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1. Protocol for electrotaxis of large epithelial cell sheets

Author

Zhang, Yan, Lee, Rachel M, Zhu, Zijie, Sun, Yaohui, Zhu, Kan, Xu, Zhengping, Lin, Francis, Pan, Tingrui, Losert, Wolfgang, and Zhao, Min

Subjects
Biochemistry and Cell Biology, Biological Sciences, Biophysics, Biotechnology and bioengineering, Cell Biology, Cell-based Assays, Microscopy, Tissue Engineering
Abstract

Here, we present a protocol for electrotaxis of large epithelial cell sheets without compromising the integrity of cell epithelia in a high-throughput customized directed current electrotaxis chamber. We describe the fabrication and use of polydimethylsiloxane stencils to control the size and shape of human keratinocyte cell sheets. We detail cell tracking, cell sheet contour assay, and particle image velocimetry to reveal the spatial and temporal motility dynamics of cell sheets. This approach is applicable to other collective cell migration studies. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022).1.

Published
2023

2. Propagation dynamics of electrotactic motility in large epithelial cell sheets

Author

Zhang, Yan, Xu, Guoqing, Wu, Jiandong, Lee, Rachel M, Zhu, Zijie, Sun, Yaohui, Zhu, Kan, Losert, Wolfgang, Liao, Simon, Zhang, Gong, Pan, Tingrui, Xu, Zhengping, Lin, Francis, and Zhao, Min

Subjects
Biochemistry and Cell Biology, Engineering, Biological Sciences, Biomedical Engineering, Bioengineering, Stem Cell Research, Biological sciences, Cell biology, Functional aspects of cell biology, Systems biology
Abstract

Directional migration initiated at the wound edge leads epithelia to migrate in wound healing. How such coherent migration is achieved is not well understood. Here, we used electric fields to induce robust migration of sheets of human keratinocytes and developed an in silico model to characterize initiation and propagation of epithelial collective migration. Electric fields initiate an increase in migration directionality and speed at the leading edge. The increases propagate across the epithelial sheets, resulting in directional migration of cell sheets as coherent units. Both the experimental and in silico models demonstrated vector-like integration of the electric and default directional cues at free edge in space and time. The resultant collective migration is consistent in experiments and modeling, both qualitatively and quantitatively. The keratinocyte model thus faithfully reflects key features of epithelial migration as a coherent tissue in vivo, e.g. that leading cells lead, and that epithelium maintains cell-cell junction.

Published
2022

3. Diagnostic laparoscopy is underutilized in the staging of gastric adenocarcinoma regardless of hospital type: An US safety net collaborative analysis

Author

Macek, Aleeza J Leder, Wang, Annie, Turgeon, Michael K, Lee, Rachel M, Russell, Maria C, Porembka, Matthew R, Alterio, Rodrigo, Ju, Michelle, Kronenfeld, Joshua, Goel, Neha, Datta, Jashodeep, Maker, Ajay V, Fernandez, Manuel, Richter, Harry, Berman, Russell S, Correa‐Gallego, Camilo, and Lee, Ann Y

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Cancer, Clinical Research, Rare Diseases, Patient Safety, No Poverty, Adenocarcinoma, Hospitals, Humans, Laparoscopy, Neoplasm Staging, Retrospective Studies, Stomach Neoplasms, diagnostic laparoscopy, disparities, gastric adenocarcinoma, safety net hospital, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundDiagnostic laparoscopy (DL) is a key component of staging for locally advanced gastric adenocarcinoma (GA). We hypothesized that utilization of DL varied between safety net (SNH) and affiliated tertiary referral centers (TRCs).MethodsPatients diagnosed with primary GA eligible for DL were identified from the US Safety Net Collaborative database (2012-2014). Clinicopathologic factors were analyzed for association with use of DL and findings on DL. Overall survival (OS) was analyzed by Kaplan-Meier method.ResultsAmong 233 eligible patients, 69 (30%) received DL, of which 24 (35%) were positive for metastatic disease. Forty percent of eligible SNH patients underwent DL compared to 21.5% at TRCs. Lack of insurance was significantly associated with decreased use of DL (OR 0.48, p

