
Journal ArticleEMBO J · November 15, 2017
The Hippo pathway plays essential roles in organ size control and cancer prevention via restricting its downstream effector, Yes-associated protein (YAP). Previous studies have revealed an oncogenic function of YAP in reprogramming glucose metabolism, whil ...
Full textLink to itemCite
Journal ArticleJ Magn Reson Imaging · November 2017
PURPOSE: To assess the ability of algorithmically assessed magnetic resonance imaging (MRI) features to predict the likelihood of upstaging to invasive cancer in newly diagnosed ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: We identified 131 pati ...
Full textLink to itemCite
Journal ArticleAcad Radiol · September 2017
RATIONALE AND OBJECTIVES: This study aimed to determine whether mammographic features assessed by radiologists and using computer algorithms are prognostic of occult invasive disease for patients showing ductal carcinoma in situ (DCIS) only in core biopsy. ...
Full textLink to itemCite
Journal ArticleEMBO J · August 1, 2017
O-GlcNAcylation is an essential, nutrient-sensitive post-translational modification, but its biochemical and phenotypic effects remain incompletely understood. To address this question, we investigated the global transcriptional response to perturbations i ...
Full textOpen AccessLink to itemCite
Journal ArticleNat Cell Biol · March 2017
Phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3 or PIP3) mediates signalling pathways as a second messenger in response to extracellular signals. Although primordial functions of phospholipids and RNAs have been hypothesized in the 'RNA world', p ...
Full textLink to itemCite
ConferenceCancer Research · February 15, 2017
AbstractPurpose: Intratumoral heterogeneity is well recognized to be an important driver of treatment resistance and metastasis. We undertook this N of one study to measure the degree of heterogeneity in a s ...
Full textCite
ConferenceCancer Research · February 15, 2017
AbstractIntra-tumor heterogeneity drives neoplastic progression by supplying the fuel for natural selection among neoplastic cells. It also complicates screening and treatment of neoplasms. We hypothesize th ...
Full textCite
Journal ArticleBreast Cancer Res Treat · February 2017
PURPOSE: Given the potential savings in cost and resource utilization, several algorithms have been proposed to predict Oncotype DX recurrence score (ODX RS) using commonly acquired histopathologic variables. Although it is promising, additional independen ...
Full textLink to itemCite
ConferenceProgress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2017
Predicting the risk of occult invasive disease in ductal carcinoma in situ (DCIS) is an important task to help address the overdiagnosis and overtreatment problems associated with breast cancer. In this work, we investigated the feasibility of using comput ...
Full textCite
ConferenceProgress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2017
Reducing the overdiagnosis and overtreatment associated with ductal carcinoma in situ (DCIS) requires accurate prediction of the invasive potential at cancer screening. In this work, we investigated the utility of pre-operative histologic and mammographic ...
Full textCite
ConferenceProgress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2017
Medical oncologists increasingly rely on expensive genomic analysis to stratify patients for different treatment. The genomic markers are able to divide patients into groups that behave differently in terms of tumor presentation, likelihood of metastatic s ...
Full textCite
Journal ArticleJ Med Genet · December 2016
BACKGROUND: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk ...
Full textLink to itemCite
ConferenceCancer Research · July 15, 2016
AbstractOvarian cancer accounts for 5% of cancer deaths and is the fifth leading cause of cancer death in women in the United States. While incidence is higher in European American (EA) than African American ...
Full textCite
Journal ArticleCancer Epidemiol Biomarkers Prev · July 2016
BACKGROUND: Blood-based testing can be used as a noninvasive method to recover and analyze circulating tumor-derived cells for clinical use. Circulating cancer-associated macrophage-like cells (CAML) are specialized myeloid cells found in peripheral blood ...
Full textLink to itemCite
Journal ArticleJ Natl Cancer Inst · May 2016
BACKGROUND: Ductal carcinoma in situ (DCIS) is a noninvasive breast lesion with uncertain risk for invasive progression. Usual care (UC) for DCIS consists of treatment upon diagnosis, thus potentially overtreating patients with low propensity for progressi ...
Full textLink to itemCite
Journal ArticleMol Syst Biol · March 10, 2016
The signaling events that drive familial breast cancer (FBC) risk remain poorly understood. While the majority of genomic studies have focused on genetic risk variants, known risk variants account for at most 30% of FBC cases. Considering that multiple gen ...
Full textLink to itemCite
ConferenceCancer Research · February 15, 2016
AbstractBackground: Breast cancer (BC) remains the second leading cause of cancer-related deaths for women in the United States and is recognized to be a heterogeneous disease. Advances in technologies such ...
Full textCite
ConferenceCancer Research · February 15, 2016
AbstractBackground: Recent evidence indicates that breast cancers may have high levels of heterogeneity. Based on principles of tumor evolution, we are investigating whether DCIS with higher levels of intra- ...
Full textCite
Journal ArticleNature cell biology · February 2016
Although long non-coding RNAs (lncRNAs) predominately reside in the nucleus and exert their functions in many biological processes, their potential involvement in cytoplasmic signal transduction remains unexplored. Here, we identify a cytoplasmic lncRNA, L ...
Full textCite
Journal ArticleCarcinogenesis · November 2015
Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide poly ...
Full textLink to itemCite
Journal ArticleCell · October 8, 2015
Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best kn ...
Full textLink to itemCite
Journal ArticleBreast Cancer Res · September 17, 2015
INTRODUCTION: There are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of patients. We profiled the temporal molecular changes during DCIS ...
Full textLink to itemCite
Journal ArticleCancer Epidemiol Biomarkers Prev · February 2015
BACKGROUND: Many circulating biomarkers have been reported for the diagnosis of breast cancer, but few, if any, have undergone rigorous credentialing using prospective cohorts and blinded evaluation. METHODS: The NCI Early Detection Research Network (EDRN) ...
Full textLink to itemCite
Journal ArticleBreast Cancer Res · August 5, 2014
INTRODUCTION: Remodeling of cellular metabolism appears to be a consequence and possibly a cause of oncogenic transformation in human cancers. Specific aspects of altered tumor metabolism may be amenable to therapeutic intervention and could be coordinated ...
Full textLink to itemCite
Journal ArticleBreast Cancer Res · December 5, 2013
The BRCA1 hereditary susceptibility gene has been studied in great depth, befitting its clear role in promoting basal type breast cancer and serous type ovarian (fallopian tube) cancer in women carrying germline mutations. The BRCA1 protein has long been i ...
Full textLink to itemCite
Journal ArticleCancer Epidemiol Biomarkers Prev · October 2013
BACKGROUND: Six gene expression subtypes of invasive epithelial ovarian cancer were recently defined using microarrays by Tothill and colleagues. The Cancer Genome Atlas (TCGA) project subsequently replicated these subtypes and identified a signature predi ...
Full textLink to itemCite
Journal ArticleGynecol Oncol · April 2013
OBJECTIVE: Polymorphisms in the vitamin D receptor (VDR) gene have been shown in some studies to be associated with the risk of epithelial ovarian cancer (EOC) in Caucasian women. There are no published reports among African Americans. METHODS: Case-contro ...
Full textLink to itemCite
Journal ArticleCancer Biomark · 2013
BACKGROUND: Post-translational protein modifications (PTMs) are increased in breast tumors. OBJECTIVE: We explored whether PTMs on proteins secreted by the breast could be detected in plasma and potentially used for the early detection of breast cancer. ME ...
Full textLink to itemCite
Journal ArticleNature · October 4, 2012
We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights ...
