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Traumatic, inherited, and age-related degenerative diseases of the retina, such as retinal detachment, retinitis pigmentosa, and age-related macular degeneration, are characterized by the irreversible loss of retinal neurons. While current treatments aim to prevent neuronal degeneration, there are no available treatments to restore neurons after loss. Cultured murine neuroretinal tissue explants model retinal injury and offer a high throughput approach to identify experimental interventions capable of regenerating neurons. Formalin-fixed paraffin-embedded (FFPE) preparations of murine neuroretinal explants can be used to identify cells throughout the retinal layers to provide information on proliferation and activity following exposure to therapeutics. However, retinal explants are friable, particularly after

The natural history and optimal treatment of pleomorphic (PLCIS) and florid (FLCIS) lobular carcinoma in situ variants remains uncertain. We reviewed the clinicopathologic features and management of LCIS variants at our institution over a 20-year period. Of 85 cases (61 PLCIS, 24 FLCIS), 77% were associated with invasive carcinoma (84% lobular, 13% ductal/lobular, 3% ductal) and only 17% (9 PLCIS, 5 FLCIS) were pure. Most (81%) invasive carcinomas were grade 2, with all grade 3/pleomorphic invasive lobular carcinomas (ILC) associated with PLCIS, and all grade 1 tumors associated with FLCIS. PLCIS-associated invasive carcinomas were more often ER- (21%) or HER2+ (14%) than FLCIS-associated tumors (100% ER+, 6% HER2+). LCIS variants were unifocal and co-localized with invasive carcinoma in 20/20 selected spatially mapped cases, whereas classic LCIS (CLCIS) was multifocal with wider distribution (10/17). Of 21 pure LCIS variants on core biopsy, all represented the radiographic (95%) or palpable (5%) target. The excisional upgrade rate was similar for PLCIS (38%) and FLCIS (33%). Pure LCIS variants on core biopsy were often (20%) HER2+ and had a higher Ki-67-index than synchronous CLCIS (P=0.002). Lower ER expression in LCIS variants versus CLCIS was due to ER- apocrine PLCIS. ER and HER2 were consistently concordant between LCIS variants and upgraded ILC but discordant between synchronous CLCIS and LCIS variants in 5/14 (36%). Pure LCIS variants were excised to negative margins and frequently (58%) treated with endocrine but not radiation therapy without recurrences. In summary, PLCIS and FLCIS demonstrate features of direct precursor lesions warranting surgical excision.

Colorectal neuroendocrine carcinomas, both small cell and large cell types, are highly aggressive tumors with poor prognosis compared with colorectal adenocarcinoma. The molecular drivers of neuroendocrine carcinoma are best defined in small cell lung cancer, which shows near-universal genomic alterations in TP53 and RB1. The genetics of colorectal neuroendocrine carcinoma remain poorly understood; recent studies demonstrated infrequent RB1 alterations and genetics closely resembling colorectal adenocarcinoma. To better define the molecular pathogenesis of colorectal neuroendocrine carcinoma, we performed capture-based next-generation sequencing on 25 cases and evaluated for expression of p53, Rb, p16, and high-risk human papillomavirus (HR-HPV) subtypes using immunohistochemistry, in situ hybridization, and polymerase chain reaction. Rb/E2F pathway dysregulation was identified in nearly all cases (23/25, 92%) and occurred via three distinct mechanisms. First, RB1 genomic alteration was present in 56% (14/25) of cases and was accompanied by Rb protein loss, high p16 expression, and absence of HR-HPV; these cases also had frequent genomic alterations in TP53, the PI3K/Ras and Wnt pathways, as well as in DNA repair genes, with 4/14 cases being hypermutated. Second, 16% (4/25) of cases, all left-sided, had TP53 alteration without RB1 alteration; half of these harbored high-level amplifications in CCNE1 and MYC or MYCN and arose in patients with ulcerative colitis. Finally, 28% (7/25) of cases, all rectal or anal, lacked genomic alterations in RB1 or TP53 but were positive for HR-HPV. Our data demonstrate that Rb/E2F pathway dysregulation is essential in the pathogenesis of colorectal neuroendocrine carcinoma, akin to neuroendocrine carcinomas in other anatomic sites. Moreover, colorectal neuroendocrine carcinomas stratify into three distinct molecular subgroups, which can be differentiated based on Rb protein and HR-HPV status. HR-HPV infection represents a distinct mechanism for Rb and p53 inactivation in cases lacking genomic alterations in either gene. Differential treatment strategies for hypermutated and HPV-driven cases could improve patient outcomes.

