RESUMO
PURPOSE: To evaluate the diagnostic utility of publicly funded clinical exome sequencing (ES) for patients with suspected rare genetic diseases. METHODS: We prospectively enrolled 297 probands who met eligibility criteria and received ES across 5 sites in Ontario, Canada, and extracted data from medical records and clinician surveys. Using the Fryback and Thornbury Efficacy Framework, we assessed diagnostic accuracy by examining laboratory interpretation of results and assessed diagnostic thinking by examining the clinical interpretation of results and whether clinical-molecular diagnoses would have been achieved via alternative hypothetical molecular tests. RESULTS: Laboratories reported 105 molecular diagnoses and 165 uncertain results in known and novel genes. Of these, clinicians interpreted 102 of 105 (97%) molecular diagnoses and 6 of 165 (4%) uncertain results as clinical-molecular diagnoses. The 108 clinical-molecular diagnoses were in 104 families (35% diagnostic yield). Each eligibility criteria resulted in diagnostic yields of 30% to 40%, and higher yields were achieved when >2 eligibility criteria were met (up to 45%). Hypothetical tests would have identified 61% of clinical-molecular diagnoses. CONCLUSION: We demonstrate robustness in eligibility criteria and high clinical validity of laboratory results from ES testing. The importance of ES was highlighted by the potential 40% of patients that would have gone undiagnosed without this test.
Assuntos
Exoma , Doenças Raras , Humanos , Estudos Prospectivos , Sequenciamento do Exoma , Doenças Raras/diagnóstico , Doenças Raras/genética , Testes Genéticos/métodos , OntárioRESUMO
Silicon carbide nanowires (SiC NWs) exhibit promising features to allow solution-processable electronics to be deployed in harsh environments. By utilizing a nanoscale form of SiC, we were able to disperse the material into liquid solvents, while maintaining the resilience of bulk SiC. This letter reports the fabrication of SiC NW Schottky diodes. Each diode consisted of just one nanowire with an approximate diameter of 160 nm. In addition to analyzing the diode performance, the effects of elevated temperatures and proton irradiation on the current-voltage characteristics of SiC NW Schottky diodes were also examined. The device could maintain similar values for ideality factor, barrier height, and effective Richardson constant upon proton irradiation with a fluence of 1016 ion/cm2 at 873 K. As a result, these metrics have clearly demonstrated the high-temperature tolerance and irradiation resistance of SiC NWs, ultimately indicating that they may provide utility in allowing solution-processable electronics in harsh environments.
RESUMO
We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12-week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first-line DAA therapy; and two after retreatment with second-line DAA). At a median follow-up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4-day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%-20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R - transplants.
Assuntos
Hepatite C Crônica , Hepatite C , Transplante de Rim , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C/prevenção & controle , Hepatite C Crônica/tratamento farmacológico , Humanos , Transplante de Rim/efeitos adversos , TransplantadosRESUMO
The acquisition of cellular invasiveness by breast epithelial cells and subsequent transition from ductal carcinoma in situ (DCIS) to invasive breast cancer is a critical step in breast cancer progression. Little is known about the molecular dynamics governing this transition. We have previously shown that overexpression of the transcriptional regulator TBX3 in DCIS-like cells increases survival, growth, and invasiveness. To explore this mechanism further and assess direct transcriptional targets of TBX3 in a high-resolution, isoform-specific context, we conducted genome-wide chromatin-immunoprecipitation (ChIP) arrays coupled with transcriptomic analysis. We show that TBX3 regulates several epithelial-mesenchymal transition (EMT)-related genes, including SLUG and TWIST1. Importantly, we demonstrate that TBX3 is a direct regulator of SLUG expression, and SLUG expression is required for TBX3-induced migration and invasion. Assessing TBX3 by immunohistochemistry in early-stage (stage 0 and stage I) breast cancers revealed high expression in low-grade lesions. Within a second independent early-stage non-high-grade cohort, we observed an association between TBX3 level in the DCIS and size of the invasive focus. Additionally, there was a positive correlation between TBX3 and SLUG, and TBX3 and TWIST1 in the invasive carcinoma. Pathway analysis revealed altered expression of several proteases and their inhibitors, consistent with the ability to degrade basement membrane in vivo. These findings strongly suggest the involvement of TBX3 in the promotion of invasiveness and progression of early-stage pre-invasive breast cancer to invasive carcinoma through the low-grade molecular pathway. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Transição Epitelial-Mesenquimal , Fatores de Transcrição da Família Snail/metabolismo , Proteínas com Domínio T/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Transdução de Sinais , Fatores de Transcrição da Família Snail/genética , Proteínas com Domínio T/genética , Regulação para CimaRESUMO