Full textLink to itemCite
Journal ArticleInt J Gynecol Cancer · January 2012
BACKGROUND: Inactivating somatic mutations in the ARID1A gene are described in a significant fraction of clear cell and endometrioid ovarian cancers leading to loss of the corresponding protein (BAF250a). Expression of BAF250a was examined in clear cell an ...
Full textLink to itemCite
Journal ArticleCancer Res · October 1, 2011
To better understand the biology of hormone receptor-positive and-negative breast cancer and to identify methylated gene markers of disease progression, we carried out a genome-wide methylation array analysis on 103 primary invasive breast cancers and 21 n ...
Full textLink to itemCite
Journal ArticlePLoS Genet · August 2011
Although significant variations in the metabolic profiles exist among different cells, little is understood in terms of genetic regulations of such cell type-specific metabolic phenotypes and nutrient requirements. While many cancer cells depend on exogeno ...
Full textLink to itemCite
Journal ArticleBiochem Pharmacol · July 15, 2011
It has become apparent of late that even in tamoxifen and/or aromatase resistant breast cancers, ERα remains a bona fide therapeutic target. Not surprisingly, therefore, there has been considerable interest in developing Selective ER Degraders (SERDs), com ...
Full textLink to itemCite
Journal ArticleCancer Epidemiol Biomarkers Prev · July 2011
BACKGROUND: Current biomarkers for breast cancer have little potential for detection. We determined whether breast cancer subtypes influence circulating protein biomarkers. METHODS: A sandwich ELISA microarray platform was used to evaluate 23 candidate bio ...
Full textLink to itemCite
Journal ArticleBreast Cancer Res · June 7, 2011
INTRODUCTION: Breast cancer heterogeneity occurs as a consequence of the dysregulation of numerous oncogenic pathways as well as many non-genetic factors, including tumor microenvironmental stresses such as hypoxia, lactic acidosis, and glucose deprivation ...
Full textLink to itemCite
Journal ArticleMol Endocrinol · May 2011
The molecular mechanisms responsible for aberrant calcium signaling in parathyroid disease are poorly understood. The loss of appropriate calcium-responsive modulation of PTH secretion observed in parathyroid disease is commonly attributed to decreased exp ...
Full textLink to itemCite
ConferenceCancer Research · April 15, 2011
AbstractPost-translational modifications (PTMs) of proteins are known to be altered during breast cancer development. These PTMs are potentially useful biomarkers for breast cancer. In order to study the pot ...
Full textCite
Journal ArticleCancer · February 1, 2011
BACKGROUND: Pathologic and genetic data suggest that epithelial ovarian cancer may consist of indolent and aggressive phenotypes. The objective of the current study was to estimate the impact of a 2-phenotype paradigm of epithelial ovarian cancer on the mo ...
Full textLink to itemCite
Journal ArticleInt J Cancer · January 15, 2011
Abnormal DNA methylation is a feature of most types of cancer, which is reflected in cell-free circulating DNA in plasma. It is, however, unknown whether surgical removal of the tumor and subsequent therapy induces changes in plasma DNA methylation, which ...
Full textLink to itemCite
Journal ArticleJ Proteome Res · January 7, 2011
Cancer patients spontaneously generate autoantibodies (AAb) to tumor-derived proteins. To detect AAb, we have probed novel high-density custom protein microarrays (NAPPA) expressing 4988 candidate tumor antigens with sera from patients with early stage bre ...
Full textLink to itemCite
Journal ArticleBreast Cancer Res Treat · January 2011
Differences in redox homeostatic control between cancer patients may underlie predisposition to drug resistance and toxicities. To evaluate interindividual differences in redox response among newly diagnosed breast cancer patients undergoing standard chemo ...
Full textLink to itemCite
Journal ArticleBreast Cancer Res Treat · November 2010
The incomplete penetrance of mutations in BRCA1 and BRCA2 suggests that some combination of environmental and genetic factors modifies the risk of breast cancer in mutation carriers. This study sought to identify possible interactions between established b ...
Full textLink to itemCite
Journal ArticleJ Clin Endocrinol Metab · November 2010
CONTEXT: A relationship between primary hyperparathyroidism (PHPT) and obesity has been observed but is incompletely understood. Furthermore, obesity has been associated with vitamin D deficiency, suggesting that the three conditions may be linked. OBJECTI ...
Full textLink to itemCite
Journal ArticleCancer Epidemiol Biomarkers Prev · June 2010
BACKGROUND: We used doxorubicin-based chemotherapy as a clinical model of oxidative assault in humans. METHODS: The study recruited newly diagnosed breast cancer patients (n = 23). Urine samples were collected immediately before (T0) and at 1 hour (T1) and ...
Full textLink to itemCite
Journal ArticleBMC Cancer · May 26, 2010
BACKGROUND: Mutations in the TP53 gene are extremely common and occur very early in the progression of serous ovarian cancers. Gene expression patterns that relate to mutational status may provide insight into the etiology and biology of the disease. METHO ...
Full textOpen AccessLink to itemCite
Journal ArticleJ Clin Oncol · May 1, 2010
PURPOSE: Identifying sources of variation in expression microarray data and the effect of variance in gene expression measurements on complex predictive and diagnostic models is essential when translating microarray-based experimental approaches into clini ...
Full textLink to itemCite
Journal ArticleJ Clin Oncol · May 1, 2010
PURPOSE: Early detection of ovarian cancer has great promise to improve clinical outcome. PATIENTS AND METHODS: Ninety-six serum biomarkers were analyzed in sera from healthy women and from patients with ovarian cancer, benign pelvic tumors, and breast, co ...
Full textLink to itemCite
Journal ArticleJ Am Coll Surg · May 2010
BACKGROUND: Axillary lymph node status remains the most important prognostic factor in breast cancer. Established staging systems emphasize the absolute number of positive nodes, without regard for the total number of lymph nodes examined. We sought to con ...
Full textLink to itemCite
Journal ArticlePLoS One · April 8, 2010
BACKGROUND: We analyzed the association between 53 genes related to DNA repair and p53-mediated damage response and serous ovarian cancer risk using case-control data from the North Carolina Ovarian Cancer Study (NCOCS), a population-based, case-control st ...
Full textOpen AccessLink to itemCite
Journal ArticleGynecol Oncol · March 2010
OBJECTIVE: The objective of this study was to examine the clinicopathologic correlates of T-regulatory (T(reg)) cell infiltration in serous ovarian cancers and to define gene signatures associated with high T(reg)s. METHODS: Tumor infiltrating T(reg) and c ...
Full textLink to itemCite
Journal ArticleClin Cancer Res · March 1, 2010
PURPOSE: Overexpression of the breast cancer oncogene HER2 correlates with poor survival. Current HER2-directed therapies confer limited clinical benefits and most patients experience progressive disease. Because refractory tumors remain strongly HER2+, va ...
Full textLink to itemCite
Journal ArticleCancer Epidemiol Biomarkers Prev · February 2010
Aberrant glycosylation is a well-described hallmark of cancer. In a previous ovarian cancer case control study that examined polymorphisms in 26 glycosylation-associated genes, we found strong statistical evidence (P = 0.00017) that women who inherited two ...
Full textLink to itemCite
Journal ArticleBreast Cancer Res Treat · December 2009
Feasibility and reproducibility of microarray biomarkers in clinical settings are doubted because of reliance on fresh frozen tissue. We sought to develop and validate a paradigm of frozen tissue collection from early breast tumors to enable use of microar ...
