Scholars@Duke
Jason Andrew Somarelli

Jason Andrew Somarelli

Assistant Professor in Medicine
Medicine, Medical Oncology
jason.somarelli@duke.edu
Box 3053, Durham, NC 27710
3044 Gsrbi, LaSalle Street, Durham, NC 27710

Selected Publications

Mutually exclusive teams-like patterns of gene regulation characterize phenotypic heterogeneity along the noradrenergic-mesenchymal axis in neuroblastoma.

Journal Article Cancer Biol Ther · December 31, 2024 Neuroblastoma is the most frequent extracranial pediatric tumor and leads to 15% of all cancer-related deaths in children. Tumor relapse and therapy resistance in neuroblastoma are driven by phenotypic plasticity and heterogeneity between noradrenergic (NO ... Full text Link to item Cite

Cell-cycle phase progression analysis identifies three unique phenotypes in soft tissue sarcoma.

Journal Article BMC Cancer · October 17, 2024 PURPOSE: Loddo et al. (Br J Cancer 100:959-70, 2009) established the prognostic significance of cell cycle markers and "Cell-Cycle Phenotypes" in breast carcinoma. This study aims to 1) identify prognostic cell-cycle markers in sarcoma, and 2) assess the p ... Full text Link to item Cite

Exploring versatile applications of a vacuum-assisted bone harvester in orthopedic surgery.

Journal Article BMC Musculoskelet Disord · August 31, 2024 BACKGROUND: Orthopedic procedures often require removing bone or pathological tissue, with traditional methods involving instruments like curettes and rongeurs. However, these methods can be time-consuming and lead to increased blood loss. To mitigate thes ... Full text Link to item Cite

Increased prevalence of hybrid epithelial/mesenchymal state and enhanced phenotypic heterogeneity in basal breast cancer

Journal Article iScience · July 19, 2024 Intra-tumoral phenotypic heterogeneity promotes tumor relapse and therapeutic resistance and remains an unsolved clinical challenge. Decoding the interconnections among different biological axes of plasticity is crucial to understand the molecular origins ... Full text Cite

The Known and Unknown: Investigating the Carcinogenic Potential of Plastic Additives.

Journal Article Environ Sci Technol · June 18, 2024 Microplastics are routinely ingested and inhaled by humans and other organisms. Despite the frequency of plastic exposure, little is known about its health consequences. Of particular concern are plastic additives─chemical compounds that are intentionally ... Full text Link to item Cite

ATRX and Its Prognostic Significance in Soft Tissue Sarcoma.

Journal Article Sarcoma · 2024 PURPOSE: Recently, the association between ATRX and a more aggressive sarcoma phenotype has been shown. We performed a retrospective study of sarcomas from an individual institution to evaluate ATRX as a prognosticator in soft tissue sarcoma. Experimental ... Full text Link to item Cite

A Species within a Species

Chapter · January 1, 2024 Chapter 1 introduces cancer as a speciation event that is inexorably linked to multicellularity and marked by a return to unicellularity. Although each cancer arises as an independent speciation event, common ecological features drive convergent evolution ... Full text Cite

Multicellularity, Phenotypic Heterogeneity, and Cancer

Chapter · January 1, 2024 Cancer is a result of the breakdown in processes governing multicellularity, leading to a population of cells that no longer abide by the cues of their multicellular context and begin to act as a population of unicellular organisms within the body. This ch ... Full text Cite

What Do We Gain from Viewing Cancer through an Eco-Evo Lens?

Chapter · January 1, 2024 This chapter summarizes the main points of the prior chapters, discusses the benefits of incorporating ecological and evolutionary perspectives into research and treatment of cancer, and highlights gaps in our knowledge. In particular, the chapter discusse ... Full text Cite

Cancer through the Lens of Evolution and Ecology

Book · January 1, 2024 New cancer cells exist in an ever-changing “ecology” and are subject to evolutionary pressures just like any species in nature. This edited book explores the following themes: 1) how the dynamics of mutation, epigenetics, and gene expression noise are sour ... Full text Cite

Dynamical hallmarks of cancer: Phenotypic switching in melanoma and epithelial-mesenchymal plasticity.

Journal Article Semin Cancer Biol · November 2023 Phenotypic plasticity was recently incorporated as a hallmark of cancer. This plasticity can manifest along many interconnected axes, such as stemness and differentiation, drug-sensitive and drug-resistant states, and between epithelial and mesenchymal cel ... Full text Link to item Cite

Dynamical modeling of proliferative-invasive plasticity and IFNγ signaling in melanoma reveals mechanisms of PD-L1 expression heterogeneity.