Cluster randomised clinical trials present unique challenges in meeting ethical obligations to those who are treated at a randomised site. Obtaining informed consent for research within the context of clinical care is one such challenge. In order to solve this problem it is important that an informed consent process be effective and efficient, and that it does not impede the research or the healthcare. The innovative approach to informed consent employed in the COMPASS study demonstrates the feasibility of upholding ethical standards without imposing undue burden on clinical workflows, staff members or patients who may participate in the research by virtue of their presence in a cluster randomised facility. The COMPASS study included 40 randomised sites and compared the effectiveness of a postacute stroke intervention with standard care. Each site provided either the comprehensive postacute stroke intervention or standard care according to the randomisation assignment. Working together, the study team, institutional review board and members of the community designed an ethically appropriate and operationally reasonable consent process which was carried out successfully at all randomised sites. This achievement is noteworthy because it demonstrates how to effectively conduct appropriate informed consent in cluster randomised trials, and because it provides a model that can easily be adapted for other pragmatic studies. With this innovative approach to informed consent, patients have access to the information they need about research occurring where they are seeking care, and medical researchers can conduct their studies without ethical concerns or unreasonable logistical impediments. TRIAL REGISTRATION NUMBER: NCT02588664, recruiting. This article covers the development of consent process that is currentlty being employed in the study.
Assuntos
Ética em Pesquisa , Consentimento Livre e Esclarecido/ética , Acidente Vascular Cerebral/terapia , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Seleção de Pacientes/ética , Projetos de Pesquisa , RespeitoRESUMO
In this study, we employ molecular dynamics (MD) simulations to probe the spreading of a drop on a superhydrophobic (SH) surface. The SH surface consists of nanopillars and the drop spreads while being in the Cassie-Baxter (CB) state on the nanopillared surface. Most remarkably, unlike the spreading on non-SH surfaces, we witness that the spreading on SH surfaces is not dominated by the motion of the three-phase contact line (TPCL). Rather, the TPCL remains pinned at the edge of a nanopillar and the spreading is ensured by the liquid surface or the liquid-vapor interface (of this pinned TPCL) bending down and wetting the solid adjacent to the TPCL. Such bending may actually enforce a progressive temporal increase in the instantaneous local contact angle eventually making it equal to or more than 180°. This is in sharp contrast to the classical spreading dynamics, where, with the spreading being dictated by the TPCL motion, the local contact angle always decreases with time. We carry out simulations where the solids supporting the nanopillars have vastly different wettabilities; however, this principle of bending-driven spreading is invariably witnessed. In fact, given the recent experimental study on the rolling of drops on SH surfaces manifesting exactly identical liquid-surface-bending-driven drop motion, we can infer that regardless of the drop size (e.g., nanoscopic or millimetric) or the nature of drop motion (spreading or rolling), the motion of drops in the CB state on SH surfaces is universally driven by the bending of liquid surfaces and not by the motion of the TPCL.
RESUMO
Water-graphene wetting interactions are central to several applications such as desalination, water filtration, electricity generation, biochemical sensing, fabrication of fuel cells, and many more. While substantial attention has been devoted to probe the wetting statics of a water drop on graphene, unraveling the possible wetting translucency nature of graphene, very little research has been done on the dynamics of wetting of water drops on graphene-coated solids or free-standing graphene layers. In this paper, we employ molecular dynamics (MD) simulations to study the contact and the spreading of a water nanodrop, quantifying its wetting dynamics, on supported and free-standing graphene. We demonstrate that nanoscale water drops establish contact with graphene by forming patches on graphene, and this patch formation is hastened for graphene layer(s) supported on hydrophilic solids. More importantly, our results demonstrate that the nanodrop spreading dynamics, regardless of the number of graphene layers or the nature of the underlying solid, obey the half-power law, i.e., râ¼t(1/2) (where r is the wetting contact radius and t is the spreading time) for the entire timespan of spreading except towards the very end of the spreading lifetime when the spreading stops. Such a spreading behavior is exactly analogous to the spreading dynamics of nanodroplets for standard solids - this is in sharp contrast to the wetting statics of graphene where the wetting translucency effect makes graphene different from other standard solids.