Goodwin and Nelson discuss the recent discovery by Sirka et al. that remodeling activity of myoepithelial cells can control breast cancer cell invasion., Smooth muscle–like cells can actively remodel epithelia, a mechanism common across developing tissues. In this issue, new work from Sirka et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201802144) demonstrates a novel mechanism for tumor suppression by smooth muscle–like myoepithelial cells of the mammary gland.

Pleomorphic (PLCIS) and florid (FLCIS) lobular carcinoma in situ are rare histologic variants of LCIS that are considered more aggressive than classic LCIS (CLCIS), but optimal treatment is controversial. The genetic drivers of these lesions and their clonal relationships to paired CLCIS and ILC have not been characterized. We used capture-based next-generation sequencing to profile 16 LCIS variants (ten PLCIS, six FLCIS), including paired synchronous ILC and CLCIS in 11 and nine cases, respectively. Recurrent pathogenic alterations included CDH1 (9/10 PLCIS, 6/6 FLCIS), PIK3CA (7/10 PLCIS, 2/6 FLCIS), ERBB2 (6/10 PLCIS, 2/6 FLCIS; six mutations, two amplifications), ERBB3 (1/10 PLCIS, 2/6 FLCIS), FOXA1 (4/10 PLCIS, 1/6 FLCIS), TP53 (3/10 PLCIS), and CCND1 (2/10 PLCIS, 1/6 FLCIS). Mutational profiles and mean copy number alterations (CNA) were similar between LCIS variants with and without ILC. Compared with ILC in The Cancer Genome Atlas (TCGA), PLCIS, FLCIS, and associated ILC were enriched for ERBB2 mutations, and PLCIS was enriched for TP53 and FOXA1 mutations. Shared pathogenic mutations and CNA were identified between the LCIS variant and ILC in all cases, and between CLCIS and the LCIS variant/ILC in 89%. CLCIS to PLCIS progression was associated with increased mean nonsynonymous mutations and additional pathogenic alterations and/or CNA in 80%. Mean nonsynonymous mutations and CNA were similar between PLCIS and ILC, although additional pathogenic mutations were associated with invasion in a subset (43%). FLCIS harbored additional clonal pathogenic mutations in only 1/3 cases, and these were not shared with ILC, which was genetically divergent. In another case, ILC was genetically more similar to CLCIS than FLCIS. The results highlight clonal relationships between PLCIS/FLCIS and CLCIS, and implicate PLCIS as a genetically advanced ILC precursor. Frequent ERBB2/ERBB3 alterations in PLCIS and FLCIS are consistent with more aggressive behavior and may have prognostic and therapeutic implications.

Dissemination is the process by which cells detach and migrate away from a multicellular tissue. The epithelial-to-mesenchymal transition (EMT) conceptualizes dissemination in a stepwise fashion, with downregulation of E-cadherin leading to loss of intercellular junctions, induction of motility, and then escape from the epithelium. This gain of migratory activity is proposed to be mutually exclusive with proliferation. We previously developed a dissemination assay based on inducible expression of the transcription factor Twist1 and here utilize it to characterize the timing and dynamics of intercellular adhesion, proliferation and migration during dissemination. Surprisingly, Twist1+ epithelium displayed extensive intercellular junctions, and Twist1– luminal epithelial cells could still adhere to disseminating Twist1+ cells. Although proteolysis and proliferation were both observed throughout dissemination, neither was absolutely required. Finally, Twist1+ cells exhibited a hybrid migration mode; their morphology and nuclear deformation were characteristic of amoeboid cells, whereas their dynamic protrusive activity, pericellular proteolysis and migration speeds were more typical of mesenchymal cells. Our data reveal that epithelial cells can disseminate while retaining competence to adhere and proliferate., Summary: Twist1+ epithelium retains intercellular junctions and proliferative capacity. During dissemination, Twist1+ cells retain adhesive capacity and exhibit features of both amoeboid and mesenchymal migration modes.

Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is a recently described form of systemic amyloidosis, which most commonly affects the kidney and liver. The LECT2 protein is produced during inflammatory processes, but its precise function in renal diseases in unclear. ALECT2, however, is known to be a relatively common form of renal amyloidosis, after amyloid light chain and serum amyloid A types and is most often seen in patients of Hispanic ethnicity. ALECT2 can occur de novo or as recurrent disease in kidney transplants. We present the first case, to our knowledge, of de novo ALECT2 in a pediatric kidney transplant patient, 15 years post-transplant.

Prelude The previous chapter introduced three of the major subjects of interest in bio-molecular engineering: drug delivery, nano-biotechnology, and tissue engineering. This chapter focuses on additional applications of biomolecular engineering, particularly approaches for enhancing the function of the immune system . The most familiar application of biomedical engineering (BME) in immunology is the development of vaccines . The development of vaccines that are both safe and effective has been one of the great achievements of modern medicine. Because of an effective vaccine, smallpox—a frequently fatal disease that claimed thousands of lives in previous centuries—has been eradicated , or eliminated as a natural infectious agent. Other severe infectious diseases, such as polio and influenza, are now in control in most countries of the world. There are, however, many diseases that have proven to be difficult for vaccine makers. Acquired immune deficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV), has killed millions of people worldwide and there is still no effective vaccine available. In some parts of the world, deaths from HIV/AIDS have a substantial impact on overall life expectancy (Figure 14.1). Most residents of developed nations, such as the United States, receive a spectrum of vaccines during child hood, but there are no vaccines for other diseases (such as malaria, schistosomia sis, and diarrheal disease) that are major causes of death in the developing world (Table 14.1). According to the World Health Organization (WHO), vaccines and clean water are the two public health interventions that have had the most substantial impact on world health. Both of these interventions represent the work of engineers: civil and environmental engineers, who developed water sanitation systems, and bio-medical and chemical engineers, who developed methods for the mass production of safe vaccines. Vaccines prolong the lives of millions of people each year by preventing infectious diseases. Because of the development of an effective and portable vaccine, smallpox—a disease that took the lives of millions and likely caused the fall of Aztec civilizations—has been eradicated from the world.

Colorectal neuroendocrine carcinomas, both small cell and large cell types, are highly aggressive tumors with poor prognosis compared with colorectal adenocarcinoma. The molecular drivers of neuroendocrine carcinoma are best defined in small cell lung cancer, which shows near-universal genomic alterations in TP53 and RB1. The genetics of colorectal neuroendocrine carcinoma remain poorly understood; recent studies demonstrated infrequent RB1 alterations and genetics closely resembling colorectal adenocarcinoma. To better define the molecular pathogenesis of colorectal neuroendocrine carcinoma, we performed capture-based next-generation sequencing on 25 cases and evaluated for expression of p53, Rb, p16, and high-risk human papillomavirus (HR-HPV) subtypes using immunohistochemistry, in situ hybridization, and polymerase chain reaction. Rb/E2F pathway dysregulation was identified in nearly all cases (23/25, 92%) and occurred via three distinct mechanisms. First, RB1 genomic alteration was present in 56% (14/25) of cases and was accompanied by Rb protein loss, high p16 expression, and absence of HR-HPV; these cases also had frequent genomic alterations in TP53, the PI3K/Ras and Wnt pathways, as well as in DNA repair genes, with 4/14 cases being hypermutated. Second, 16% (4/25) of cases, all left-sided, had TP53 alteration without RB1 alteration; half of these harbored high-level amplifications in CCNE1 and MYC or MYCN and arose in patients with ulcerative colitis. Finally, 28% (7/25) of cases, all rectal or anal, lacked genomic alterations in RB1 or TP53 but were positive for HR-HPV. Our data demonstrate that Rb/E2F pathway dysregulation is essential in the pathogenesis of colorectal neuroendocrine carcinoma, akin to neuroendocrine carcinomas in other anatomic sites. Moreover, colorectal neuroendocrine carcinomas stratify into three distinct molecular subgroups, which can be differentiated based on Rb protein and HR-HPV status. HR-HPV infection represents a distinct mechanism for Rb and p53 inactivation in cases lacking genomic alterations in either gene. Differential treatment strategies for hypermutated and HPV-driven cases could improve patient outcomes.