Published
2022

8. Clinical Presentation Patterns and Survival Outcomes of Hispanic Patients with Gastric Cancer

Author

Vitiello, Gerardo A, Hani, Leena, Wang, Annie, Porembka, Matthew R, Alterio, Rodrigo, Ju, Michelle, Turgeon, Michael K, Lee, Rachel M, Russell, Maria C, Kronenfeld, Joshua, Goel, Neha, Datta, Jashodeep, Maker, Ajay V, Fernandez, Manuel, Richter, Harry, Correa-Gallego, Camilo, Berman, Russell S, and Lee, Ann Y

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Patient Safety, Rare Diseases, Cancer, Clinical Trials and Supportive Activities, Health Services, Clinical Research, No Poverty, Ethnicity, Hispanic or Latino, Humans, Middle Aged, Neoplasm Staging, Retrospective Studies, Stomach Neoplasms, Gastric cancer, Hispanic, Safety-net, Survival, Clinical Sciences, Surgery, Clinical sciences
Abstract

BackgroundHispanic patients have a higher incidence of gastric cancer when compared to non-Hispanics. Outlining clinicodemographic characteristics and assessing the impact of ethnicity on stage-specific survival may identify opportunities to improve gastric cancer care for this population.MethodsPatients with gastric cancer in the US Safety Net Collaborative (2012-2014) were retrospectively reviewed. Demographics, clinicopathologic characteristics, operative details, and outcomes were compared between Hispanic and non-Hispanic patients. Early onset gastric cancer was defined as age

Published
2021

9. Is there a difference in utilization of a perioperative treatment approach for gastric cancer between safety net hospitals and tertiary referral centers?

Author

Turgeon, Michael K, Lee, Rachel M, Keilson, Jessica M, Ju, Michelle R, Porembka, Matthew R, Alterio, Rodrigo E, Kronenfeld, Joshua, Datta, Jashodeep, Goel, Neha, Wang, Annie, Lee, Ann Y, Fernandez, Manuel, Richter, Harry, Maker, Ajay V, Maithel, Shishir K, and Russell, Maria C

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Cancer, Clinical Research, Digestive Diseases, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Aged, Female, Follow-Up Studies, Gastrectomy, Humans, Male, Middle Aged, Neoadjuvant Therapy, Perioperative Care, Prognosis, Quality of Health Care, Retrospective Studies, Safety-net Providers, Stomach Neoplasms, Tertiary Care Centers, gastric cancer, health disparities, perioperative therapy, safety net hospitals, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Background and objectivesPerioperative therapy is a favored treatment strategy for gastric cancer. We sought to assess utilization of this approach at safety net hospitals (SNH) and tertiary referral centers (TRC).Materials and methodsPatients in the US Safety Net Collaborative (2012-2014) with resectable gastric cancer across five SNH and their sister TRC were included. Primary outcomes were receipt of neoadjuvant chemotherapy (NAC) and perioperative therapy.ResultsOf 284 patients, 36% and 64% received care at SNH and TRC. The distribution of Stage II/III resectable disease was similar across facilities. Receipt of NAC at SNH and TRC was similar (56% vs. 46%, p = 0.27). Compared with overall clinical stage, 38% and 36% were pathologically downstaged at SNH and TRC, respectively. Among patients who received NAC, those who also received adjuvant chemotherapy at SNH and TRC were similar (66% vs. 60%, p = 0.50). Asian race and higher clinical stage were associated with receipt of perioperative therapy (both p

Published
2021

11. A novel preoperative risk score to optimize patient selection for performing concomitant liver resection with cytoreductive surgery/HIPEC

Author

Lee, Rachel M, Gamboa, Adriana C, Turgeon, Michael K, Zaidi, Mohammad Y, Kimbrough, Charles, Leiting, Jennifer, Grotz, Travis, Lee, Andrew J, Fournier, Keith, Powers, Benjamin, Dineen, Sean, Baumgartner, Joel M, Veerapong, Jula, Mogal, Harveshp, Clarke, Callisia, Wilson, Gregory, Patel, Sameer, Hendrix, Ryan, Lambert, Laura, Pokrzywa, Courtney, Abbott, Daniel E, LaRocca, Christopher J, Raoof, Mustafa, Greer, Jonathan, Johnston, Fabian M, Staley, Charles A, Cloyd, Jordan M, Maithel, Shishir K, and Russell, Maria C