RESUMO
To produce evidence capable of informing healthcare decision making at all critical levels, pragmatic clinical trials are diverse both in terms of the type of intervention (medical, behavioral, and/or technological) and the target of intervention (patients, clinicians, and/or healthcare system processes). Patients and clinicians may be called on to participate as designers, investigators, intermediaries, or subjects of pragmatic clinical trials. Other members of the healthcare team, as well as the healthcare system itself, also may be affected directly or indirectly before, during, or after study implementation. This diversity in the types and targets of pragmatic clinical trial interventions has brought into focus the need to consider whether existing ethics and regulatory principles, policies, and procedures are appropriate for pragmatic clinical trials. Specifically, further examination is needed to identify how the types and targets of pragmatic clinical trial interventions may influence the assessment of net potential risk, understood as the balance of potential harms and benefits. In this article, we build on scholarship seeking to align ethics and regulatory requirements with potential research risks and propose an approach to the assessment of net risks that is sensitive to the diverse nature of pragmatic clinical trial interventions. We clarify the potential harms, burdens, benefits, and advantages of common types of pragmatic clinical trial interventions and discuss implications for patients, clinicians, and healthcare systems.
Assuntos
Pesquisa Biomédica/ética , Pesquisa Biomédica/normas , Ensaios Clínicos como Assunto/ética , Ensaios Clínicos como Assunto/normas , Segurança do Paciente/normas , Seleção de Pacientes/ética , Projetos de Pesquisa/normas , Humanos , Estados UnidosRESUMO
Improving agricultural production relies on the decisions and actions of farmers and land managers, highlighting the importance of efficient soil monitoring techniques for better resource management and reduced environmental impacts. Despite considerable advancements in soil sensors, their traditional bulky counterparts cause difficulty in widespread adoption and large-scale deployment. Printed electronics emerge as a promising technology, offering flexibility in device design, cost-effectiveness for mass production, and a compact footprint suitable for versatile deployment platforms. This review overviews how printed sensors are used in monitoring soil parameters through electrochemical sensing mechanisms, enabling direct measurement of nutrients, moisture content, pH value, and others. Notably, printed sensors address scalability and cost concerns in fabrication, making them suitable for deployment across large crop fields. Additionally, seamlessly integrating printed sensors with printed antenna units or traditional integrated circuits can facilitate comprehensive functionality for real-time data collection and communication. This real-time information empowers informed decision-making, optimizes resource management, and enhances crop yield. This review aims to provide a comprehensive overview of recent work related to printed electrochemical soil sensors, ultimately providing insight into future research directions that can enable widespread adoption of precision agriculture technologies.
RESUMO
Electrical biosensors, including transistor-based devices (i.e., BioFETs), have the potential to offer versatile biomarker detection in a simple, low-cost, scalable, and point-of-care manner. Semiconducting carbon nanotubes (CNTs) are among the most explored nanomaterial candidates for BioFETs due to their high electrical sensitivity and compatibility with diverse fabrication approaches. However, when operating in solutions at biologically relevant ionic strengths, CNT-based BioFETs suffer from debilitating levels of signal drift and charge screening, which are often unaccounted for or sidestepped (but not addressed) by testing in diluted solutions. In this work, we present an ultrasensitive CNT-based BioFET called the D4-TFT, an immunoassay with an electrical readout, which overcomes charge screening and drift-related limitations of BioFETs. In high ionic strength solution (1X PBS), the D4-TFT repeatedly and stably detects subfemtomolar biomarker concentrations in a point-of-care form factor by increasing the sensing distance in solution (Debye length) and mitigating signal drift effects. Debye length screening and biofouling effects are overcome using a poly(ethylene glycol)-like polymer brush interface (POEGMA) above the device into which antibodies are printed. Simultaneous testing of a control device having no antibodies printed over the CNT channel confirms successful detection of the target biomarker via an on-current shift caused by antibody sandwich formation. Drift in the target signal is mitigated by a combination of: (1) maximizing sensitivity by appropriate passivation alongside the polymer brush coating; (2) using a stable electrical testing configuration; and (3) enforcing a rigorous testing methodology that relies on infrequent DC sweeps rather than static or AC measurements. These improvements are realized in a relatively simple device using printed CNTs and antibodies for a low-cost, versatile platform for the ongoing pursuit of point-of-care BioFETs.
RESUMO
Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.