Full textLink to itemCite
Journal ArticleInt J Cancer · December 1, 2009
The mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes a protein that plays a critical role in tumor suppression, in part by modulating bioavailability of a potent mitogen, insulin-like growth factor-2 (IGF2). We tested the hypot ...
Full textLink to itemCite
Journal ArticleBiomarkers · August 2009
We used doxorubicin-based chemotherapy as a clinical model for oxidative assault. Study recruited 23 breast cancer patients and collected blood samples before (T0), at 1 (T1) and 24 hours (T24) after treatment administration. Measurements included protein ...
Full textLink to itemCite
Journal ArticleJ Natl Med Assoc · July 2009
BACKGROUND: Individual variation in circulating insulinlike growth factor-1 (IGF1) and its major binding protein, insulinlike growth factor binding protein-3 (IGFBP3), have been etiologically linked to several chronic diseases, including some cancers. Fact ...
Full textLink to itemCite
Journal ArticlePLoS One · June 8, 2009
The chemotherapeutic doxorubicin (DOX) induces DNA double-strand break (DSB) damage. In order to identify conserved genes that mediate DOX resistance, we screened the Saccharomyces cerevisiae diploid deletion collection and identified 376 deletion strains ...
Full textLink to itemCite
Journal ArticleBMC Cancer · May 28, 2009
BACKGROUND: Because screening mammography for breast cancer is less effective for premenopausal women, we investigated the feasibility of a diagnostic blood test using serum proteins. METHODS: This study used a set of 98 serum proteins and chose diagnostic ...
Full textLink to itemCite
Journal ArticleClin Cancer Res · April 15, 2009
PURPOSE: Tumor cell growth and migration can be directly regulated by chemokines. In the present study, the association of CCL11 with ovarian cancer has been investigated. EXPERIMENTAL DESIGN AND RESULTS: Circulating levels of CCL11 in sera of patients wit ...
Full textLink to itemCite
Journal ArticleClin Cancer Res · April 1, 2009
PURPOSE: Although few women with advanced serous ovarian cancer are cured, detection of the disease at an early stage is associated with a much higher likelihood of survival. We previously used gene expression array analysis to distinguish subsets of advan ...
Full textLink to itemCite
Journal ArticleCancer Res · March 15, 2009
The p53 protein is critical for multiple cellular functions including cell growth and DNA repair. We assessed whether polymorphisms in the region encoding TP53 were associated with risk of invasive ovarian cancer. The study population includes a total of 5 ...
Full textLink to itemCite
Journal ArticleMol Cancer Res · February 2009
Dysregulation of MAL (myelin and lymphocyte protein) has been implicated in several malignancies including esophageal, ovarian, and cervical cancers. The MAL protein functions in apical transport in polarized epithelial cells; therefore, its disruption may ...
Full textLink to itemCite
Journal ArticleOncogene · January 15, 2009
The cancer stem cell hypothesis posits that malignant growth arises from a rare population of progenitor cells within a tumor that provide it with unlimited regenerative capacity. Such cells also possess increased resistance to chemotherapeutic agents. Res ...
Full textLink to itemCite
Journal ArticleCancer Chemother Pharmacol · January 2009
PURPOSE: Tumor hypoxia reduces the efficacy of radiation and chemotherapy as well as altering gene expression that promotes cell survival and metastasis. The growth factor receptor, Her2/neu, is overexpressed in 25-30% of breast tumors. Tumors that are Her ...
Full textLink to itemCite
Journal ArticleJ Clin Oncol · July 10, 2008
PURPOSE: Breast cancer arising in young women is correlated with inferior survival and higher incidence of negative clinicopathologic features. The biology driving this aggressive disease has yet to be defined. PATIENTS AND METHODS: Clinically annotated, m ...
Full textLink to itemCite
Journal ArticleMol Cancer Ther · June 2008
Tumor cells are known to exhibit highly varied sensitivity to camptothecins (CPT; e.g., irinotecan and topotecan). However, the factors that determine CPT sensitivity/resistance are largely unknown. Recent studies have shown that the ubiquitin-like protein ...
Full textLink to itemCite
Journal ArticleCancer Epidemiol Biomarkers Prev · March 2008
BACKGROUND: The objective of this study was to determine whether cyclin E overexpression defines an etiologically distinct subgroup of ovarian cancer. METHODS: We analyzed data from 538 epithelial ovarian cancer cases and 629 controls enrolled in a populat ...
Full textLink to itemCite
Journal ArticlePLoS One · January 16, 2008
BRCA1 has been implicated in numerous DNA repair pathways that maintain genome integrity, however the function responsible for its tumor suppressor activity in breast cancer remains obscure. To identify the most highly conserved of the many BRCA1 functions ...
Full textOpen AccessLink to itemCite
Journal ArticlePLoS One · January 2, 2008
PURPOSE: To define the biology driving the aggressive nature of breast cancer arising in young women. EXPERIMENTAL DESIGN: Among 784 patients with early stage breast cancer, using prospectively-defined, age-specific cohorts (young or=6 ...
Full textOpen AccessLink to itemCite
Journal ArticleBreast Cancer Res · 2008
INTRODUCTION: Neoadjuvant chemotherapy has become the standard of care for the diverse population of women diagnosed with locally advanced breast cancer. Serum biomarker levels are increasingly being investigated for their ability to predict therapy respon ...
Full textLink to itemCite
Chapter · December 1, 2007
Current mammographic screeningfor breast cancer is less effective for younger women. To complement mammography for premenopausal women, we investigated the feasibility screening test using 98 blood serum proteins. Because the data set was very noisy and co ...
Full textCite
Journal ArticleJ Natl Med Assoc · July 2007
Carrying the cytosine-adenosine (CA)19 repeat polymorphism in insulin-like growth factor-1 (IGF1) is associated with lower serum proteins and decreased prostate cancer risk. Carrying the -202A/C genotype in insulin-like growth factor binding protein-3 (IGF ...
Link to itemCite
Journal ArticleGynecol Oncol · May 2007
OBJECTIVES: MKK4 is a metastasis suppressor that is downregulated in some ovarian cancers. We sought to investigate whether promoter methylation, loss of heterozygosity, or changes in phosphorylation are involved in MKK4 dysregulation during ovarian carcin ...
Full textLink to itemCite
Journal ArticleCancer Res · April 1, 2007
High-risk susceptibility genes explain <40% of the excess risk of familial ovarian cancer. Therefore, other ovarian cancer susceptibility genes are likely to exist. We have used a single nucleotide polymorphism (SNP)-tagging approach to evaluate common var ...
Full textLink to itemCite
Journal ArticleCancer Res · April 1, 2007
Epithelial cells within the normal breast duct seem to be the primary target for neoplastic transformation events that eventually produce breast cancer. Normal epithelial cells are easily isolated and propagated using standard techniques. However, these te ...
Full textLink to itemCite
Journal ArticleCancer Epidemiol Biomarkers Prev · March 2007
INTRODUCTION: Androgens may play a role in the development of ovarian cancers. Two trinucleotide repeat polymorphisms have been described in exon 1 of the androgen receptor (AR) gene that may affect its function. Previous studies of ovarian cancer and AR r ...
Full textLink to itemCite
OtherJ Clin Oncol · February 10, 2007
PURPOSE: The purpose of this study was to develop an integrated genomic-based approach to personalized treatment of patients with advanced-stage ovarian cancer. We have used gene expression profiles to identify patients likely to be resistant to primary pl ...
