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Browsing Journal Articles, BioMed Central and SpringerOpen by Department "Biomedical Engineering and Mechanics"
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- Ablation outcome of irreversible electroporation on potato monitored by impedance spectrum under multi-electrode systemZhao, Yajun; Liu, Hongmei; Bhonsle, Suyashree P.; Wang, Yilin; Davalos, Rafael V.; Yao, Chenguo (2018-09-20)Background Irreversible electroporation (IRE) therapy relies on pulsed electric fields to non-thermally ablate cancerous tissue. Methods for evaluating IRE ablation in situ are critical to assessing treatment outcome. Analyzing changes in tissue impedance caused by electroporation has been proposed as a method for quantifying IRE ablation. In this paper, we assess the hypothesis that irreversible electroporation ablation outcome can be monitored using the impedance change measured by the electrode pairs not in use, getting more information about the ablation size in different directions. Methods Using a square four-electrode configuration, the two diagonal electrodes were used to electroporate potato tissue. Next, the impedance changes, before and after treatment, were measured from different electrode pairs and the impedance information was extracted by fitting the data to an equivalent circuit model. Finally, we correlated the change of impedance from various electrode pairs to the ablation geometry through the use of fitted functions; then these functions were used to predict the ablation size and compared to the numerical simulation results. Results The change in impedance from the electrodes used to apply pulses is larger and has higher deviation than the other electrode pairs. The ablation size and the change in resistance in the circuit model correlate with various linear functions. The coefficients of determination for the three functions are 0.8121, 0.8188 and 0.8691, respectively, showing satisfactory agreement. The functions can well predict the ablation size under different pulse numbers, and in some directions it did even better than the numerical simulation method, which used different electric field thresholds for different pulse numbers. Conclusions The relative change in tissue impedance measured from the non-energized electrodes can be used to assess ablation size during treatment with IRE according to linear functions.
- Allele-specific methylation in the FADS genomic region in DNA from human saliva, CD4+ cells, and total leukocytesRahbar, Elaheh; Waits, Charlotte M. K.; Kirby, Edward H.; Miller, Leslie R.; Ainsworth, Hannah C.; Cui, Tao; Sergeant, Susan; Howard, Timothy D.; Langefeld, Carl D.; Chilton, Floyd H. (2018-04-06)Background Genetic variants within the fatty acid desaturase (FADS) gene cluster (human Chr11) are important regulators of long-chain (LC) polyunsaturated fatty acid (PUFA) biosynthesis in the liver and consequently have been associated with circulating LC-PUFA levels. More recently, epigenetic modifications such as DNA methylation, particularly within the FADS cluster, have been shown to affect LC-PUFA levels. Our lab previously demonstrated strong associations of allele-specific methylation (ASM) between a single nucleotide polymorphism (SNP) rs174537 and CpG sites across the FADS region in human liver tissues. Given that epigenetic signatures are tissue-specific, we aimed to evaluate the methylation status and ASM associations between rs174537 and DNA methylation obtained from human saliva, CD4+ cells and total leukocytes derived from whole blood. The goals were to (1) determine if DNA methylation from these peripheral samples would display similar ASM trends as previously observed in human liver tissues and (2) evaluate the associations between DNA methylation and circulating LC-PUFAs. Results DNA methylation at six CpG sites spanning FADS1 and FADS2 promoter regions and a putative FADS enhancer region were determined in two Caucasian cohorts of healthy volunteers: leukocytes in cohort 1 (n = 89, median age = 43, 35% male) and saliva and CD4+ cells in cohort 2 (n = 32, median age = 41, 41% male). Significant ASM between rs174537 and DNA methylation at three CpG sites located in the FADS2 promoter region (i.e., chr11:61594865, chr11:61594876, chr11:61594907) and one CpG site in the putative enhancer region (chr11:61587979) were observed with leukocytes. In CD4+ cells, significant ASM was observed at CpG sites chr11:61594876 and chr11:61584894. Genotype at rs174537 was significantly associated with DNA methylation from leukocytes. Similar trends were observed with CD4+ cells, but not with saliva. DNA methylation from leukocytes and CD4+ cells also significantly correlated with circulating omega-6 LC-PUFAs. Conclusions We observed significant ASM between rs174537 and DNA methylation at key regulatory regions in the FADS region from leukocyte and CD4+ cells. DNA methylation from leukocytes also correlated with circulating omega-6 LC-PUFAs. These results support the use of peripheral whole blood samples, with leukocytes showing the most promise for future nutrigenomic studies evaluating epigenetic modifications affecting LC-PUFA biosynthesis in humans.