Journal Article J Immunother Cancer · September 2023 BACKGROUND: Phenotypic heterogeneity of melanoma cells contributes to drug tolerance, increased metastasis, and immune evasion in patients with progressive disease. Diverse mechanisms have been individually reported to shape extensive intra-tumor and inter ... Full text Link to item Cite

Transcriptomic Signatures Associated With Outcomes in Recurrent Prostate Cancer Treated With Salvage Radiation, Androgen-Deprivation Therapy, and Enzalutamide: Correlative Analysis of the STREAM Trial.

Journal Article JCO Precis Oncol · August 2023 PURPOSE: Men with rising prostate-specific antigen (PSA) after radical prostatectomy (RP) may progress despite radiation and androgen-deprivation therapy (ADT). Tissue-based transcriptomic signatures can identify who may benefit from a more aggressive syst ... Full text Link to item Cite

Atrx deletion impairs CGAS/STING signaling and increases sarcoma response to radiation and oncolytic herpesvirus.

Journal Article J Clin Invest · July 3, 2023 ATRX is one of the most frequently altered genes in solid tumors, and mutation is especially frequent in soft tissue sarcomas. However, the role of ATRX in tumor development and response to cancer therapies remains poorly understood. Here, we developed a p ... Full text Link to item Cite

Partial EMT and associated changes in cellular plasticity in oncovirus-positive samples

Journal Article Advances in Cancer Biology - Metastasis · July 1, 2023 Oncoviruses exploit diverse host mechanisms to survive and proliferate. These adaptive strategies overlap with mechanisms employed by malignant cells during their adaptation to dynamic micro-environments and for evasion of immune attack. While the role of ... Full text Cite

Allometric scaling of metabolic rate and cardiorespiratory variables in aquatic and terrestrial mammals.

Journal Article Physiol Rep · June 2023 While basal metabolic rate (BMR) scales proportionally with body mass (Mb ), it remains unclear whether the relationship differs between mammals from aquatic and terrestrial habitats. We hypothesized that differences in BMR allometry would be reflected in ... Full text Link to item Cite

The ELF3 transcription factor is associated with an epithelial phenotype and represses epithelial-mesenchymal transition.

Journal Article J Biol Eng · March 2, 2023 BACKGROUND: Epithelial-mesenchymal plasticity (EMP) involves bidirectional transitions between epithelial, mesenchymal and multiple intermediary hybrid epithelial/mesenchymal phenotypes. While the process of epithelial-mesenchymal transition (EMT) and its ... Full text Link to item Cite

Inequitable distribution of plastic benefits and burdens on economies and public health

Journal Article Frontiers in Marine Science · January 10, 2023 Plastic heterogeneously affects social systems – notably human health and local and global economies. Here we discuss illustrative examples of the benefits and burdens of each stage of the plastic lifecycle (e.g., macroplastic production, consumption, recy ... Full text Cite

Emergent dynamics of underlying regulatory network links EMT and androgen receptor-dependent resistance in prostate cancer.

Journal Article Comput Struct Biotechnol J · 2023 Advanced prostate cancer patients initially respond to hormone therapy, be it in the form of androgen deprivation therapy or second-generation hormone therapies, such as abiraterone acetate or enzalutamide. However, most men with prostate cancer eventually ... Full text Link to item Cite

A synthetic lethal screen for Snail-induced enzalutamide resistance identifies JAK/STAT signaling as a therapeutic vulnerability in prostate cancer.

Journal Article Front Mol Biosci · 2023 Despite substantial improvements in the treatment landscape of prostate cancer, the evolution of hormone therapy-resistant and metastatic prostate cancer remains a major cause of cancer-related death globally. The mainstay of treatment for advanced prostat ... Full text Link to item Cite

Corrigendum: Psymberin, a marine-derived natural product, induces cancer cell growth arrest and protein translation inhibition.

Journal Article Front Med (Lausanne) · 2023 [This corrects the article DOI: 10.3389/fmed.2022.999004.]. ... Full text Link to item Cite

Genetic and molecular adaptations

Chapter · January 1, 2023 Dolphins and other marine mammals possess unique adaptations that allow them to thrive in aquatic environments. While many physiological and anatomical adaptations play a clear role in marine mammal phenotypes, less is known about how genetic and molecular ... Full text Cite

A growing crisis for One Health: Impacts of plastic pollution across layers of biological function

Journal Article Frontiers in Marine Science · November 2, 2022 The global accumulation of plastic waste has reached crisis levels. The diverse and multilayered impacts of plastic on biological health prompts an evaluation of these effects from a One Health perspective, through which the complexity of these processes c ... Full text Cite

A transdisciplinary approach to reducing global plastic pollution

Journal Article Frontiers in Marine Science · October 28, 2022 Full text Cite

Loss of ATRX promotes aggressive features of osteosarcoma with increased NF-κB signaling and integrin binding.