Full textLink to itemCite
Journal ArticleCancer Epidemiol Biomarkers Prev · February 2007
BACKGROUND: Multiple identical sets of sera from cancer cases and controls would facilitate standardized testing of biomarkers. We describe the creation and use of standard serum sets developed from healthy donors and pooled sera from ovarian, breast, and ...
Full textLink to itemCite
Journal ArticleJ Clin Invest · January 2007
The TGF-beta signaling pathway has a complex role in regulating mammary carcinogenesis. Here we demonstrate that the type III TGF-beta receptor (TbetaRIII, or betaglycan), a ubiquitously expressed TGF-beta coreceptor, regulated breast cancer progression an ...
Full textLink to itemCite
OtherNat Med · November 2006
Using in vitro drug sensitivity data coupled with Affymetrix microarray data, we developed gene expression signatures that predict sensitivity to individual chemotherapeutic drugs. Each signature was validated with response data from an independent set of ...
Full textLink to itemCite
Journal ArticleGynecol Oncol · June 2006
OBJECTIVE: This study examined MASPIN expression in human ovarian cancer, and explored the association between MASPIN and prognosis in patients with advanced stage disease treated with first-line cisplatin, carboplatin and/or paclitaxel. METHODS: Frozen pr ...
Full textLink to itemCite
Journal ArticleBreast Cancer Res Treat · May 2006
INTRODUCTION: Genes that are expressed in a highly tissue- or disease-specific manner provide possible targets for therapeutics, early detection of cancer, and monitoring of disease burden during and after treatment. Further, genes of this type that code f ...
Full textLink to itemCite
Journal ArticleCancer Res · April 15, 2006
To identify genetic changes involved in the progression of breast carcinoma, we did cDNA array comparative genomic hybridization (CGH) on a panel of breast tumors, including 10 ductal carcinoma in situ (DCIS), 18 invasive breast carcinomas, and two lymph n ...
Full textLink to itemCite
Journal ArticleMol Cancer Res · April 2006
Overexpression of the imprinted insulin-like growth factor-II (IGF2) is a prominent characteristic of gynecologic malignancies. The purpose of this study was to determine whether IGF2 loss of imprinting (LOI), aberrant H19 expression, and/or epigenetic der ...
Full textLink to itemCite
Journal ArticleCancer Res · February 15, 2006
Apoptotic signaling defects both promote tumorigenesis and confound chemotherapy. Typically, chemotherapeutics stimulate cytochrome c release to the cytoplasm, thereby activating the apoptosome. Although cancer cells can be refractory to cytochrome c relea ...
Full textLink to itemCite
Journal ArticleClin Cancer Res · February 1, 2006
PURPOSE: Breast cancer is a heterogeneous disease, and markers for disease subtypes and therapy response remain poorly defined. For that reason, we employed a prospective neoadjuvant study in locally advanced breast cancer to identify molecular signatures ...
Full textLink to itemCite
Journal ArticleNature · January 19, 2006
The development of an oncogenic state is a complex process involving the accumulation of multiple independent mutations that lead to deregulation of cell signalling pathways central to the control of cell growth and cell fate. The ability to define cancer ...
Full textLink to itemCite
Journal ArticleNucleic Acids Res · 2006
Cell surface mannose 6-phosphate/insulin-like growth factor II receptors (M6P/IGF2R) bind and target exogenous insulin-like growth factor II (IGF2) to the prelysosomes where it is degraded. Loss of heterozygosity (LOH) for M6P/IGF2R is found in cancers, wi ...
Full textLink to itemCite
Journal ArticleEpidemiology · January 2006
BACKGROUND: Previous epidemiologic research suggests that analgesic use may reduce the risk of ovarian cancer, although results are not consistent. METHODS: In a population-based, case-control study, we analyzed data from 586 ovarian cancer cases and 627 m ...
Full textLink to itemCite
Journal ArticleInt J Gynecol Cancer · 2006
The molecular etiology of epithelial ovarian cancer remains unclear. Using microarray expression analysis, we recently reported that expression of the insulin-like growth factor binding protein-2 (IGFBP-2) gene is elevated in advanced epithelial ovarian ca ...
Full textLink to itemCite
Journal ArticleInt J Gynecol Cancer · 2006
Although the transition from early- to advanced-stage ovarian cancer is a critical determinant of survival, little is known about the molecular underpinnings of ovarian metastasis. We hypothesize that microarray analysis of global gene expression patterns ...
Full textLink to itemCite
Journal ArticleJ Clin Oncol · September 1, 2005
PURPOSE: To evaluate associations between patient survival, pharmacokinetics, and drug metabolism-related genetic polymorphisms in patients receiving a combination chemotherapy regimen for breast cancer. PATIENTS AND METHODS: A genotype association study w ...
Full textLink to itemCite
Journal ArticleClin Cancer Res · May 15, 2005
PURPOSE: A better understanding of the underlying biology of invasive serous ovarian cancer is critical for the development of early detection strategies and new therapeutics. The objective of this study was to define gene expression patterns associated wi ...
Full textLink to itemCite
Journal ArticleGynecol Oncol · May 2005
OBJECTIVES: It has been suggested that the 6A allele of the type I TGFbeta receptor (TGFbetaR1) polyalanine repeat tract polymorphism may increase susceptibility to various types of cancer including ovarian cancer. METHODS: The TGFbetaR1 polyalanine polymo ...
Full textLink to itemCite
Journal ArticleOncogene · April 14, 2005
Treatment of the breast cancer cell line, MDAMB468 with the DNA methylation inhibitor, 5-azacytidine (5-AzaC) results in growth arrest, whereas the growth of the normal breast epithelial line DU99 (telomerase immortalized) is relatively unaffected. Compari ...
Full textLink to itemCite
Journal ArticleGynecol Oncol · February 2005
OBJECTIVE: Epithelial ovarian cancer is the deadliest gynecologic malignancy, yet its molecular etiology remains poorly understood. Evidence is accumulating to support a role for the insulin-like growth factor family in human carcinogenesis, and recently u ...
Full textLink to itemCite
Journal ArticleCancer Epidemiol Biomarkers Prev · February 2005
We investigated the relationship between the insulin-like growth factor-1 (IGF1) cytosine-adenine repeat (CA)(19) polymorphism located upstream of the gene's transcription start site, the insulin-like growth factor binding protein-3 (IGFBP3) -202 A/C promo ...
Full textLink to itemCite
Journal ArticleCancer Epidemiol Biomarkers Prev · December 2004
OBJECTIVE: The progestagenic milieu of pregnancy and oral contraceptive use is protective against epithelial ovarian cancer. A functional single nucleotide polymorphism in the promoter of the progesterone receptor (+331A) alters the relative abundance of t ...
Link to itemCite
Journal ArticleMol Cancer Res · August 2004
TAFII70, a member of the basal transcription complex implicated in p53-mediated transcription, is synthesized as several alternately spliced variants. The predominant forms found in normal and neoplastic breast epithelial cells are shown to be 72 kDa (TAFI ...
Link to itemCite
Journal ArticleClin Cancer Res · July 15, 2004
PURPOSE: Spread to the central nervous system (CNS) and the leptomeninges is a frequent complication of systemic cancers that is associated with serious morbidity and high mortality. We have evaluated a novel therapeutic approach against CNS complications ...
Full textLink to itemCite
Journal ArticleMol Cell Biol · May 2004
The late stages of human breast cancer development are poorly understood complex processes associated with the expression of genes by cancers that promote specific tumorigenic activities, such as angiogenesis. Here, we describe the identification of perios ...
