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New Haven, CT, United States

Devita V.T.,Yale Comprehensive Cancer Center | Eggermont A.M.M.,Cancer Institute | Hellman S.,University of Chicago | Kerr D.J.,University of Oxford
Nature Reviews Clinical Oncology

In the past decade, we have witnessed unprecedented changes and some remarkable advances that have enabled true personalized medicine. Nevertheless, many challenges in clinical cancer research remain and need to be overcome if we are to witness similar progress in the next decade. Such hurdles include, but are not limited to, clinical development and testing of multiple agents in combination, design of clinical trials to best accommodate the ever increasing knowledge of heterogeneity of the disease, regulatory challenges relating to drug development and trial design, and funding for basic research. With this in mind, we asked four leading cancer researchers from around the world, and who have been associated with the journal since its launch in November 2004 what, in their opinion, we have learnt over the past 10 years and how we should progress in the next 10 years. © 2014 Macmillan Publishers Limited. All rights reserved. Source

Lee S.-K.,Chung - Ang University | Kim D.-J.,Chonbuk National University | Lee G.,Chung - Ang University | Kim G.-S.,Chonbuk National University | And 3 more authors.
Biosensors and Bioelectronics

We report on the rapid and direct quantification of specific cell captures using a micro-patterned streptavidin (STR)-functionalized silicon nanowire (SiNW) platform, which was prepared by Ag-assisted wet chemical etching and a photo-lithography process. This platform operates by high-affinity cell capture rendered by the combination of antibody-epithelial cell surface-binding, biotin-streptavidin binding, and the topologically enhanced cell-substrate interaction on a 3-dimensional SiNWs array. In this work, we developed a micro-patterned nanowire platform, with which we were able to directly evaluate the performance enhancement due to nanotopography. An excellent capture efficiency of ~96.6±6.7%, which is the highest value achieved thus far for the targeting specific A549 cells on a selective area of patterned SiNWs, is demonstrated. Direct comparison between the nanowire region and the planar region on the same substrate indicates dramatically elevated cell-capture efficiency on nanotopological surface identical surface chemistry (<2% cell-capture efficiency). An excellent linear response was seen for quantifying captured A549 cells with respect to loaded cells. This study suggests that the micro-patterned STR-functionalized SiNWs platform provides additional advantage for detecting rare cells populations in a more quantitative and specific manner. © 2013 Elsevier B.V. Source

Licurse A.,Yale University | Barber E.,Yale University | Joffe S.,Harvard University | Gross C.,Yale University | Gross C.,Yale Comprehensive Cancer Center
Archives of Internal Medicine

Background: Despite increased demand for disclosure of physician and researcher financial ties (FTs) to industry, little is known about patients', research participants', or journal readers' attitudes toward FTs. Methods: We systematically reviewed original, quantitative studies of patients', research participants', or journal readers' views about FTs to pharmaceutical and medical device companies. The MEDLINE, Scopus, and Web of Knowledge databases were searched for English-language studies containing original, quantitative data on attitudes toward FTs. We screened 6561 citations and retrieved 244 potentially eligible abstracts. Of these, 20 met inclusion criteria. Results: Eleven studies assessed FTs and perceptions of quality. In clinical care, patients believed FTs decreased the quality and increased the cost of care. In research, FTs affected perceptions of study quality. In 2 studies, readers' perceptions of journal article quality decreased after disclosure of FTs. Eight studies assessed the acceptability of FTs. Patients were more likely to view personal gifts to physicians as unacceptable, compared with professional gifts. In 6 of the 10 studies that assessed the importance of disclosure, most patients and research participants believed FTs should be disclosed; in the other 4, approximately one-quarter believed FTs should be disclosed. Among the 7 studies assessing willingness to participate in research, approximately one-quarter of participants reported less willingness after disclosure of FTs. Conclusions: Patients believe that FTs influence professional behavior and should be disclosed. Patients, physicians, and research participants believe FTs decrease the quality of research evidence, and, for some, knowledge of FTs would affect willingness to participate in research. ©2010 American Medical Association. All rights reserved. Source

Zhou J.,Yale University | Wu Y.,Yale University | Lee S.-K.,Yale University | Lee S.-K.,Chonbuk National University | And 2 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology

High-content cellomic analysis is a powerful tool for rapid screening of cellular responses to extracellular cues and examination of intracellular signal transduction pathways at the single-cell level. In conjunction with microfluidics technology that provides unique advantages in sample processing and precise control of fluid delivery, it holds great potential to transform lab-on-a-chip systems for high-throughput cellular analysis. However, high-content imaging instruments are expensive, sophisticated, and not readily accessible. Herein, we report on a laser scanning cytometry approach that exploits a bench-top microarray scanner as an end-point reader to perform rapid and automated fluorescence imaging of cells cultured on a chip. Using high-content imaging analysis algorithms, we demonstrated multiplexed measurements of morphometric and proteomic parameters from all single cells. Our approach shows the improvement of both sensitivity and dynamic range by two orders of magnitude as compared to conventional epifluorescence microscopy. We applied this technology to high-throughput analysis of mesenchymal stem cells on an extracellular matrix protein array and characterization of heterotypic cell populations. This work demonstrates the feasibility of a laser microarray scanner for high-content cellomic analysis and opens up new opportunities to conduct informative cellular analysis and cell-based screening in the lab-on-a-chip systems. © The Royal Society of Chemistry 2012. Source

Lee S.-K.,Yale University | Lee S.-K.,Chonbuk National University | Kim G.-S.,Chonbuk National University | Wu Y.,Yale University | And 11 more authors.
Nano Letters

We report on the development of a nanowire substrate-enabled laser scanning imaging cytometry for rare cell analysis in order to achieve quantitative, automated, and functional evaluation of circulating tumor cells. Immuno-functionalized nanowire arrays have been demonstrated as a superior material to capture rare cells from heterogeneous cell populations. The laser scanning cytometry method enables large-area, automated quantitation of captured cells and rapid evaluation of functional cellular parameters (e.g., size, shape, and signaling protein) at the single-cell level. This integrated platform was first tested for capture and quantitation of human lung carcinoma cells from a mixture of tumor cells and leukocytes. We further applied it to the analysis of rare tumor cells spiked in fresh human whole blood (several cells per mL) that emulate metastatic cancer patient blood and demonstrated the potential of this technology for analyzing circulating tumor cells in the clinical settings. Using a high-content image analysis algorithm, cellular morphometric parameters and fluorescence intensities can be rapidly quantitated in an automated, unbiased, and standardized manner. Together, this approach enables informative characterization of captured cells in situ and potentially allows for subclassification of circulating tumor cells, a key step toward the identification of true metastasis-initiating cells. Thus, this nanoenabled platform holds great potential for studying the biology of rare tumor cells and for differential diagnosis of cancer progression and metastasis. © 2012 American Chemical Society. Source

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