Subjects
Clinical Research, Digestive Diseases, Liver Disease, Patient Safety, Colo-Rectal Cancer, Cancer, Evaluation of treatments and therapeutic interventions, 6.4 Surgery, Appendiceal Neoplasms, Chemotherapy, Cancer, Regional Perfusion, Colorectal Neoplasms, Combined Modality Therapy, Cytoreduction Surgical Procedures, Female, Follow-Up Studies, Hepatectomy, Humans, Hyperthermia, Induced, Male, Middle Aged, Patient Selection, Peritoneal Neoplasms, Preoperative Care, Prognosis, Risk Factors, Survival Rate, appendiceal adenocarcinoma, colorectal cancer, HIPEC, liver resection, risk score, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundWhile parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), liver resection (LR) is increasingly performed with CRS/HIPEC.MethodsPatients from the US HIPEC Collaborative (2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival (OS).ResultsA total of 658 patients were included. About 83 (15%) underwent LR of colorectal (58%) or invasive appendiceal (42%) metastases. LR patients had more complications (81% vs. 60%; p = .001), greater number of complications (2.3 vs. 1.5; p

Published
2021

13. Implications of Postoperative Complications for Survival After Cytoreductive Surgery and HIPEC: A Multi-Institutional Analysis of the US HIPEC Collaborative

Author

Gamboa, Adriana C, Lee, Rachel M, Turgeon, Michael K, Zaidi, Mohammad Y, Kimbrough, Charles W, Grotz, Travis E, Leiting, Jennifer, Fournier, Keith, Lee, Andrew J, Dineen, Sean P, Powers, Benjamin D, Veerapong, Jula, Baumgartner, Joel M, Clarke, Callisia N, Mogal, Harveshp, Patel, Sameer H, Lee, Tiffany C, Lambert, Laura A, Hendrix, Ryan J, Abbott, Daniel E, Pokrzywa, Courtney, Raoof, Mustafa, Eng, Oliver S, Johnston, Fabian M, Greer, Jonathan, Cloyd, Jordan M, Maithel, Shishir K, and Staley, Charles A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Colo-Rectal Cancer, Clinical Research, Cancer, Good Health and Well Being, Aged, Antineoplastic Combined Chemotherapy Protocols, Appendiceal Neoplasms, Cytoreduction Surgical Procedures, Female, Humans, Hyperthermic Intraperitoneal Chemotherapy, Male, Middle Aged, Peritoneal Neoplasms, Postoperative Complications, Retrospective Studies, Survival Rate, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundPostoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on the survival of patients with appendiceal or colorectal cancer after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is unknown.MethodsThe US HIPEC Collaborative (2000-2017) was reviewed for patients who underwent CCR0/1 CRS/HIPEC for appendiceal/colorectal cancer. The analysis was stratified by noninvasive appendiceal neoplasm versus invasive appendiceal/colorectal adenocarcinoma. The POCs were grouped into infectious, cardiopulmonary, thromboembolic, and intestinal dysmotility. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS).ResultsOf the 1304 patients, 33% had noninvasive appendiceal neoplasm (n = 426), and 67% had invasive appendiceal/colorectal adenocarcinoma (n = 878). In the noninvasive appendiceal cohort, POCs were identified in 55% of the patients (n = 233). The 3-year OS and RFS did not differ between the patients who experienced a complication and those who did not (OS, 94% vs 94%, p = 0.26; RFS, 68% vs 60%, p = 0.15). In the invasive appendiceal/colorectal adenocarcinoma cohort, however, POCs (63%; n = 555) were associated with decreased 3-year OS (59% vs 74%; p

Published
2020

21. Collective cell migration has distinct directionality and speed dynamics

Author

Zhang, Yan, Xu, Guoqing, Lee, Rachel M, Zhu, Zijie, Wu, Jiandong, Liao, Simon, Zhang, Gong, Sun, Yaohui, Mogilner, Alex, Losert, Wolfgang, Pan, Tingrui, Lin, Francis, Xu, Zhengping, and Zhao, Min

Subjects
Biochemistry and Cell Biology, Biological Sciences, 1.1 Normal biological development and functioning, Biocompatible Materials, Calcium, Cell Communication, Cell Count, Cell Line, Cell Movement, Dimethylpolysiloxanes, Epithelium, Corneal, Humans, Models, Biological, Wound Healing, Wound healing, Cell contractility, PDMS, Corneal epithelial cell, Cell communication, Blebbistatin, Physiology, Clinical Sciences, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medical biochemistry and metabolomics, Oncology and carcinogenesis
Abstract

