Journal ArticleAdvanced Therapeutics · November 1, 2024
Nucleic acid vaccines play important roles in the prevention and treatment of diseases. However, limited immunogenicity remains a major obstacle for DNA vaccine applications in the clinic. To address the issue, the present study investigates a cocktail app ...
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Journal ArticleAdvanced drug delivery reviews · July 2024
Nucleic acid technology has revolutionized vaccine development, enabling rapid design and production of RNA and DNA vaccines for prevention and treatment of diseases. The successful deployment of mRNA and plasmid DNA vaccines against COVID-19 has further v ...
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Journal ArticlePharmaceutics · March 29, 2024
Our previous study discovered that sucrose and other non-reducing sugars (e.g., trehalose and raffinose) could be used to improve the electrotransfer (ET) of molecular cargo, including DNA, mRNA, and ribonucleoprotein in various cell lines and primary huma ...
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Journal ArticleCellular and molecular bioengineering · December 2023
IntroductionPlasmid DNA (pDNA) must be delivered into the nucleus for transgene expression in mammalian cells. The entry may happen passively during the nuclear envelope breakdown and reformation in dividing cells or actively through the nuclear p ...
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Journal ArticleProc Natl Acad Sci U S A · October 31, 2023
Nucleic acid vaccines have shown promising results in the clinic against infectious diseases and cancers. To robustly improve the vaccine efficacy and safety, we developed an approach to increase the intracellular stability of nucleic acids by transiently ...
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Journal ArticleBioelectrochemistry (Amsterdam, Netherlands) · October 2023
Electrotransfection is a non-viral method for delivery of nucleic acids into cells. In our previous study, we have determined the minimal copy number of plasmid DNA (pDNA) per cell required for transgene expression post electrotransfection, and developed a ...
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Journal ArticleUltrasonics · September 2023
Recently, surface acoustic wave (SAW) based acoustofluidic separation of microparticles and cells has attracted increasing interest due to accuracy and biocompatibility. Precise control of the input power of acoustofluidic devices is essential for generati ...
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Journal ArticleApplied Acoustics · March 30, 2023
Acoustofluidic techniques are increasingly used to manipulate nano- and micro-particles in microfluidics. A wide range of acoustofluidic devices consisting of microchannels and acoustic sources have been developed for applications in biochemistry and biome ...
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Journal ArticleTransport in Porous Media · March 1, 2023
This work presents a double-permeability poroelasticity model for fluid flows in both the microvascular and interstitial networks in a biological tissue. In the newly developed model, both networks are modeled as porous structures with distinct permeabilit ...
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Journal ArticleFrontiers in bioengineering and biotechnology · January 2023
Introduction: Electrotransfection (ET) is a non-viral approach widely used for delivery of naked nucleic acids. Its efficiency can be increased in vitro by treatment of cells with various small molecule enhancers. However, these enhancers oft ...
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Journal ArticleBioelectrochemistry (Amsterdam, Netherlands) · April 2021
Plasmid DNA (pDNA) has been widely used for non-viral gene delivery. After pDNA molecules enter a mammalian cell, they may be trapped in subcellular structures or degraded by nucleases. Only a fraction of them can function as templates for transcription in ...
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Journal ArticleIEEE Electron Device Letters · April 1, 2021
In recent years, surface acoustic wave (SAW) devices have demonstrated great potentials and increasing applications in the manipulation of nano- and micro-particles including biological cells with the advantages of label-free, high sensitivity and accuracy ...
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Journal ArticleUltrasonics · December 2020
Gallium nitride (GaN) is a compound semiconductor which shows advantages in new functionalities and applications due to its piezoelectric, optoelectronic, and piezo-resistive properties. This study develops a thin film GaN-based acoustic tweezer (GaNAT) us ...
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Journal ArticleMol Cancer Res · October 2020
Soft-tissue sarcomas (STS) are rare malignancies showing lineage differentiation toward diverse mesenchymal tissues. Half of all high-grade STSs develop lung metastasis with a median survival of 15 months. Here, we used a genetically engineered mouse model ...
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Journal ArticleCancers · September 2020
T cell receptor (TCR) knockout is a critical step in producing universal chimeric antigen receptor T cells for cancer immunotherapy. A promising approach to achieving the knockout is to deliver the CRISPR/Cas9 system into cells using electrotransfer techno ...
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Journal ArticleBioelectricity · September 2020
BackgroundPulsed electric field has been widely used to facilitate molecular cargo transfer into cells. However, the cell viability is often decreased when trying to increase the electrotransfer efficiency. We hypothesize that the decrease is due ...