Expression of the transcription factor Twist1 induces dissemination of normal mammary epithelial cells without changing the RNA levels of epithelial-specific genes such as E-cadherin., Dissemination of epithelial cells is a critical step in metastatic spread. Molecular models of dissemination focus on loss of E-cadherin or repression of cell adhesion through an epithelial to mesenchymal transition (EMT). We sought to define the minimum molecular events necessary to induce dissemination of cells out of primary murine mammary epithelium. Deletion of E-cadherin disrupted epithelial architecture and morphogenesis but only rarely resulted in dissemination. In contrast, expression of the EMT transcription factor Twist1 induced rapid dissemination of cytokeratin-positive epithelial cells. Twist1 induced dramatic transcriptional changes in extracellular compartment and cell–matrix adhesion genes but not in cell–cell adhesion genes. Surprisingly, we observed disseminating cells with membrane-localized E-cadherin and β-catenin, and E-cadherin knockdown strongly inhibited Twist1-induced single cell dissemination. Dissemination can therefore occur with retention of epithelial cell identity. The spread of cancer cells during metastasis could similarly involve activation of an epithelial motility program without requiring a transition from epithelial to mesenchymal character.

Fatty-acylation of proteins in eukaryotes is associated with many fundamental cellular processes but has been challenging to study due to limited tools for rapid and robust detection of protein fatty-acylation in cells. The development of azido-fatty acids enabled the nonradioactive detection of fatty-acylated proteins in mammalian cells using the Staudinger ligation and biotinylated phosphine reagents. However, the visualization of protein fatty-acylation with streptavidin blotting is highly variable and not ideal for robust detection of fatty-acylated proteins. Here we report the development of alkynyl-fatty acid chemical reporters and improved bioorthogonal labeling conditions using the Cu(I)-catalyzed Huisgen [3 + 2] cycloaddition that enables specific and sensitive fluorescence detection of fatty-acylated proteins in mammalian cells. These improvements allow the rapid and robust biochemical analysis of fatty-acylated proteins expressed at endogenous levels in mammalian cells by in-gel fluorescence scanning. In addition, alkynyl-fatty acid chemical reporters enable the visualization of fatty-acylated proteins in cells by fluorescence microscopy and flow cytometry. The ability to rapidly visualize protein fatty-acylation in cells using fluorescence detection methods therefore provides new opportunities to interrogate the functions and regulatory mechanisms of fatty-acylated proteins in physiology and disease.

Collective cell responses to exogenous cues depend on cell-cell interactions. In principle, these can result in enhanced sensitivity to weak and noisy stimuli. However, this has not yet been shown experimentally, and, little is known about how multicellular signal processing modulates single cell sensitivity to extracellular signaling inputs, including those guiding complex changes in the tissue form and function. Here we explored if cell-cell communication can enhance the ability of cell ensembles to sense and respond to weak gradients of chemotactic cues. Using a combination of experiments with mammary epithelial cells and mathematical modeling, we find that multicellular sensing enables detection of and response to shallow Epidermal Growth Factor (EGF) gradients that are undetectable by single cells. However, the advantage of this type of gradient sensing is limited by the noisiness of the signaling relay, necessary to integrate spatially distributed ligand concentration information. We calculate the fundamental sensory limits imposed by this communication noise and combine them with the experimental data to estimate the effective size of multicellular sensory groups involved in gradient sensing. Functional experiments strongly implicated intercellular communication through gap junctions and calcium release from intracellular stores as mediators of collective gradient sensing. The resulting integrative analysis provides a framework for understanding the advantages and limitations of sensory information processing by relays of chemically coupled cells., paper + supporting information, total 35 pages, 15 figures