When a constraint is removed, confluent cells migrate directionally into the available space. How the migration directionality and speed increase are initiated at the leading edge and propagate into neighboring cells are not well understood. Using a quantitative visualization technique-Particle Image Velocimetry (PIV)-we revealed that migration directionality and speed had strikingly different dynamics. Migration directionality increases as a wave propagating from the leading edge into the cell sheet, while the increase in cell migration speed is maintained only at the leading edge. The overall directionality steadily increases with time as cells migrate into the cell-free space, but migration speed remains largely the same. A particle-based compass (PBC) model suggests cellular interplay (which depends on cell-cell distance) and migration speed are sufficient to capture the dynamics of migration directionality revealed experimentally. Extracellular Ca2+ regulated both migration speed and directionality, but in a significantly different way, suggested by the correlation between directionality and speed only in some dynamic ranges. Our experimental and modeling results reveal distinct directionality and speed dynamics in collective migration, and these factors can be regulated by extracellular Ca2+ through cellular interplay. Quantitative visualization using PIV and our PBC model thus provide a powerful approach to dissect the mechanisms of collective cell migration.

Published
2017

27. A closer look at the natural history and recurrence patterns of high-grade truncal/extremity leiomyosarcomas: A multi-institutional analysis from the US Sarcoma Collaborative

Author

Lee, Rachel M., Ethun, Cecilia G., Zaidi, Mohammad Y., Tran, Thuy B., Poultsides, George A., Grignol, Valerie P., Howard, John H., Bedi, Meena, Gamblin, T. Clark, Tseng, Jennifer, Roggin, Kevin K., Chouliaras, Konstantinos, Votanopoulos, Konstantinos, Krasnick, Bradley A., Fields, Ryan C., Oskouei, Shervin V., Monson, David K., Reimer, Nickolas B., Maithel, Shishir K., and Cardona, Kenneth

Published
2020
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31. What is the Optimal Preoperative Imaging Modality for Assessing Peritoneal Cancer Index? An Analysis From the United States HIPEC Collaborative

Author

Lee, Rachel M., Zaidi, Mohammad Y., Gamboa, Adriana C., Speegle, Shelby, Kimbrough, Charles W., Cloyd, Jordan M., Leiting, Jennifer L., Grotz, Travis E., Lee, Andrew J., Fournier, Keith F., Powers, Benjamin D., Dineen, Sean P., Baumgartner, Joel, Veerapong, Jula, Clarke, Callisia N., Sussman, Jeffrey J., Patel, Sameer, Hendrix, Ryan J., Lambert, Laura A., Vande Walle, Kara A., Abbott, Daniel E., LaRocca, Christopher J., Raoof, Mustafa, Fackche, Nadege, Johnston, Fabian M., Staley, Charles A., Maithel, Shishir K., and Russell, Maria C.

Published
2020
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35. The Intersection of Age and Tumor Biology with Postoperative Outcomes in Patients After Cytoreductive Surgery and HIPEC

Author

Turgeon, Michael K., Gamboa, Adriana C., Lee, Rachel M., Zaidi, Mohammad Y., Kimbrough, Charles, Grotz, Travis, Fournier, Keith, Powers, Benjamin, Dineen, Sean, Veerapong, Jula, Clarke, Callisia, Mogal, Harveshp, Patel, Sameer H., Lambert, Laura, Ronnekleiv-Kelly, Sean, Raoof, Mustafa, Fackche, Nadege, Greer, Jonathan B., Staley, Charles A., Cloyd, Jordan M., Maithel, Shishir K., and Winer, Joshua H.