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Journal ArticleAdv Biosyst · August 2020
Cell engineering relies heavily on viral vectors for the delivery of molecular cargo into cells due to their superior efficiency compared to nonviral ones. However, viruses are immunogenic and expensive to manufacture, and have limited delivery capacity. N ...
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Journal ArticleLab on a chip · August 2020
Correction for 'Development and characterisation of acoustofluidic devices using detachable electrodes made from PCB' by Roman Mikhaylov et al., Lab Chip, 2020, 20, 1807-1814, DOI: 10.1039/C9LC01192G. ...
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Journal ArticleIEEE Transactions on Electron Devices · August 1, 2020
Gallium nitride (GaN) is a compound semiconductor which has advantages to generate new functionalities and applications due to its piezoelectric, pyroelectric, and piezo-resistive properties. Recently, surface acoustic wave (SAW)-based acoustic tweezers we ...
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Journal ArticleLab on a chip · May 2020
Acoustofluidics has been increasingly applied in biology, medicine and chemistry due to its versatility in manipulating fluids, cells and nano-/micro-particles. In this paper, we develop a novel and simple technology to fabricate a surface acoustic wave (S ...
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Journal ArticleMicrosc Microanal · October 2018
Emerging evidence from various studies indicates that plasmid DNA (pDNA) is internalized by cells through an endocytosis-like process when it is used for electrotransfection. To provide morphological evidence of the process, we investigated ultrastructures ...
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Journal ArticleMolecular pharmaceutics · September 2018
Electrotransfection (ET) is a nonviral method for delivery of various types of molecules into cells both in vitro and in vivo. Close to 90 clinical trials that involve the use of ET have been performed, and approximately half of them are related to cancer ...
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Journal ArticleNature communications · August 2018
Quantum confined materials have been extensively studied for photoluminescent applications. Due to intrinsic limitations of low biocompatibility and challenging modulation, the utilization of conventional inorganic quantum confined photoluminescent materia ...
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Journal ArticleMolecular therapy. Nucleic acids · June 2018
The nuclear envelope is a physiological barrier to electrogene transfer. To understand different mechanisms of the nuclear entry for electrotransfected plasmid DNA (pDNA), the current study investigated how manipulation of the mechanisms could affect elect ...
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Journal ArticleProgress in neurobiology · October 2017
Although neurons attract the most attention in neurobiology, our current knowledge of neural circuit can only partially explain the neurological and psychiatric conditions of the brain. Thus, it is also important to consider the influence of brain intersti ...
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Journal ArticleJournal of biomechanics · August 2017
Elevation of intraocular pressure has been correlated to changes in stiffness of trabecular meshwork (TM) in glaucomatous eyes although mechanical properties of the TM remain to be quantitatively determined. Data in the literature suggest that the TM canno ...
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Journal ArticleMol Ther · March 1, 2017
Electrotransfection is a widely used method for delivering genes into cells with electric pulses. Although different hypotheses have been proposed, the mechanism of electrotransfection remains controversial. Previous studies have indicated that uptake and ...
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Journal ArticlePloS one · January 2017
A recent theory suggests that endocytosis is involved in uptake and intracellular transport of electrotransfected plasmid DNA (pDNA). The goal of the current study was to understand if approaches used previously to improve endocytosis of gene delivery vect ...
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Journal ArticleCellular and molecular bioengineering · December 2016
Electrotransfection has been widely used as a versatile, non-viral method for gene delivery. However, electrotransfection efficiency (eTE) is still low and unstable, compared to viral methods. To understand potential mechanisms of the unstable eTE, we inve ...
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Journal ArticleEur J Pharmacol · September 15, 2016
Visual impairment due to glaucoma currently impacts 70 million people worldwide. While disease progression can be slowed or stopped with effective lowering of intraocular pressure, current medical treatments are often inadequate. Fortunately, three new cla ...
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Journal ArticleBiomaterials · August 2016
Cell volume growth occurs in all living tissues. The growth exerts mechanical stresses on surrounding tissues that may alter tissue microenvironment, and have significant implications in health and diseases. However, the level of growth stress generated by ...
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Journal ArticleJ Glaucoma · April 2016
PURPOSE: To mathematically model the conventional aqueous humor outflow system with trabecular meshwork (TM) bypass and Schlemm canal (SC) dilation. METHODS: The SC was modeled as a rectangular channel with the TM modeled as a permeable membrane. The colle ...
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Journal ArticleSoft matter · April 2015
Stiffness of trabecular meshwork (TM) may play an important role in regulating outflow resistance in healthy and glaucomatous eyes. However, the current techniques for stiffness measurement can only be applied to TM dissected from human donor or large anim ...