Epithelial tissues are essential for barrier function, secretion, and regulation of fluid transport. Their function requires cell polarity and cell-cell adhesion, mediated through intercellular junctions. Conversely, disruption of adhesion and polarity is thought to drive cancer progression. The mammary gland is an important model for cell adhesion due to its postnatal hormonally regulated development; ducts undergo branching morphogenesis in response to steroid hormones during puberty. These hormonal signals induce a transition from simple to stratified architecture, initiated by asymmetric luminal cell divisions. Ductal elongation is accomplished by this multilayered, low-polarity epithelium, and polarity is reestablished as elongation ceases. The requirement for cell adhesion has been tested in 3D culture and in vivo, using gene deletion, knockdown, and misexpression in both developmental and homeostatic contexts. Attention has focused on E-cadherin, the major classical cadherin in luminal epithelial cells. Classic studies revealed a requirement for E-cadherin during lactation, and E-cadherin loss is widely posited to promote metastasis. However, recent findings demonstrated a broader requirement for E-cadherin during branching morphogenesis and homeostasis and also, surprisingly, in epithelial dissemination. These studies suggest that long-standing models of the role of adhesion in epithelial biology need to be revisited. Advances in inducible gene expression and knockdown, CRISPR/Cas9 technology, and fluorescent labeling of genetically modified cells offer the opportunity to test the roles of diverse adhesion systems and to develop a mechanistic understanding of how cell adhesion regulates development and cancer.

Epithelia are fundamental tissues that line cavities, glands, and outer body surfaces. We use three-dimensional (3D) embedded culture of primary murine mammary epithelial ducts, called "organoids," to recapitulate in days in culture epithelial programs that occur over weeks deep within the body. Modulating the composition of the extracellular matrix (ECM) allows us to model cell- and tissue-level behaviors observed in normal development, such as branching morphogenesis, and in cancer, such as invasion and dissemination. Here, we describe a collection of protocols for 3D culture of mammary organoids in different ECMs and for immunofluorescence staining of 3D culture samples and mammary gland tissue sections. We illustrate expected phenotypic outcomes of each assay and provide troubleshooting tips for commonly encountered technical problems.

Mammalian organs are challenging to study as they are fairly inaccessible to experimental manipulation and optical observation. Recent advances in three-dimensional (3D) culture techniques, coupled with the ability to independently manipulate genetic and microenvironmental factors, have enabled the real-time study of mammalian tissues. These systems have been used to visualize the cellular basis of epithelial morphogenesis, to test the roles of specific genes in regulating cell behaviours within epithelial tissues and to elucidate the contribution of microenvironmental factors to normal and disease processes. Collectively, these novel models can be used to answer fundamental biological questions and generate replacement human tissues, and they enable testing of novel therapeutic approaches, often using patient-derived cells.

Cancer metastasis begins with dissemination of cells from an epithelial tumor. Each tumor contains many mutations and a heterogeneous cell population. As such, it has been difficult to isolate the ...

Breast cancer progression involves genetic changes and changes in the extracellular matrix (ECM). To test the importance of the ECM in tumor cell dissemination, we cultured epithelium from primary human breast carcinomas in different ECM gels. We used basement membrane gels to model the normal microenvironment and collagen I to model the stromal ECM. In basement membrane gels, malignant epithelium either was indolent or grew collectively, without protrusions. In collagen I, epithelium from the same tumor invaded with protrusions and disseminated cells. Importantly, collagen I induced a similar initial response of protrusions and dissemination in both normal and malignant mammary epithelium. However, dissemination of normal cells into collagen I was transient and ceased as laminin 111 localized to the basal surface, whereas dissemination of carcinoma cells was sustained throughout culture, and laminin 111 was not detected. Despite the large impact of ECM on migration strategy, transcriptome analysis of our 3D cultures revealed few ECM-dependent changes in RNA expression. However, we observed many differences between normal and malignant epithelium, including reduced expression of cell-adhesion genes in tumors. Therefore, we tested whether deletion of an adhesion gene could induce sustained dissemination of nontransformed cells into collagen I. We found that deletion of P-cadherin was sufficient for sustained dissemination, but exclusively into collagen I. Our data reveal that metastatic tumors preferentially disseminate in specific ECM microenvironments. Furthermore, these data suggest that breaks in the basement membrane could induce invasion and dissemination via the resulting direct contact between cancer cells and collagen I.