Published
2020
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36. Quantifying stretching and rearrangement in epithelial sheet migration

Author

Lee, Rachel M., Kelley, Douglas H., Nordstrom, Kerstin N., Ouellette, Nicholas T., and Losert, Wolfgang

Subjects
Physics - Biological Physics, Quantitative Biology - Cell Behavior
Abstract

Although understanding the collective migration of cells, such as that seen in epithelial sheets, is essential for understanding diseases such as metastatic cancer, this motion is not yet as well characterized as individual cell migration. Here we adapt quantitative metrics used to characterize the flow and deformation of soft matter to contrast different types of motion within a migrating sheet of cells. Using a Finite-Time Lyapunov Exponent (FTLE) analysis, we find that - in spite of large fluctuations - the flow field of an epithelial cell sheet is not chaotic. Stretching of a sheet of cells (i.e., positive FTLE) is localized at the leading edge of migration. By decomposing the motion of the cells into affine and non-affine components using the metric D$^{2}_{min}$, we quantify local plastic rearrangements and describe the motion of a group of cells in a novel way. We find an increase in plastic rearrangements with increasing cell densities, whereas inanimate systems tend to exhibit less non-affine rearrangements with increasing density., Comment: 21 pages, 7 figures This is an author-created, un-copyedited version of an article accepted for publication in the New Journal of Physics. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at doi:10.1088/1367-2630/15/2/025036

Published
2013
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42. Seasonal abundance, lipid storage, and energy density of Calanus finmarchicus and other copepod preyfields along the Northwest Atlantic continental shelf.

Author

Lee, Rachel M Carlowicz, Keiling, Toniann D, and Warren, Joseph D

Subjects
*CALANUS finmarchicus, *ENERGY density, *ENERGY storage, *SPRING, *SEASONS, *LIPIDS
Abstract

Calanus finmarchicus is an abundant calanoid copepod in the New York Bight (NYB) that has energy-dense lipid stores. This study measured C. finmarchicus abundance, lipid storage and energy density and compared it to two other abundant calanoid species in the region. We compared the NYB C. finmarchicus preyfield characteristics with data from two other NW Atlantic coastal ecosystems, the Gulf of Maine (GoM) and Cape Cod Bay (CCB). Copepods from net tows were identified, enumerated, photographed and measured. These data were used to calculate animal biovolume and lipid content as well as the volumetric energy density of the copepod preyfield. C. finmarchicus were most abundant in spring and summer and the mean lipid storage of C. finmarchicus remained largely constant regardless of season and location within the NYB. Centropages typicus were abundant enough in the winter to be more energy-rich than C. finmarchicus. Temora longicornis, while also abundant, never surpassed the energy density of C. finmarchicus. C. finmarchicus in the NYB were comparably lipid-rich to those from the GoM and CCB. C. finmarchicus in the NYB can be a reliable energy source for local predators due to their high spring and summer abundances and year-round storage of high-energy wax esters. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Optimal Surveillance Frequency After CRS/HIPEC for Appendiceal and Colorectal Neoplasms: A Multi-institutional Analysis of the US HIPEC Collaborative

Author

Gamboa, Adriana C., Zaidi, Mohammad Y., Lee, Rachel M., Speegle, Shelby, Switchenko, Jeffrey M., Lipscomb, Joseph, Cloyd, Jordan M., Ahmed, Ahmed, Grotz, Travis, Leiting, Jennifer, Fournier, Keith, Lee, Andrew J., Dineen, Sean, Powers, Benjamin D., Lowy, Andrew M., Kotha, Nikhil V., Clarke, Callisia, Gamblin, T. Clark, Patel, Sameer H., Lee, Tiffany C., Lambert, Laura, Hendrix, Ryan J., Abbott, Daniel E., Vande Walle, Kara, Lafaro, Kelly, Lee, Byrne, Johnston, Fabian M., Greer, Jonathan, Russell, Maria C., Staley, Charles A., and Maithel, Shishir K.

Published
2020
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47. Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative

Author

Zaidi, Mohammad Y., Lee, Rachel M., Gamboa, Adriana C., Speegle, Shelby, Cloyd, Jordan M., Kimbrough, Charles, Grotz, Travis, Leiting, Jennifer, Fournier, Keith, Lee, Andrew J., Dineen, Sean, Dessureault, Sophie, Kelly, Kaitlyn J., Kotha, Nikhil V., Clarke, Callisia, Gamblin, T. Clark, Patel, Sameer H., Lee, Tiffany C., Hendrix, Ryan J., Lambert, Laura, Ronnekleiv-Kelly, Sean, Pokrzywa, Courtney, Blakely, Andrew M., Lee, Byrne, Johnston, Fabian M., Fackche, Nadege, Russell, Maria C., Maithel, Shishir K., and Staley, III, Charles A.

Published
2020
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