Full textLink to itemCite
Journal ArticleGenes Chromosomes Cancer · May 2004
Alterations in estrogen responsive pathways are thought to contribute to benign and malignant breast disease. It has been reported previously that more than a third of typical epithelial hyperplasia lesions harbor the missense mutation A908G in the estroge ...
Full textLink to itemCite
Journal ArticleEukaryot Cell · April 2004
To identify new nonessential genes that affect genome integrity, we completed a screening for diploid mutant Saccharomyces cerevisiae strains that are sensitive to ionizing radiation (IR) and found 62 new genes that confer resistance. Along with those prev ...
Full textLink to itemCite
Journal ArticleAm J Obstet Gynecol · April 2004
OBJECTIVE: The purpose of this study was to define gene expression patterns that are associated with the optimal versus suboptimal debulking of advanced-stage serous ovarian cancers. STUDY DESIGN: RNA from 44 advanced serous ovarian cancers (19 optimal, 25 ...
Full textLink to itemCite
Journal ArticleJ Soc Gynecol Investig · January 2004
OBJECTIVE: To identify gene expression patterns that characterize advanced stage serous ovarian cancers by using microarray expression analysis. METHODS: Using genome-wide expression analysis, we compared a series of 31 advanced stage (III or IV) serous ov ...
Full textLink to itemCite
Journal ArticleClin Cancer Res · October 1, 2003
PURPOSE: Because inherited BRCA1 or BRCA2 mutations strikingly increase ovarian cancer risk, polymorphisms in these genes could represent low penetrance susceptibility alleles. Previous studies of the BRCA2 N372H polymorphism suggested that HH homozygotes ...
Link to itemCite
Journal ArticleProc Natl Acad Sci U S A · September 16, 2003
Using serial analysis of gene expression (SAGE), we identified a SAGE tag that was present only in invasive breast carcinomas and their lymph node metastases. The transcript corresponding to this SAGE tag, dermcidin (DCD), encodes a secreted protein normal ...
Full textLink to itemCite
Journal ArticleJ Soc Gynecol Investig · September 2003
OBJECTIVE: It has been suggested that the 2G allele of a guanine insertion-deletion promoter polymorphism in the promoter of the matrix metalloproteinase-1 (MMP1) gene may increase susceptibility to ovarian cancer. The 2G allele also has been associated wi ...
Full textLink to itemCite
Journal ArticleJ Steroid Biochem Mol Biol · September 2003
Adjuvant endocrine therapy reduces the risk of relapse and death from early stage hormone receptor positive breast cancer. However, tamoxifen is only partially effective because of the development of tumor resistance. Aromatase inhibitors (letrozole, anast ...
Full textLink to itemCite
Journal ArticleJ Surg Res · July 2003
BACKGROUND: Heterologous expression of the tumor suppressor BRCA1 in the yeast Saccharomyces cerevisiae is lethal. To identify potential new BRCA1-interacting gene targets, we characterized highly conserved ionizing radiation (IR) sensitive gene deletions ...
Full textLink to itemCite
Journal ArticleCancer Cell · March 2003
Representational difference analysis (RDA) of human breast cancer was used to discover a novel amplicon located at chromosomal region 8q24.3. We examined a series of breast cancer samples harboring amplification of this region and determined that KCNK9 is ...
Full textLink to itemCite
Journal ArticleMol Cancer Res · March 2003
Gene expression patterns in ductal carcinoma in situ (DCIS), and in invasive, and metastatic breast tumors were determined using serial analysis of gene expression (SAGE). We used mRNA in situ hybridization to examine gene expression at the cellular level ...
Link to itemCite
Journal ArticleClin Cancer Res · February 2003
PURPOSE: The molecular determinants of survival in ovarian cancer are poorly understood. Using expression microarrays, we recently found that high expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene is associated with pro ...
Link to itemCite
Journal ArticleHybrid Hybridomics · August 2002
The BRCA2 gene has previously been suggested to play a role in proliferation and DNA repair. Germline mutations in the BRCA2 gene predispose individuals to early onset, hereditary breast cancer. To better understand the expression pattern and function of t ...
Full textLink to itemCite
Journal ArticleNat Genet · June 2002
Featured Publication
We found that PPM1D, encoding a serine/threonine protein phosphatase, lies within an epicenter of the region at 17q23 that is amplified in breast cancer. We show that overexpression of this gene confers two oncogenic phenotypes on cells in culture: attenua ...
Full textLink to itemCite
Journal ArticleIn Silico Biol · 2002
We have developed a complete statistical model for the analysis of tumor specific gene expression profiles. The approach provides investigators with a global overview on large scale gene expression data, indicating aspects of the data that relate to tumor ...
Link to itemCite
Journal ArticleGynecol Oncol · December 2001
OBJECTIVE: The aim of this study was to test the hypothesis that p53 mutations are less frequent in ovarian cancers with alterations in other genes that regulate G1 progression. METHODS: Expression of G1 stimulatory (cyclins D1 and E, cdk4, Ki67) and inhib ...
Full textLink to itemCite
Journal ArticleProc Natl Acad Sci U S A · September 25, 2001
Featured Publication
Prognostic and predictive factors are indispensable tools in the treatment of patients with neoplastic disease. For the most part, such factors rely on a few specific cell surface, histological, or gross pathologic features. Gene expression assays have the ...
Full textLink to itemCite
Journal ArticleProc Natl Acad Sci U S A · August 14, 2001
To identify molecular alterations implicated in the initiating steps of breast tumorogenesis, we compared the gene expression profiles of normal and ductal carcinoma in situ (DCIS) mammary epithelial cells by using serial analysis of gene expression (SAGE) ...
Full textLink to itemCite
Journal ArticleCancer Res · August 1, 2001
To identify molecular alterations involved in the initiation and progression of breast carcinomas, we analyzed the global gene expression profiles of normal mammary epithelial cells and in situ, invasive, and metastatic breast carcinomas using serial analy ...
Link to itemCite
Journal ArticleCancer · June 15, 2001
BACKGROUND: A recent report suggested that the number of lymph nodes examined was a strong predictor of survival in patients with lymph node-negative breast carcinoma. Among women who had >or= 20 lymph nodes examined, the risk of dying from breast carcinom ...
Link to itemCite
Journal ArticleOncogene · June 7, 2001
We have identified 14-3-3 sigma (sigma) as a gene whose expression is lost in breast carcinomas, primarily by methylation-mediated silencing. In this report, we investigated the timing of loss of sigma gene expression during breast tumorigenesis in vivo. W ...
Full textLink to itemCite
Journal ArticleCancer Res · March 15, 2001
Cyclin D2 is a member of the D-type cyclins, implicated in cell cycle regulation, differentiation, and malignant transformation. It was noted previously that cyclin D2 is not expressed in the majority of breast cancer cell lines, whereas abundant expressio ...
Link to itemCite
Journal ArticleJ Soc Gynecol Investig · 2001
OBJECTIVE: To determine whether aberrant expression of hormone receptor corepressors or coactivators or defects in estrogen receptor-mediated transcription might underlie resistance of ovarian cancers to hormonal therapy. METHODS: Northern analysis, Wester ...
Link to itemCite
Journal ArticleCancer Res · December 15, 2000
In recent years, significant effort has been made to identify genes that influence breast cancer risk. Because the high-penetrance breast cancer susceptibility genes BRCA1 and 2 play a role only in a small fraction of breast cancer cases, understanding the ...