RESUMO
During the past decade, genetic code expansion has been proved to be a powerful tool for protein studies and engineering. As the key part, a series of orthogonal pairs have been developed to site-specifically incorporate hundreds of noncanonical amino acids (ncAAs) into proteins by using bacteria, yeast, mammalian cells, animals, or plants as hosts. Among them, the pair of tyrosyl-tRNA synthetase/tRNATyr from Methanococcus jannaschii and the pair of pyrrolysyl-tRNA synthetase/tRNAPyl from Methanosarcina species are the most popular ones. Recently, other "not-so-popular" orthogonal pairs have started to attract attentions, because they can provide more choices of ncAA candidates and are necessary for simultaneous incorporation of multiple ncAAs into a single protein. Here, we summarize the development and applications of those "not-so-popular" orthogonal pairs, providing guidance for studying and engineering proteins.
Assuntos
Aminoacil-tRNA Sintetases , RNA de Transferência , RNA de Transferência/genética , RNA de Transferência/metabolismo , Código Genético , Aminoácidos/química , Engenharia de Proteínas , Saccharomyces cerevisiae/metabolismo , Aminoacil-tRNA Sintetases/químicaRESUMO
Nanomaterial-based inks are one of the essential building blocks for printed electronics. Inks consisting of silver nanoparticles have been well received as conductive inks for printed electronics among researchers and industry due to their good electrical performance, relatively low sintering temperature, and wide range of commercial availability. However, homogenous silver nanoparticle inks can lack the appropriate attributes required for robust printed physical sensors. In this work, we demonstrate that fully printed resistive temperature detector (RTD) sensors can benefit from ink hybridization. Specifically, we investigate RTDs printed by aerosol jet printing of hybrid nickel-copper-silver nanoparticle inks. We show that the overall sensitivity of the printed sensors can be enhanced through the introduction of these varied particles due to intentionally incorporated interfacial obstacles within the percolation network. While the temperature coefficient of resistance is decreased, the change in resistance per change in temperature can be maximized through the enhanced scattering provided by nickel and copper particle constituents. We report a sensitivity increase of 300% through utilizing 40% (by volume) mixture of silver and copper/nickel xylene-based inks. The results are corroborated through SEM/EDS analysis to understand the final weight percent of varied elements within the printed thin film. This magnitude of sensitivity opens up the possibility of utilizing printed RTDs for a wider range of sensing applications, where probing electronics are often low-cost.
RESUMO
Advances in imaging have changed prostate radiotherapy through improved biochemical control from focal boost and improved detection of recurrence. These advances are reviewed in the context of prostate stereotactic body radiation therapy (SBRT) and the ARGOS/CLIMBER trial protocol. ARGOS/CLIMBER will evaluate 1) the safety and feasibility of SBRT with focal boost guided by multiparametric MRI (mpMRI) and 18F-PSMA-1007 PET and 2) imaging and laboratory biomarkers for response to SBRT. To date, response to prostate SBRT is most commonly evaluated using the Phoenix Criteria for biochemical failure. The drawbacks of this approach include lack of lesion identification, a high false-positive rate, and delay in identifying treatment failure. Patients in ARGOS/CLIMBER will receive dynamic 18F-PSMA-1007 PET and mpMRI prior to SBRT for treatment planning and at 6 and 24 months after SBRT to assess response. Imaging findings will be correlated with prostate-specific antigen (PSA) and biopsy results, with the goal of early, non-invasive, and accurate identification of treatment failure.
RESUMO
Breast cancer is a heterogeneous disease. Patient outcome varies significantly, depending on prognostic features of patients and their tumors, including patient age, menopausal status, tumor size and histology, nodal status, and so on. Response to treatment also depends on a series of predictive factors, such as hormone receptor and HER2 status. Current treatment guidelines use these features to determine treatment. However, these guidelines are imperfect, and do not always predict response to treatment or survival. Evolving technologies are permitting increasingly large amounts of molecular data to be obtained from tumors, which may enable more personalized treatment decisions to be made. The challenge is to learn what information leads to improved prognostic accuracy and treatment outcome for individual patients.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Metástase Neoplásica , PrognósticoRESUMO
An efficient method is described to radiolabel several dopamine D2 receptor agonists with tritium at high specific activity.