Journal Article JCI Insight · September 8, 2022 Osteosarcoma (OS) is a lethal disease with few known targeted therapies. Here, we show that decreased ATRX expression is associated with more aggressive tumor cell phenotypes, including increased growth, migration, invasion, and metastasis. These phenotypi ... Full text Link to item Cite

Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry.

Conference Prostate Cancer Prostatic Dis · September 2022 BACKGROUND: Prostate cancer is a clinically and molecularly heterogeneous disease, with highest incidence and mortality among men of African ancestry. To date, prostate cancer patient-derived xenograft (PCPDX) models to study this disease have been difficu ... Full text Open Access Link to item Cite

Questions to guide cancer evolution as a framework for furthering progress in cancer research and sustainable patient outcomes.

Journal Article Med Oncol · July 4, 2022 We appear to be faced with 'two truths' in cancer-one of major advances and successes and another one of remaining short-comings and significant challenges. Despite decades of research and substantial progress in treating cancer, most patients with metasta ... Full text Link to item Cite

Post-Austronesian migrational wave of West Polynesians to Micronesia.

Journal Article Gene · May 20, 2022 This study examines Y-chromosome and mtDNA markers in the population of the island of Kiritimati in the context of geographically targeted reference populations from the Pacific. Kiritimati derives its population from the atoll islands of the Gilbert Archi ... Full text Link to item Cite

A phase 2 trial of avelumab in men with aggressive-variant or neuroendocrine prostate cancer.

Journal Article Prostate Cancer Prostatic Dis · April 2022 BACKGROUND: Men with progressive neuroendocrine or aggressive-variant metastatic prostate cancer (NEPC/AVPC) have a poor prognosis and limited treatment options, and immunotherapy has not been tested in such patients. METHODS: We conducted an open label si ... Full text Link to item Cite

Identifying Modifiable and Non-modifiable Risk Factors of Readmission and Short-Term Mortality in Chondrosarcoma: A National Cancer Database Study.

Journal Article Ann Surg Oncol · February 2022 BACKGROUND: Limited data are available to inform the risk of readmission and short-term mortality in musculoskeletal oncology. The goal of this study was to identify factors independently associated with 30-day readmission and 90-day mortality following su ... Full text Link to item Cite

Extent of tumor fibrosis/hyalinization and infarction following neoadjuvant radiation therapy is associated with improved survival in patients with soft-tissue sarcoma.

Journal Article Cancer Med · January 2022 INTRODUCTION: Current standard of care for most intermediate and high-grade soft-tissue sarcomas (STS) includes limb-preserving surgical resection with either neoadjuvant radiation therapy (NRT) or adjuvant radiation therapy. To date, there have been a few ... Full text Link to item Cite

Exome sequencing of hepatocellular carcinoma in lemurs identifies potential cancer drivers: A pilot study.

Journal Article Evol Med Public Health · 2022 BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma occurs frequently in prosimians, but the cause of these liver cancers in this group is unknown. Characterizing the genetic changes associated with hepatocellular carcinoma in prosimians may point to possi ... Full text Link to item Cite

Mapping phenotypic heterogeneity in melanoma onto the epithelial-hybrid-mesenchymal axis.

Journal Article Front Oncol · 2022 Epithelial to mesenchymal transition (EMT) is a well-studied hallmark of epithelial-like cancers that is characterized by loss of epithelial markers and gain of mesenchymal markers. Melanoma, which is derived from melanocytes of the skin, also undergo phen ... Full text Link to item Cite

Psymberin, a marine-derived natural product, induces cancer cell growth arrest and protein translation inhibition.

Journal Article Front Med (Lausanne) · 2022 Colorectal cancer (CRC) is the third most prevalent form of cancer in the United States and results in over 50,000 deaths per year. Treatments for metastatic CRC are limited, and therefore there is an unmet clinical need for more effective therapies. In ou ... Full text Link to item Cite

Identifying Modifiable and Non-modifiable Risk Factors of Readmission and Short-Term Mortality in Osteosarcoma: A National Cancer Database Study.

Journal Article Ann Surg Oncol · November 2021 BACKGROUND: There are limited data to inform risk of readmission and short-term mortality in musculoskeletal oncology. The goal of this study was to identify factors independently associated with 30-day readmission and 90-day mortality following surgical r ... Full text Link to item Cite

The somatic molecular evolution of cancer: Mutation, selection, and epistasis.