Link to itemCite
Journal ArticleJ Steroid Biochem Mol Biol · December 1, 2000
Featured Publication
Estrogen mediates the transcription of responsive genes via its interaction with the estrogen receptor (ER). This ligand-dependent transcriptional activity has been the mechanistic basis for understanding estrogen-induced proliferation. However, recent rep ...
Full textLink to itemCite
Journal ArticleNature · June 22, 2000
Expression of the p53 gene protects cells against malignant transformation. Whereas control of p53 degradation has been a subject of intense scrutiny, little is known about the factors that regulate p53 synthesis. Here we show that p53 messenger RNA levels ...
Full textLink to itemCite
Journal ArticleProc Natl Acad Sci U S A · May 23, 2000
Expression of 14-3-3 final sigma (final sigma) is induced in response to DNA damage, and causes cells to arrest in G(2). By SAGE (serial analysis of gene expression) analysis, we identified final sigma as a gene whose expression is 7-fold lower in breast c ...
Full textLink to itemCite
Journal ArticleCell Growth Differ · February 2000
Featured Publication
Estrogen acts to promote DNA synthesis in the MCF-7 human breast cancer cell line via its interaction with high levels of estrogen receptor. The primary mode of estrogen action has been considered to be through transcriptional activation of genes containin ...
Link to itemCite
OtherCME Journal of Gynecologic Oncology · December 1, 1999
It is thought that the cytotoxic effect of chemotherapy drugs is largely due to their ability to initiate programmed cell death (apoptosis). Although the molecular pathways involved in regulation of apoptosis have not been completely elucidated, it has bee ...
Cite
Journal ArticleOncogene · October 28, 1999
Featured Publication
The hereditary breast cancer susceptibility gene, BRCA2, is considered to be a tumor suppressor gene that may be involved in the cellular response to DNA damage. The transcript for this gene is cell cycle regulated with mRNA levels reaching a peak just bef ...
Full textLink to itemCite
Journal ArticleJ Clin Oncol · October 1999
PURPOSE: Recent studies associate telomerase activity with prognostic factors and survival. We compared quantitative telomerase activity in primary tumors with traditional prognostic factors and outcome in a group of invasive but nonmetastatic breast cance ...
Full textLink to itemCite
Journal ArticleBr J Cancer · July 1999
The recently described Bcl10 gene has been suggested to be a major target gene for inactivation in a variety of human cancers. In order to further evaluate the role of this gene in human adult malignancies, we have analysed a series of carcinomas for mutat ...
Full textLink to itemCite
Journal ArticleOncogene · June 3, 1999
The increasing number of breast carcinoma in situ detected by screening procedures makes it imperative to develop improved markers to stratify the risk of invasive cancer. Telomerase is detectable in invasive cancer, but not in normal tissues. We have micr ...
Full textLink to itemCite
Journal ArticleInt J Gynecol Cancer · March 1999
Carcinosarcoma is an aggressive neoplasm of the female genital tract, which comprises 1-2% of malignancies of the uterine corpus. Because of the broad range of differentiation exhibited by these tumors, the precise nature of the relationship between epithe ...
Full textLink to itemCite
Journal ArticleCancer Chemother Pharmacol · 1999
PURPOSE: We have previously reported preferential repair of DNA interstrand crosslinks in the 4-hydroperoxycyclophosphamide-resistant human medulloblastoma cell line D-283 Med (4-HCR). We now report further studies that explored the potential mechanisms un ...
Full textLink to itemCite
Journal ArticleCell Immunol · December 15, 1998
Human breast carcinoma tumor-infiltrating lymphocytes (TIL) express activation antigens in situ indicative of ongoing immune response-CD28, CD45RO, CD69, CD71, and DR. However, interleukin 2 (IL-2) receptor was poorly expressed: CD25 was detected in only 1 ...
Full textLink to itemCite
Journal ArticleClin Cancer Res · October 1998
Featured Publication
Germline mutations in the BRCA1 tumor suppressor gene are thought to be the most common cause of hereditary ovarian cancer. The aim of this study was to explore further the role of BRCA1 alterations in the development of ovarian cancers. We sought to deter ...
Link to itemCite
ConferenceFASEB Journal · March 20, 1998
Tumor infiltrating lymphocytes (TIL) are abundant in primary human carcinomas but display diminished proliferative response to TCR ligation in vitro. We demonstrate by immunocytochemistry analysis that breast carcinoma TII. express both early and late cell ...
Cite
Journal ArticleCancer · March 1, 1998
Featured Publication
BACKGROUND: Screening and surveillance is increasing the detection of early stage breast carcinoma. The ability to predict accurately the response to adjuvant therapy (chemotherapy or tamoxifen therapy) or postlumpectomy radiation therapy in these patients ...
Full textLink to itemCite
Journal ArticleJ Soc Gynecol Investig · 1998
OBJECTIVE: To determine whether large deletions or other alterations in the putative tumor suppressor gene TSG101 play a role in the molecular pathogenesis of breast and ovarian cancers. METHODS: Expression of TSG101 transcripts was examined in breast and ...
Full textLink to itemCite
Journal ArticleAnticancer Res · 1998
The topoisomerase inhibitors, camptothecin and etoposide target the activity of topoisomerase I and II respectively. These agents, or their analogues, are undergoing clinical trials for the treatment of metastatic breast cancer. In this study, we examined ...
Link to itemCite
Journal ArticleBr J Cancer · 1998
Endothelial receptor tyrosine kinases may play important roles in pathological vascular growth, particularly in tumours. In this study, immunohistochemistry was used to evaluate the expression of a novel endothelial receptor tyrosine kinase, Tie2/Tek, in t ...
Full textLink to itemCite
Journal ArticleCancer · February 15, 1997
BACKGROUND: The TNM staging system originated as a response to the need for an accurate, consistent, universal cancer outcome prediction system. Since the TNM staging system was introduced in the 1950s, new prognostic factors have been identified and new m ...
Full textLink to itemCite
Journal ArticleOncogene · January 9, 1997
Featured Publication
Expression of the breast cancer susceptibility gene, BRCA1, is induced by 17-beta estradiol (E2) in estrogen receptor containing breast cancer cell lines. Our previous studies have shown that BRCA1 transcription is also regulated with the cell cycle, reach ...
Full textLink to itemCite
ConferenceFASEB Journal · December 1, 1996
Tissue transglutaminase (tTG) is a calcium-dependent enzyme that catalyzes intermolecular covalent bonds. This protein cross-linking activity of tTG stabilizes the extracellular matrix (ECM) by making it resistant proteolytic degradation. Since angiogenesi ...
Cite
Journal ArticleNucleic Acids Res · November 15, 1996
Antisense activity against erbB-2 of a variety of sulfur-modified oligonucleotides was examined in a breast cancer cell line which overexpresses this oncogene. Using a 15 base anti-erbB-2 sequence previously shown to be effective, various backbone configur ...
Full textLink to itemCite
Journal ArticleLab Invest · November 1996
Tissue transglutaminase (tTG) is postulated to play a role in apoptosis, cell adhesion, metastasis, and extracellular matrix (ECM) assembly. In this study, the distribution and expression of tissue transglutaminase was investigated in normal human mammary ...
Link to itemCite
Journal ArticleMol Carcinog · November 1996
Microsomal epoxide hydrolase (EPHX) is one of many enzymes involved in the metabolism of endogenous and exogenous toxicants. Polymorphic forms of the human EPHX gene have been described that vary in enzymatic activity, and one, Tyr113His, has been associat ...