- Docetaxel facilitates lymphatic-tumor crosstalk to promote lymphangiogenesis and cancer progressionHarris, Alexandra R.; Perez, Matthew J.; Munson, Jennifer M. (2018-07-06)Background Infiltration into lymphatic vessels is a critical step in breast cancer metastasis. Lymphatics undergo changes that facilitate metastasis as a result of activation of the cells lining lymphatic vessels, lymphatic endothelial cells (LECs). Inhibition of activation by targeting VEGFR3 can reduce invasion toward lymphatics. To best benefit patients, this approach should be coupled with standard of care that slows tumor growth, such as chemotherapy. Little is known about how chemotherapies, like docetaxel, may influence lymphatics and conversely, how lymphatics can alter responses to therapy. Methods A novel 3D in vitro co-culture model of the human breast tumor microenvironment was employed to examine the contribution of LECs to tumor invasion and viability with docetaxel and anti-VEGFR3, using three cell lines, MDA-MB-231, HCC38, and HCC1806. In vivo, the 4T1 mouse model of breast carcinoma was used to examine the efficacy of combinatorial therapy with docetaxel and anti-VEGFR3 on lymph node metastasis and tumor growth. Lymphangiogenesis in these mice was analyzed by immunohistochemistry and flow cytometry. Luminex analysis was used to measure expression of lymphangiogenic cytokines. Results In vitro, tumor cell invasion significantly increased with docetaxel when LECs were present; this effect was attenuated by inhibition of VEGFR3. LECs reduced docetaxel-induced cell death independent of VEGFR3. In vivo, docetaxel significantly increased breast cancer metastasis to the lymph node. Docetaxel and anti-VEGFR3 combination therapy reduced lymph node and lung metastasis in 4T1 and synergized to reduce tumor growth. Docetaxel induced VEGFR3-dependent vessel enlargement, lymphangiogenesis, and expansion of the LEC population in the peritumoral microenvironment, but not tumor-free stroma. Docetaxel caused an upregulation in pro-lymphangiogenic factors including VEGFC and TNF-α in the tumor microenvironment in vivo. Conclusions Here we present a counter-therapeutic effect of docetaxel chemotherapy that triggers cancer cells to elicit lymphangiogenesis. In turn, lymphatics reduce cancer response to docetaxel by altering the cytokine milieu in breast cancer. These changes lead to an increase in tumor cell invasion and survival under docetaxel treatment, ultimately reducing docetaxel efficacy. These docetaxel-induced effects can be mitigated by anti-VEGFR3 therapy, resulting in a synergism between these treatments that reduces tumor growth and metastasis.
- Microvascular bioengineering: a focus on pericytesZhao, Huaning; Chappell, John C. (2019-03-29)Capillaries within the microcirculation are essential for oxygen delivery and nutrient/waste exchange, among other critical functions. Microvascular bioengineering approaches have sought to recapitulate many key features of these capillary networks, with an increasing appreciation for the necessity of incorporating vascular pericytes. Here, we briefly review established and more recent insights into important aspects of pericyte identification and function within the microvasculature. We then consider the importance of including vascular pericytes in various bioengineered microvessel platforms including 3D culturing and microfluidic systems. We also discuss how vascular pericytes are a vital component in the construction of computational models that simulate microcirculation phenomena including angiogenesis, microvascular biomechanics, and kinetics of exchange across the vessel wall. In reviewing these topics, we highlight the notion that incorporating pericytes into microvascular bioengineering applications will increase their utility and accelerate the translation of basic discoveries to clinical solutions for vascular-related pathologies.
- Perturbation-based balance training targeting both slip- and trip-induced falls among older adults: a randomized controlled trialAllin, Leigh J.; Brolinson, Per Gunnar; Beach, Briana M.; Kim, Sunwook; Nussbaum, Maury A.; Roberto, Karen A.; Madigan, Michael L. (2020-06-12)Background Falls are the leading cause of injuries among older adults. Perturbation-based balance training (PBT) is an innovative approach to fall prevention that aims to improve the reactive balance response following perturbations such as slipping and tripping. Many of these PBT studies have targeted reactive balance after slipping or tripping, despite both contributing to a large proportion of older adult falls. The goal of this randomized controlled trial was to evaluate the effects of PBT targeting slipping and tripping on laboratory-induced slips and trips. To build upon prior work, the present study included: 1) a control group; 2) separate training and assessment sessions; 3) PBT methods potentially more amenable for use outside the lab compared to methods employed elsewhere, and 4) individualized training for older adult participants. Methods Thirty-four community-dwelling, healthy older adults (61–75 years) were assigned to PBT or a control intervention using minimization. Using a parallel design, reactive balance (primary outcome) and fall incidence were assessed before and after four sessions of BRT or a control intervention involving general balance exercises. Assessments involved exposing participants to an unexpected laboratory-induced slip or trip. Reactive balance and fall incidence were compared between three mutually-exclusive groups: 1) baseline participants who experienced a slip (or trip) before either intervention, 2) post-control participants who experienced a slip (or trip) after the control intervention, and 3) post-PBT participants who experienced a slip (or trip) after PBT. Neither the participants nor investigators were blinded to group assignment. Results All 34 participants completed all four sessions of their assigned intervention, and all 34 participants were analyzed. Regarding slips, several measures of reactive balance were improved among post-PBT participants when compared to baseline participants or post-control participants, and fall incidence among post-PBT participants (18%) was lower than among baseline participants (80%). Regarding trips, neither reactive balance nor fall incidence differed between groups Conclusions PBT targeting slipping and tripping improved reactive balance and fall incidence after laboratory-induced slips. Improvements were not observed after laboratory-induced trips. The disparity in efficacy between slips and trip may have resulted from differences in dosage and specificity between slip and trip training. Trial registration Name of Clinical Trial Registry: clinicaltrials.gov Trial Registration number: NCT04308239. Date of Registration: March 13, 2020 (retrospectively registered).
- Review of, "Biostatistics and Epidemiology" by S. Wassertheil-SmollerSchneck, Daniel J. (2004-10-19)The entire book review is in the form of an abstract ... some 400 words or less.