Journal Article Prog Biophys Mol Biol · October 2021 Cancer progression has been attributed to somatic changes in single-nucleotide variants, copy-number aberrations, loss of heterozygosity, chromosomal instability, epistatic interactions, and the tumor microenvironment. It is not entirely clear which of the ... Full text Link to item Cite

KLF4 Induces Mesenchymal-Epithelial Transition (MET) by Suppressing Multiple EMT-Inducing Transcription Factors.

Journal Article Cancers · October 2021 Epithelial-Mesenchymal Plasticity (EMP) refers to reversible dynamic processes where cells can transition from epithelial to mesenchymal (EMT) or from mesenchymal to epithelial (MET) phenotypes. Both these processes are modulated by multiple transcription ... Full text Cite

Treatment of Chondroblastoma with Denosumab: A Case Report with a Correlative Analysis of Effect on the RANK Signaling Pathway.

Journal Article JBJS Case Connect · May 17, 2021 CASE: A 15-year-old boy with chondroblastoma of the right hemipelvis presented with significant periacetabular bone destruction. Neoadjuvant denosumab treatment facilitated initial joint preserving surgery. Unfortunately, he experienced 2 local recurrences ... Full text Link to item Cite

The Hallmarks of Cancer as Ecologically Driven Phenotypes.

Journal Article Front Ecol Evol · April 2021 Ecological fitness is the ability of individuals in a population to survive and reproduce. Individuals with increased fitness are better equipped to withstand the selective pressures of their environments. This paradigm pertains to all organismal life as w ... Full text Link to item Cite

Expression of immune checkpoints on circulating tumor cells in men with metastatic prostate cancer.

Journal Article Biomark Res · February 18, 2021 BACKGROUND: A subset of men with metastatic prostate cancer (mPC) responds to immune checkpoint inhibitors, and there is an unmet need to predict those most likely to benefit. We characterized circulating tumor cells (CTCs) for expression of immune checkpo ... Full text Link to item Cite

Manganese Porphyrin and Radiotherapy Improves Local Tumor Response and Overall Survival in Orthotopic Murine Mammary Carcinoma Models.

Journal Article Radiat Res · February 1, 2021 Novel synthetic compounds, known as manganese porphyrins (MnPs), have been designed to shift the redox status of both normal cells and cancer cells. When MnPs are coupled with cancer therapies, such as radiation, they have been shown to sensitize tumor cel ... Full text Link to item Cite

Exploring the Diversity of the Marine Environment for New Anti-cancer Compounds

Journal Article Frontiers in Marine Science · January 21, 2021 Marine ecosystems contain over 80% of the world’s biodiversity, and many of these organisms have evolved unique adaptations enabling survival in diverse and challenging environments. The biodiversity within the world’s oceans is a virtually untapped resour ... Full text Cite

An integrated comparative physiology and molecular approach pinpoints mediators of breath-hold capacity in dolphins

Journal Article · 2021 Ischemic events, such as ischemic heart disease and ischemic stroke, are the number one cause of death globally. Ischemia prevents blood, carrying essential nutrients and oxygen, from reaching tissues and organ systems, leading to cell and tissue death, an ... Full text Cite

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)<sup>1</sup>.

Journal Article Autophagy · January 2021 In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been ... Full text Cite

Analysis of immune subtypes across the epithelial-mesenchymal plasticity spectrum.

Journal Article Comput Struct Biotechnol J · 2021 Epithelial-mesenchymal plasticity plays a critical role in many solid tumor types as a mediator of metastatic dissemination and treatment resistance. In addition, there is also a growing appreciation that the epithelial/mesenchymal status of a tumor plays ... Full text Link to item Cite

A Zebrafish Model of Metastatic Colonization Pinpoints Cellular Mechanisms of Circulating Tumor Cell Extravasation.

Journal Article Frontiers in oncology · January 2021 Metastasis is a multistep process in which cells must detach, migrate/invade local structures, intravasate, circulate, extravasate, and colonize. A full understanding of the complexity of this process has been limited by the lack of ability to study these ... Full text Cite

An integrated comparative physiology and molecular approach pinpoints mediators of breath-hold capacity in dolphins.

Journal Article Evol Med Public Health · 2021 BACKGROUND AND OBJECTIVES: Ischemic events, such as ischemic heart disease and stroke, are the number one cause of death globally. Ischemia prevents blood, carrying essential nutrients and oxygen, from reaching tissues, leading to cell and tissue death, an ... Full text Link to item Cite

A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer.