Full textLink to itemCite
Journal ArticleAm J Obstet Gynecol · November 1996
OBJECTIVES: Mutation and overexpression of the p53 tumor suppressor gene in endometrial cancers are associated with advanced stage and poor survival. We sought to determine whether p53 overexpression is an independent variable predictive of poor prognosis ...
Full textLink to itemCite
Journal ArticleCancer Res · October 15, 1996
Identifying the conditions and kinetics of the induction of BRCA2 gene expression may implicate roles for the function of the tumor suppressor gene. In this study, expression of BRCA2 mRNA is shown to be regulated by the cell cycle and associated with prol ...
Link to itemCite
Journal ArticleOncogene · September 19, 1996
The p53 gene is a recessive oncogene whose loss of function can result in cell transformation. Approximately 25% of human breast cancers contain missense mutations in one p53 allele, leading to inactivation of the mutated protein. In almost all of these ca ...
Link to itemCite
Journal ArticleClin Cancer Res · September 1996
In many cell types, p53-mediated growth inhibition is dependent on induction of p21, which is an inhibitor of cyclin-dependent kinases that are required for cell cycle progression. Failure of mutant p53 proteins to transactivate p21 may lead to uncontrolle ...
Link to itemCite
Journal ArticleCell Growth Differ · June 1996
Featured Publication
Insight into the function of the BRCA1 tumor suppressor gene may be gained by studying its regulation. In this study, the expression of BRCA1 was examined as a function of the cell cycle in normal and tumor-derived breast epithelial cells. Cells arrested i ...
Link to itemCite
Journal ArticleNat Genet · June 1996
The second hereditary breast cancer gene, BRCA2, was recently isolated. Germline mutations of this gene predispose carriers to breast cancer, and, to a lesser extent, ovarian cancer. Loss of heterozygosity (LOH) at the BRCA2 locus has been observed in 30-4 ...
Full textLink to itemCite
Journal ArticleOncogene · May 2, 1996
The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2r) functions in the activation of TGFbeta, a potent growth inhibitor for most cell types, the degradation of the mitogen, IGF2, and the intracellular trafficking of lysosomal enzymes. W ...
Link to itemCite
Journal ArticleJ Biol Chem · September 29, 1995
We have utilized a genetic selection system in yeast to identify novel estrogen-responsive genes within the human genome and to define the sequences in the BRCA-1 gene responsible for its estrogen responsiveness. This approach led to the identification of ...
Full textLink to itemCite
Journal ArticleProc Natl Acad Sci U S A · August 29, 1995
A causal role has been inferred for ERBB2 overexpression in the etiology of breast cancer and other epithelial malignancies. The development of therapeutics that inhibit this tyrosine kinase cell surface receptor remains a high priority. This report descri ...
Full textLink to itemCite
Journal ArticleBreast Cancer Res Treat · June 1995
Ductal carcinoma in situ (intraductal carcinoma) of the breast is a commonly recognized and curable clinical entity. Patients with intraductal carcinoma are at risk to develop invasive breast cancer presumably due to a transition from the noninvasive to th ...
Full textLink to itemCite
Journal ArticleClin Cancer Res · June 1995
Historical information and pathological material from 150 consecutive patients with localized adenocarcinoma of the lung was collected to evaluate oncogene expression of erbB-2 and p53, and erbB-2 gene amplification. Pathological material after resection w ...
Link to itemCite
Journal ArticleArch Pathol Lab Med · January 1995
Although simultaneous endometrial and ovarian tumors are observed occasionally, rarely are the two neoplasms histologically disparate. We report a case of simultaneous endometrial malignant mixed mesodermal tumor and ovarian serous adenocarcinoma with a si ...
Link to itemCite
Journal ArticleCancer Res · January 1, 1995
In order to construct a multivariate model for predicting early recurrence and cancer death for patients with stage I non-small cell lung cancer, 271 consecutive patients (mean age, 63 +/- 8 years) who were diagnosed, treated, and followed at one instituti ...
Link to itemCite
Journal ArticleThe Breast Journal · January 1, 1995
Abstract: Several clinicopathologic variables influence prognosis in breast cancer, including stage, histologic grade, nodal status, and tumor size. Multiple studies have shown an independent value of proliferation index as a prognostic variable for the st ...
Full textCite
Journal ArticleCell Growth Differ · December 1994
Featured Publication
Transforming growth factor beta (TGF beta) is an important regulator of cellular proliferation. In normal ovarian epithelial cells, TGF beta acts to inhibit growth. However, in ovarian cancer cell lines, this effect is usually lost. Although the regulatory ...
Link to itemCite
Journal ArticleScience · October 7, 1994
Loss of heterozygosity data from familial tumors suggest that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian ca ...
Full textLink to itemCite
Journal ArticleGenomics · September 1, 1994
The VH1-related human protein (VHR) gene was localized to human chromosome 17q21 in a region thought to contain the BRCA1 locus, a locus that confers susceptibility to breast and ovarian cancer. VHR encodes a phosphatase with dual specificity for tyrosine ...
Full textLink to itemCite
Journal ArticleHum Mol Genet · August 1994
Using the technique of solution hybridization coupled with magnetic bead capture, we have isolated a novel homeobox-containing gene from the BRCA1 region of 17q21. This gene is the human homologue of the mouse Mox1 gene previously localized to a syntenic r ...
Full textLink to itemCite
Journal ArticleCancer Genet Cytogenet · August 1994
Cytogenetic and molecular analyses of human breast cancer cells have identified consistent losses of specific chromosomal regions in these tumors, suggesting that such regions harbor tumor suppressor genes whose homozygous loss or inactivation directly con ...
Full textLink to itemCite
Journal ArticleCancer Res · April 1, 1994
We have previously described a common region of deletion and allele loss on chromosome 17q in sporadic breast cancers that is likely to contain a tumor suppressor gene. The region, mapped to 17q12-q21, was bordered by D17S250 and D17S579 on the centromeric ...
Link to itemCite
Journal ArticleAnn Surg · April 1994
OBJECTIVE: Overexpression of the p53 and HER-2/neu oncogenes are the two most common genetic abnormalities associated with breast cancer. Shorter survival time has been reported in patients with tumors with p53 or HER-2/neu. This report analyzes a retrospe ...
Full textLink to itemCite
Journal ArticleExp Cell Res · February 1994
The extracellular matrix glycoprotein tenascin is limited to the periductal matrix of normal breast tissue but is markedly increased in both malignant and fibroadenomatous proliferations. It has been hypothesized that the changes in tenascin expression in ...
Full textLink to itemCite
Journal ArticleObstet Gynecol · January 1994
OBJECTIVE: To determine the frequency of mutation and overexpression of the p53 tumor suppressor gene in female genital tract sarcomas. METHODS: Immunostaining for p53 was performed in frozen sections of 46 ovarian and uterine sarcomas. Single-stranded con ...
Link to itemCite
Journal ArticleMod Pathol · November 1993
The c-erbB-2 (HER-2/neu) proto-oncogenes is important in oncogenesis and for determination of prognosis in a number of human malignancies. DNA (Southern) hybridization and immunoblotting (Western) techniques are most commonly utilized for determining ampli ...
Link to itemCite
Journal ArticleJ Natl Cancer Inst · September 15, 1993
BACKGROUND: The p53 gene encodes a nuclear phosphoprotein present in low levels in normal human cells. The wild-type form of this protein functions to restrain inappropriate cellular proliferation. Approximately one half of human epithelial ovarian cancers ...