Enteroaggregative Escherichia coli (EAEC) strains have emerged as common causes of persistent diarrhea and malnutrition among children and HIV-infected persons. During infection, EAEC typically adheres to the intestinal mucosa via fimbrial adhesins, which results in a characteristic aggregative pattern. In the study described here we investigated whether the broad-spectrum antiparasitic and antidiarrheal drug nitazoxanide (NTZ) might be active against EAEC in vitro . While E. coli strains were resistant to NTZ in rich Luria-Bertani medium (MIC > 64 μg/ml), the drug was slightly inhibitory in a minimal medium supplemented with glucose (MinA-G medium; MIC, ∼32 μg/ml). NTZ also inhibited biofilm production by strain EAEC 042 in both Dulbecco's modified Eagle's medium and MinA-G medium with a 50% inhibitory concentration of ∼12 μg/ml. Immunofluorescence and immunoblot analyses with antibody against the major fimbrial subunit AafA of aggregative adherence fimbriae vaariant II (AAF/II) established that the numbers of AAF/II filaments on bacteria grown in the presence of NTZ were dramatically reduced. Comparative quantitative reverse transcription-PCR and reporter gene fusions ( aafA :: phoA ) indicated that aafA expression was unaffected by NTZ, while aggR transcript levels and aggR :: lacZ expression were increased ∼10- and 2.5-fold, respectively, compared with that for the untreated controls. More generally, NTZ inhibited hemagglutination (HA) of red blood cells by the non-biofilm-producing strain JM221 expressing either AAF/I or type I fimbriae. Our findings suggest that the inhibitory action of NTZ on biofilm formation and HA is likely due to inhibition of fimbrial assembly. Antimicrobial agents that inhibit the assembly or function of fimbrial filaments should be good candidates for the prevention of infection.

Most solid tumors originate from epithelial cells, and their metastasis represents the major cause of death among cancer patients. Because each tumor contains many mutations, it has been difficult to isolate how individual genetic events contribute to a tumor cell's ability to disseminate. Two posited mechanisms for metastasis are loss of cell-cell adhesion and activation of an epithelial-mesenchymal transition (EMT). These molecular models converge on the cell adhesion gene E-cadherin (Cdh1). E-cadherin is frequently mutated in human cancers, and it can also be transcriptionally repressed during EMT. In turn, expression of EMT transcription factors in multiple epithelial cancers has been correlated with increased invasion and metastasis. However, the acute consequences of E-cadherin loss or EMT activator expression in otherwise normal epithelial tissues remain incompletely understood. We therefore utilized a combination of organotypic culture, Cre-lox based gene deletion, inducible expression systems, and time-lapse imaging to test the sufficiency of single genetic perturbations to induce dissemination in primary murine mammary epithelium. E-cadherin deletion induced loss of simple epithelial architecture and inhibited branching morphogenesis in 3D culture and in vivo. Furthermore, E-cadherin loss acutely induced collective invasion past basement membrane. However, E-cadherin- cells remained non-protrusive, adhered to one another, and rarely disseminated. Conversely, expression of the EMT transcription factor Twist1 induced rapid dissemination of individual epithelial cells into the extracellular matrix (ECM), and disseminated cells proliferated to form secondary sites. Surprisingly, Twist1+ cells were observed to have membrane-localized E-cadherin during dissemination and during migration in the ECM. Our data thus provide distinct roles for E-cadherin and Twist1 in the early cellular processes of metastasis. We are currently testing whether shRNA knockdown of E-cadherin synergizes with Twist1 to further enhance dissemination. To date, we have demonstrated the sufficiency of constitutive Twist1 expression to induce dissemination of both major mammary cell types: inner luminal epithelial cells and outer myoepithelial cells. Moreover, we observe abnormal localization of myoepithelial cells and basement membrane to the inside of the tissue. However, it remains unclear why some Twist1-expressing cells disseminate while many others remain in the epithelium. We hypothesize that intrinsic, cell type-specific factors influence disseminative capacity. We next seek to test the sufficiency of Twist1 to induce cell dissemination and secondary site formation in distinct mammary epithelial subpopulations. We have developed mouse models that use cell-type specific promoters to drive Twist1 expression in myoepithelial, luminal progenitor, and differentiated luminal lineages. We anticipate that differences across cell types may help identify the subpopulations within a heterogeneous tumor with the highest metastatic potential. Furthermore, we expect that extrinsic factors, such as normal myoepithelial cells, may restrict dissemination of Twist1-expressing luminal cells. Understanding such modulation of Twist1's phenotypic outcomes could suggest new approaches to suppressing metastasis without necessitating direct inhibition of Twist1, itself an “undruggable” target. Citation Format: Eliah R. Shamir, Phuoc T. Tran, Andrew J. Ewald. Building a novel molecular model for Twist1-induced epithelial dissemination. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C39.