Journal Article Mol Cancer Ther · December 2020 Colorectal cancer is the third most common cancer in the United States and responsible for over 50,000 deaths each year. Therapeutic options for advanced colorectal cancer are limited, and there remains an unmet clinical need to identify new treatments for ... Full text Link to item Cite

A Comparative Oncology Drug Discovery Pipeline to Identify and Validate New Treatments for Osteosarcoma.

Journal Article Cancers (Basel) · November 11, 2020 BACKGROUND: Osteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new t ... Full text Link to item Cite

Plastic pollution solutions: emerging technologies to prevent and collectmarineplastic pollution.

Journal Article Environ Int · November 2020 As plastic waste accumulates in the ocean at alarming rates, the need for efficient and sustainable remediation solutions is urgent. One solution is the development and mobilization of technologies that either 1)prevent plastics from entering waterways or2 ... Full text Link to item Cite

Limb salvage versus amputation in patients with osteosarcoma of the extremities: an update in the modern era using the National Cancer Database.

Journal Article BMC Cancer · October 14, 2020 BACKGROUND: Historically, amputation was the primary surgical treatment for osteosarcoma of the extremities; however, with advancements in surgical techniques and chemotherapies limb salvage has replaced amputation as the dominant treatment paradigm. This ... Full text Link to item Cite

Preclinical Testing of a Novel Niclosamide Stearate Prodrug Therapeutic (NSPT) Shows Efficacy Against Osteosarcoma.

Journal Article Mol Cancer Ther · July 2020 Therapeutic advances for osteosarcoma have stagnated over the past several decades, leading to an unmet clinical need for patients. The purpose of this study was to develop a novel therapy for osteosarcoma by reformulating and validating niclosamide, an es ... Full text Open Access Link to item Cite

Development of a precision medicine pipeline to identify personalized treatments for colorectal cancer.

Journal Article BMC Cancer · June 24, 2020 BACKGROUND: Metastatic colorectal cancer (CRC) continues to be a major health problem, and current treatments are primarily for disease control and palliation of symptoms. In this study, we developed a precision medicine strategy to discover novel therapeu ... Full text Link to item Cite

Discordant and heterogeneous clinically relevant genomic alterations in circulating tumor cells vs plasma DNA from men with metastatic castration resistant prostate cancer.

Journal Article Genes Chromosomes Cancer · April 2020 Circulating tumor cell (CTC) and cell-free (cf) DNA-based genomic alterations are increasingly being used for clinical decision-making in oncology. However, the concordance and discordance between paired CTC and cfDNA genomic profiles remain largely unknow ... Full text Link to item Cite

Immune dysregulation and osteosarcoma: Staphylococcus aureus downregulates TGF-β and heightens the inflammatory signature in human and canine macrophages suppressed by osteosarcoma.

Journal Article Vet Comp Oncol · March 2020 Since William Coley utilized bacterial immunotherapy to treat sarcomas in the late 19th century, an association between infection and improved survival has been reported for human and canine osteosarcoma patients. One of the reasons for this improved survi ... Full text Link to item Cite

Baby Genomics: Tracing the Evolutionary Changes That Gave Rise to Placentation.

Journal Article Genome Biol Evol · March 1, 2020 It has long been challenging to uncover the molecular mechanisms behind striking morphological innovations such as mammalian pregnancy. We studied the power of a robust comparative orthology pipeline based on gene synteny to address such problems. We infer ... Full text Link to item Cite

Molecular Biology and Evolution of Cancer: From Discovery to Action.

Journal Article Mol Biol Evol · February 1, 2020 Cancer progression is an evolutionary process. During this process, evolving cancer cell populations encounter restrictive ecological niches within the body, such as the primary tumor, circulatory system, and diverse metastatic sites. Efforts to prevent or ... Full text Link to item Cite

Improving Cancer Drug Discovery by Studying Cancer across the Tree of Life.

Journal Article Mol Biol Evol · January 1, 2020 Despite a considerable expenditure of time and resources and significant advances in experimental models of disease, cancer research continues to suffer from extremely low success rates in translating preclinical discoveries into clinical practice. The con ... Full text Link to item Cite

From the Clinic to the Bench and Back Again in One Dog Year: How a Cross-Species Pipeline to Identify New Treatments for Sarcoma Illuminates the Path Forward in Precision Medicine.

Journal Article Front Oncol · 2020 Cancer drug discovery is an inefficient process, with more than 90% of newly-discovered therapies failing to gain regulatory approval. Patient-derived models of cancer offer a promising new approach to identify new treatments; however, for rare cancers, su ... Full text Link to item Cite

Phenotypic plasticity and lineage switching in prostate cancer

Chapter · January 1, 2020 In the United States alone prostate cancer is responsible for nearly 70 days each day. The vast majority of these deaths are due to metastatic spread of therapy-resistant disease. Metastasis and therapy resistance are mediated by phenotypic plasticity in w ... Full text Cite

Molecular determinants for enzalutamide-induced transcription in prostate cancer.