Full textLink to itemCite
Journal ArticleAm J Obstet Gynecol · September 1993
OBJECTIVE: Mutation and overexpression of the p53 gene occur in approximately 20% of endometrial carcinomas. To determine whether alteration of the p53 gene is an early event in endometrial carcinogenesis, we examined the p53 gene in endometrial hyperplasi ...
Full textLink to itemCite
Journal ArticleExp Cell Res · August 1993
Normal and neoplastic epithelial cells produce growth factors that can affect cells from different lineages. Epithelial ovarian cancers produce M-CSF and IL-6. In the present study, production of these cytokines has been measured in the apparently normal e ...
Full textLink to itemCite
Journal ArticleObstet Gynecol · May 1993
OBJECTIVE: To investigate whether mutation and overexpression of p53 is a feature of early-stage ovarian cancers. METHODS: Because early-stage ovarian cancers are relatively uncommon, we adapted p53 immunostaining and DNA sequencing methods for use in para ...
Link to itemCite
Journal ArticleJ Natl Cancer Inst · December 2, 1992
BACKGROUND: It has been suggested that multiple sites of epithelial ovarian carcinoma on the peritoneal surface reflect polyclonal disease arising from multiple primary tumors in the peritoneal mesothelium, rather than monoclonal disease spread by metastas ...
Full textLink to itemCite
Journal ArticleAm J Obstet Gynecol · December 1992
OBJECTIVE: We examined the effect of interferon gamma on proliferation and epidermal growth factor receptor expression in ovarian cancer cell lines and normal ovarian epithelial cells. STUDY DESIGN: The tritiated thymidine incorporation assay was used to a ...
Full textLink to itemCite
Journal ArticleJ Histochem Cytochem · July 1992
Mutation and overexpression of the p53 gene have been noted in a wide range of human cancers and are thought to play a role in malignant transformation. Previously, immunohistochemical detection of p53 has been possible only in fresh-frozen tissues. We exa ...
Full textLink to itemCite
Journal ArticleCancer Res · May 1, 1992
Analyses of losses of heterozygosity and linkage studies have implicated a gene(s) on chromosome 17q in the genesis of sporadic and early-onset familial breast carcinomas, respectively. To define the critical region of 17q, we examined DNAs from a series o ...
Link to itemCite
Journal ArticleProc Natl Acad Sci U S A · April 15, 1992
Featured Publication
Overexpression of the p53 protein, resulting from gene mutations that increase protein stability, has been detected in greater than 25% of primary human breast cancers. In addition, approximately 10% of breast cancer patients have circulating antibodies to ...
Full textLink to itemCite
Journal ArticleCancer Res · March 15, 1992
Immunohistochemical staining for the p53 protein was performed in 107 snap frozen primary endometrial adenocarcinomas and 15 benign uterine tissues using monoclonal antibody PAb1801. No staining was seen in benign samples, whereas intense nuclear staining ...
Link to itemCite
Journal ArticleOncogene · January 1992
Overexpression of the nuclear phosphoprotein p53 has been detected in many different transformed human cell lines and primary adult tumors. Elevated steady-state levels of p53 appear to be the result of an increase in the stability of the protein and, in a ...
Link to itemCite
Journal ArticleJ Surg Oncol · December 1991
Overexpression of the nuclear phosphoprotein p53 is one of the most frequently detected abnormalities in human cancer and appears to be associated with mutation of the p53 gene. In this study of breast cancer, p53 overexpression was detected in two (15%) o ...
Full textLink to itemCite
Journal ArticleJ Surg Oncol · September 1991
To investigate factors involved in progression of breast cancer, we estimated the growth fraction of malignant cell populations in various stages of mammary cancer growth. Frozen sections were immunostained with the Ki-67 monoclonal antibody and the prolif ...
Full textLink to itemCite
Journal ArticleSurgery · August 1991
The nuclear phosphoprotein p53 is expressed in all normal cells and appears to function in cell cycle regulation. Abnormally high levels of the protein are found in many different types of cancer. In breast carcinoma overexpression of p53 is associated wit ...
Link to itemCite
Journal ArticleProc Natl Acad Sci U S A · June 1, 1991
Overexpression of an activated form of the p53 protein may be involved in neoplastic transformation. We found widespread overexpression of p53 by immunohistochemical staining in 11 (22%) of 49 primary invasive human breast cancers. Northern blot analysis s ...
Full textLink to itemCite
Journal ArticleCancer Res · June 1, 1991
We examined p53 expression in 107 epithelial ovarian cancers with immunohistochemical techniques using monoclonal antibody PAb1801. High level expression of nuclear p53 protein was detected in the malignant epithelium in 54 (50%) of these cancers. Expressi ...
Link to itemCite
Journal ArticleCancer Res · May 15, 1991
Overexpression of the nuclear phosphoprotein p53 is one of the most common abnormalities in primary human cancer and appears to be due to point mutation within a highly conserved region of the p53 gene which then encodes for a mutant, more stable protein. ...
Link to itemCite
Journal ArticleCancer Res · October 15, 1990
In order to examine the role of the erbB-2 oncogene in human breast cancer, gene amplification and expression were examined in multiple stages of tumor progression. Gene amplification ranging from 2-fold to 32-fold was found in 30 (29%) of 130 cases analyz ...
Link to itemCite
Journal ArticleJ Neurosci Res · September 1989
Transgenic mice harboring the SV40 large T antigen gene in a C57B1/6J genetic background (SV11) first express this gene at 1-2 weeks of age, develop papillomas of the choroid plexus by 80-90 days, and die within 125 days after birth. Transgenic mice harbor ...
Full textLink to itemCite
Journal ArticleJ Virol · February 1989
Transgenic mice that contain the simian virus 40 (SV40) enhancer-promoter and large tumor (T) antigen gene develop papillomas of the choroid plexus. The tumors remain well differentiated on histological examination and express normal levels of tissue-speci ...
Full textLink to itemCite
Journal ArticleVirology · January 1988
Following infection with murine cytomegalovirus (MCMV), the termini of the linear double-stranded DNA genome fuse to form circular or concatemeric forms which serve as replicative intermediates. To investigate the mechanisms involved in the generation and ...
Full textLink to itemCite
Chapter · 1988
A line of transgenic mice that carry the SV40 gene for the large Tumor antigen express this protein during the first two weeks of life in brain tissue. By 30-40 days after birth, independently derived multiple foci of abnormal cells appear throughout the c ...
Link to itemCite
Journal ArticleJ Virol · June 1987
A line of transgenic mice containing the simian virus 40 (SV40) large tumor antigen gene under the control of the viral enhancer-promoter expressed this viral protein in the brains of these mice within the first 2 weeks after birth. Multiple foci of anapla ...
Full textLink to itemCite
Journal ArticleJ Virol · October 1984
The genome of murine cytomegalovirus, extracted from extracellular virions, is a linear double-stranded DNA molecule ca. 240 kilobase pairs long. In our initial cloning of subgenomic fragments of the murine cytomegalovirus genome, we obtained a HindIII clo ...
Full textLink to itemCite
Journal ArticleVirology · November 1983
The sites of transcription and abundance of steady-state cytoplasmic viral RNA in murine cytomegalovirus (Smith strain) infected mouse embryo cells were analyzed. Cloned subgenomic DNA fragments were labeled with 32P and hybridized to filters containing po ...
Full textLink to itemCite
Journal ArticleVirology · August 1983
We have cloned EcoRI and HindIII fragments of the Smith strain of murine cytomegalovirus (MCMV) in the plasmid vector pACYC184. These cloned fragments were used to establish a restriction endonuclease map of the genome with respect to the EcoRI and HindIII ...
Full textLink to itemCite