Assuntos
Agonistas de Dopamina/farmacologia , Receptores de Dopamina D2/efeitos dos fármacos , Trítio/química , Agonistas de Dopamina/química , Espectroscopia de Ressonância MagnéticaRESUMO
Availability of trained professionals to assist researchers navigating regulatory pathways for new drug and device development is limited within academic institutions. We created ReGARDD (Regulatory Guidance for Academic Research of Drugs and Devices), a regional forum initially involving regulatory professionals from four Clinical and Translational Science Award (CTSA)-funded institutions, to build and capitalize on local expertise and to develop a regulatory guidance website geared toward academic researchers. Since 2015, members organized 15 forums covering topics such as FDA premarket submissions, gene therapy, and intellectual property for devices and therapeutics. Through user feedback, targeted surveys, and ongoing iterative processes, we refined and maintained a shared regulatory website, which reached 6000+ users in 2019. Website updates improved navigation to drug versus device topic areas, provided new educational content and videos to address commonly asked questions, and created a portal for posting upcoming training opportunities. Survey respondents rated the website favorably and endorsed expanding ReGARDD as a centralized resource. ReGARDD strengthened the regional regulatory workforce, increased regulatory efficiency, and promulgated best organizational and operational practices. Broad-scale deployment of the ReGARDD model across the CTSA consortium may facilitate the creation of a network of regional forums and reduce gaps in access to regulatory support.
RESUMO
Early breast cancer progression involves advancement through specific morphological stages including atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive mammary carcinoma (IMC), although not necessarily always in a linear fashion. Observational studies have examined genetic, epigenetic and gene expression differences in breast tissues representing these stages of progression, but model systems which would allow for experimental testing of specific factors influencing transition through these stages are scarce. The 21T series cell lines, all originally derived from the same patient with metastatic breast cancer, have been proposed to represent a mammary tumor progression series. We report here that three of the 21T cell lines indeed mimic specific stages of human breast cancer progression (21PT-derived cells, ADH; 21NT-derived cells, DCIS; 21MT-1 cells, IMC) when grown in the mammary fat pad of nude mice, albeit after a year. To develop a more rapid, readily manipulatable in vitro assay for examining the biological differences between these cell lines, we have used a 3D Matrigel system. When the three cell lines were grown in 3D Matrigel, they showed characteristic morphologies, in which quantifiable aspects of stage-specific in vivo behaviors (ie, differences in acinar structure formation, cell polarization, colony morphology, cell proliferation, cell invasion) were recapitulated in a reproducible fashion. Gene expression profiling revealed a characteristic pattern for each of the three cell lines. Interestingly, Wnt pathway alterations are particularly predominant in the early transition from 21PTci (ADH) to 21NTci (DCIS), whereas alterations in expression of genes associated with control of cell motility and invasion phenomena are more prominent in the later transition of 21NTci (DCIS) to 21MT-1 (IMC). This system thus reveals potential therapeutic targets and will provide a means of testing the influences of identified genes on transitions between these stages of pre-malignant to malignant growth.
Assuntos
Neoplasias da Mama , Mama/metabolismo , Carcinoma in Situ/patologia , Carcinoma Ductal/patologia , Carcinoma/patologia , Animais , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma in Situ/genética , Carcinoma in Situ/metabolismo , Carcinoma Ductal/genética , Carcinoma Ductal/metabolismo , Colágeno , Progressão da Doença , Combinação de Medicamentos , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Laminina , Camundongos , Camundongos Nus , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Processos Neoplásicos , ProteoglicanasRESUMO
Although lymphatic dissemination is a major route for breast cancer metastasis, there has been little work to determine what factors control the ability of tumor cells to survive, establish and show progressive growth in a lymph node environment. This information is of particular relevance now, in the era of sentinel lymph node biopsy, where smaller intranodal tumor deposits are being detected earlier in the course of disease, the clinical relevance of which is uncertain. In this study, we compared differentially expressed genes in cell lines of high (468LN) vs. low (468GFP) lymphatic metastatic ability, and related these to clinical literature on genes associated with lymphatic metastatic ability and prognosis, to identify genes of potential clinical relevance. This approach revealed differential expression of a set of genes associated with 'cancer stem cell-like' properties, as well as networks of genes potentially associated with survival and autonomous growth. We explored these differences functionally and found that 468LN cells have a higher proportion of cells with a cancer stem cell-like (CD44+/CD24-) phenotype, have a higher clonogenic potential and a greater ability to survive, establish and grow in a foreign (lymph node and 3D Matrigel) microenvironment, relative to 468GFP cells. Differentially expressed genes which reflect these functions provide candidates for investigation as potential targets for therapy directed against early lymphatic metastasis.