Journal Article Nucleic Acids Res · November 4, 2019 Enzalutamide, a second-generation androgen receptor (AR) antagonist, has demonstrated clinical benefit in men with prostate cancer. However, it only provides a temporary response and modest increase in survival, indicating a rapid evolution of resistance. ... Full text Open Access Link to item Cite

Bioengineering a Future Free of Marine Plastic Waste

Journal Article Frontiers in Marine Science · October 11, 2019 Plastic waste has reached epidemic proportions worldwide, and the production of plastic continues to rise steadily. Plastic represents a diverse array of commonly used synthetic polymers that are extremely useful as durable, economically beneficial alterna ... Full text Cite

E-Cadherin Represses Anchorage-Independent Growth in Sarcomas through Both Signaling and Mechanical Mechanisms.

Journal Article Mol Cancer Res · June 2019 CDH1 (also known as E-cadherin), an epithelial-specific cell-cell adhesion molecule, plays multiple roles in maintaining adherens junctions, regulating migration and invasion, and mediating intracellular signaling. Downregulation of E-cadherin is a hallmar ... Full text Link to item Cite

The Marquesans at the fringes of the Austronesian expansion.

Journal Article Eur J Hum Genet · May 2019 In the present study, 87 unrelated individuals from the Marquesas Archipelago in French Polynesia were typed using mtDNA, Y-chromosome and autosomal (STRs) markers and compared to key target populations from Island South East Asia (ISEA), Taiwan, and West ... Full text Link to item Cite

Prospective Multicenter Validation of Androgen Receptor Splice Variant 7 and Hormone Therapy Resistance in High-Risk Castration-Resistant Prostate Cancer: The PROPHECY Study.

Journal Article J Clin Oncol · May 1, 2019 PURPOSE: Androgen receptor splice variant 7 (AR-V7) results in a truncated receptor, which leads to ligand-independent constitutive activation that is not inhibited by anti-androgen therapies, including abiraterone or enzalutamide. Given that previous repo ... Full text Link to item Cite

Soft Tissue Sarcoma of the Extremities: What Is the Value of Treating at High-volume Centers?

Journal Article Clin Orthop Relat Res · April 2019 BACKGROUND: For many cancer types, survival is improved when patients receive management at treatment centers that encounter high numbers of patients annually. This correlation may be more important with less common malignancies such as sarcoma. Existing e ... Full text Link to item Cite

An Integrative Systems Biology and Experimental Approach Identifies Convergence of Epithelial Plasticity, Metabolism, and Autophagy to Promote Chemoresistance.

Journal Article J Clin Med · February 7, 2019 The evolution of therapeutic resistance is a major cause of death for cancer patients. The development of therapy resistance is shaped by the ecological dynamics within the tumor microenvironment and the selective pressure of the host immune system. These ... Full text Link to item Cite

Hybrid epithelial/mesenchymal phenotypes promote metastasis and therapy resistance across carcinomas.

Journal Article Pharmacol Ther · February 2019 Cancer metastasis and therapy resistance are the major unsolved clinical challenges, and account for nearly all cancer-related deaths. Both metastasis and therapy resistance are fueled by epithelial plasticity, the reversible phenotypic transitions between ... Full text Link to item Cite

Pharmacodynamic study of radium-223 in men with bone metastatic castration resistant prostate cancer.

Journal Article PLoS One · 2019 BACKGROUND: Radium-223 is a targeted alpha-particle therapy that improves survival in men with metastatic castration resistant prostate cancer (mCRPC), particularly in men with elevated serum levels of bone alkaline phosphatase (B-ALP). We hypothesized tha ... Full text Link to item Cite

Survival Outcomes in Cancer Patients Predicted by a Partial EMT Gene Expression Scoring Metric.

Journal Article Cancer Res · November 15, 2017 Metastasis is a significant contributor to morbidity and mortality for many cancer patients and remains a major obstacle for effective treatment. In many tissue types, metastasis is fueled by the epithelial-to-mesenchymal transition (EMT)-a dynamic process ... Full text Link to item Cite

Epithelial/mesenchymal plasticity: how have quantitative mathematical models helped improve our understanding?

Journal Article Mol Oncol · July 2017 Phenotypic plasticity, the ability of cells to reversibly alter their phenotypes in response to signals, presents a significant clinical challenge to treating solid tumors. Tumor cells utilize phenotypic plasticity to evade therapies, metastasize, and colo ... Full text Link to item Cite

EMT and MET: necessary or permissive for metastasis?

Journal Article Mol Oncol · July 2017 Epithelial-to-mesenchymal transition (EMT) and its reverse mesenchymal-to-epithelial transition (MET) have been suggested to play crucial roles in metastatic dissemination of carcinomas. These phenotypic transitions between states are not binary. Instead, ... Full text Link to item Cite

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells.

Journal Article J Vis Exp · April 7, 2017 Phenotypic plasticity refers to a phenomenon in which cells transiently gain traits of another lineage. During carcinoma progression, phenotypic plasticity drives invasion, dissemination and metastasis. Indeed, while most of the studies of phenotypic plast ... Full text Link to item Cite

PhyloOncology: Understanding cancer through phylogenetic analysis.

Journal Article Biochim Biophys Acta Rev Cancer · April 2017 Despite decades of research and an enormity of resultant data, cancer remains a significant public health problem. New tools and fresh perspectives are needed to obtain fundamental insights, to develop better prognostic and predictive tools, and to identif ... Full text Link to item Cite

Whole Genomic Copy Number Alterations in Circulating Tumor Cells from Men with Abiraterone or Enzalutamide-Resistant Metastatic Castration-Resistant Prostate Cancer.

Journal Article Clin Cancer Res · March 1, 2017 Purpose: Beyond enumeration, circulating tumor cells (CTCs) can provide genetic information from metastatic cancer that may facilitate a greater understanding of tumor biology and enable a precision medicine approach.Experimental Design: CTCs and paired le ... Full text Link to item Cite

Mesenchymal-Epithelial Transition in Sarcomas Is Controlled by the Combinatorial Expression of MicroRNA 200s and GRHL2.

Journal Article Mol Cell Biol · October 1, 2016 Phenotypic plasticity involves a process in which cells transiently acquire phenotypic traits of another lineage. Two commonly studied types of phenotypic plasticity are epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET). I ... Full text Open Access Link to item Cite

Distinct routes to metastasis: plasticity-dependent and plasticity-independent pathways.

Journal Article Oncogene · August 18, 2016 The cascade that culminates in macrometastases is thought to be mediated by phenotypic plasticity, including epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT and MET). Although there is substantial support for the role of EMT in driving c ... Full text Open Access Link to item Cite

Snail promotes resistance to enzalutamide through regulation of androgen receptor activity in prostate cancer.

Journal Article Oncotarget · August 2, 2016 Treatment with androgen-targeted therapies can induce upregulation of epithelial plasticity pathways. Epithelial plasticity is known to be important for metastatic dissemination and therapeutic resistance. The goal of this study is to elucidate the functio ... Full text Open Access Link to item Cite

Carcinosarcomas: tumors in transition?

Journal Article Histol Histopathol · June 2015 Carcinosarcomas are rare, biphasic tumors that are comprised of carcinomatous and sarcomatous elements. While the exact mechanism by which these two phenotypes arise within a single tumor remains unclear, molecular evidence indicates that the epitheliod an ... Full text Link to item Cite

Cellular migration and invasion uncoupled: increased migration is not an inexorable consequence of epithelial-to-mesenchymal transition.

Journal Article Mol Cell Biol · September 15, 2014 Metastatic dissemination requires carcinoma cells to detach from the primary tumor and invade through the basement membrane. To acquire these characteristics, epithelial tumor cells undergo epithelial-to-mesenchymal transitions (EMT), whereby cells lose po ... Full text Link to item Cite

The role of epithelial plasticity in prostate cancer dissemination and treatment resistance.

Journal Article Cancer Metastasis Rev · September 2014 Nearly 30,000 men die annually in the USA of prostate cancer, nearly uniformly from metastatic dissemination. Despite recent advances in hormonal, immunologic, bone-targeted, and cytotoxic chemotherapies, treatment resistance and further dissemination are ... Full text Link to item Cite

U1 small nuclear RNA variants differentially form ribonucleoprotein particles in vitro.

Journal Article Gene · April 25, 2014 The U1 small nuclear (sn)RNA participates in splicing of pre-mRNAs by recognizing and binding to 5' splice sites at exon/intron boundaries. U1 snRNAs associate with 5' splice sites in the form of ribonucleoprotein particles (snRNPs) that are comprised of t ... Full text Link to item Cite

Differential immunoglobulin class-mediated responses to components of the U1 small nuclear ribonucleoprotein particle in systemic lupus erythematosus and mixed connective tissue disease.

Journal Article Lupus · November 2013 OBJECTIVE: The objective of this paper is to determine whether patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) possess differential IgM- and IgG-specific reactivity against peptides from the U1 small nuclear ribo ... Full text Link to item Cite

Fluorescence-based alternative splicing reporters for the study of epithelial plasticity in vivo.

Journal Article RNA · January 2013 Alternative splicing generates a vast diversity of protein isoforms from a limited number of protein-coding genes, with many of the isoforms possessing unique, and even contrasting, functions. Fluorescence-based splicing reporters have the potential to fac ... Full text Link to item Cite

Epitope mapping of the U1 small nuclear ribonucleoprotein particle in patients with systemic lupus erythematosus and mixed connective tissue disease.

Journal Article Lupus · March 2011 Systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are autoimmune illnesses characterized by the presence of high titers of autoantibodies directed against a wide range of 'self ' antigens. Proteins of the U1 small nuclear ribonu ... Full text Link to item Cite

Genome-based identification of spliceosomal proteins in the silk moth Bombyx mori.

Journal Article Arch Insect Biochem Physiol · December 2010 Pre-messenger RNA splicing is a highly conserved eukaryotic cellular function that takes place by way of a large, RNA-protein assembly known as the spliceosome. In the mammalian system, nearly 300 proteins associate with uridine-rich small nuclear (sn)RNAs ... Full text Link to item Cite

Alternative splicing in multiple sclerosis and other autoimmune diseases.

Journal Article RNA Biol · 2010 Alternative splicing is a general mechanism for regulating gene expression that affects the RNA products of more than 90% of human genes. Not surprisingly, alternative splicing is observed among gene products of metazoan immune systems, which have evolved ... Full text Open Access Link to item Cite

To what extent did Neanderthals and modern humans interact?

Journal Article Biol Rev Camb Philos Soc · May 2009 Neanderthals represent an extinct hominid lineage that existed in Europe and Asia for nearly 400,000 years. They thrived in these regions for much of this time, but declined in numbers and went extinct around 30,000 years ago. Interestingly, their disappea ... Full text Link to item Cite

U2 snRNA variants are differentially incorporated into spliceosomes

Journal Article Entomological Research · March 1, 2009 In this study, five U2 small nuclear (sn)RNA variants were detected in the posterior silk gland of the Bombyx mori Nistari strain, one of which represents a novel U2 isoform not previously identified in other strains of this species. Following glycerol gra ... Full text Cite

Spliceosomal immunophilins.

Journal Article FEBS Lett · July 9, 2008 The spliceosome is a dynamic, macromolecular complex, which removes non-protein-coding introns from pre-mRNA to form mature mRNA in a process known as splicing. This ribonucleoprotein assembly is comprised of five uridine-rich small nuclear RNAs (snRNAs) a ... Full text Link to item Cite

Structure-based classification of 45 FK506-binding proteins.

Journal Article Proteins · July 2008 The FK506-binding proteins (FKBPs) are a unique group of chaperones found in a wide variety of organisms. They perform a number of cellular functions including protein folding, regulation of cytokines, transport of steroid receptor complexes, nucleic acid ... Full text Link to item Cite

Small nuclear RNA variants of three Bombyx mori strains

Journal Article Entomological Research · March 1, 2008 The spliceosome is a high molecular weight cellular complex responsible for the removal of non-protein coding introns from pre-mRNA to form mature mRNA transcripts. It comprises five major uridine (U)-rich small nuclear (sn)RNAs, to which a number of prote ... Full text Cite

Characterization of immunophilins in the silkmoth Bombyx mori.

Journal Article Arch Insect Biochem Physiol · August 2007 The FK506-binding proteins (FKBPs) perform an extensive variety of functions in numerous organisms from archaea to humans. The FKBPs are distinguished by their peptidyl-prolyl cis-trans isomerase (PPIase) activity and ability to bind the immunosuppressive ... Full text Link to item Cite

Evolution of the 12 kDa FK506-binding protein gene.

Journal Article Biol Cell · June 2007 BACKGROUND INFORMATION: The FKBPs (FK506-binding proteins) belong to a ubiquitous family of proteins that are found in a wide range of taxonomic groups. These proteins participate in a variety of pathways, including protein folding, down-regulation of T-ce ... Full text Link to item Cite

Wildlife identified as major source of Escherichia coli in agriculturally dominated watersheds by BOX A1R-derived genetic fingerprints.

Journal Article J Environ Manage · January 2007 The presence of Escherichia coli in recreational and potable waters is a major concern to the general public as elevated levels of E. coli suggest the presence of pathogenic bacteria and viruses. Unfortunately, traditional microbial techniques do not allow ... Full text Link to item Cite