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Journal ArticlePLoS computational biology · April 2015
Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake entails successive, increasingly strong associations between receptors on the surface of bacteria a ...
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Journal ArticleCellular and molecular bioengineering · March 2015
Endothelial cell (EC) aging and senescence are key events in atherogenesis and cardiovascular disease development. Age-associated changes in the local mechanical environment of blood vessels have also been linked to atherosclerosis. However, the extent to ...
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Journal ArticleOptics and Lasers in Engineering · February 1, 2015
Digital image correlation (DIC) is nowadays widely applied to many engineering areas as an effective optical displacement measurement technique. To minimize the potential effect of spatial sampling locations on full-field displacement measurement, this pap ...
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Journal ArticleBiomaterials · December 2014
The erroneous and unpredictable behavior of percutaneous glucose sensors just days following implantation has limited their clinical utility for diabetes management. Recent research has implicated the presence of adherent inflammatory cells as the key miti ...
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Journal ArticleInvest Ophthalmol Vis Sci · February 10, 2014
PURPOSE: Our previous work indicated that a larger circumferential Young's modulus (E) of trabecular meshwork (TM) correlated with a higher outflow facility (C) in normal human donor eyes. The current study investigated the influence of glaucomatous TM sti ...
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Journal ArticlePLoS Comput Biol · February 2014
Apoptosis is a tightly controlled process in mammalian cells. It is important for embryogenesis, tissue homoeostasis, and cancer treatment. Apoptosis not only induces cell death, but also leads to the release of signals that promote rapid proliferation of ...
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Journal ArticleMol Vis · 2014
PURPOSE: The goal of the present study was to test for the first time whether glaucomatous-like disease progression in a mouse can be assessed morphologically and functionally with spectral domain optical coherence tomography (SD-OCT). METHODS: We monitore ...
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Journal ArticleMolecular therapy. Methods & clinical development · January 2014
Electrotransfection is a technique utilized for gene delivery in both preclinical and clinical studies. However, its mechanisms are not fully understood. The goal of this study was to investigate specific pathways of endocytosis involved in electrotransfec ...
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Journal ArticleOptics and Lasers in Engineering · January 1, 2014
Digital image correlation (DIC) technique has been increasingly employed to implement surface deformation measurements in many engineering fields. Practically, it has been demonstrated that the choice of subset sizes exerts a strong influence on measuremen ...
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Journal ArticleJournal of diabetes science and technology · November 2013
BackgroundTissue response to indwelling glucose sensors remains a confounding barrier to clinical application. While the effects of fully formed capsular tissue on sensor response have been studied, little has been done to understand how tissue in ...
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Journal ArticleExperimental Mechanics · March 1, 2013
A novel subpixel registration algorithm with Gaussian windows is put forward for accurate deformation measurement in digital image correlation technique. Based on speckle image quality and potential deformation states, this algorithm can automatically mini ...
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Journal ArticleNanomedicine : nanotechnology, biology, and medicine · October 2012
Interstitial transport of large molecules and nanoparticles is an important concern in nanomedicine-mediated cancer treatment. To that end, the current study was proposed to improve the transport through enlargement of extracellular space by treating tumor ...
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Journal ArticleInvestigative ophthalmology & visual science · September 2012
PurposeAn intracanalicular scaffold (Hydrus microstent) designed to reduce intraocular pressure as a glaucoma treatment was tested in human anterior segments to determine changes in outflow facility (C).MethodsHuman eyes with no history o ...
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Journal ArticleInvest Ophthalmol Vis Sci · August 9, 2012
PURPOSE: The study was designed to determine trabecular meshwork (TM) stiffness and its relationship to outflow facility (C) in perfused normal human and porcine eyes. METHODS: Human and porcine eyes were perfused at pressures of 10, 20, 30, and 40 mm Hg t ...
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Journal ArticleCurrent pharmaceutical biotechnology · June 2012
RNA interference (RNAi) is a fundamental mechanism of gene regulation and has been harnessed to produce a new class of drugs for treatment of various diseases. A key issue in these applications is how to effectively deliver RNAi therapeutics into target ce ...
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Journal ArticleBiotechnology and bioengineering · May 2012
Three-dimensional (3D) tumor models have been established in various microfluidic systems for drug delivery and resistance studies in vitro. However, one of the main drawbacks of these models is non-uniform distribution of cells, leaving regions with very ...
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Journal ArticlePLoS One · 2012
Lowering intraocular pressure (IOP) delays or prevents the loss of vision in primary open-angle glaucoma (POAG) patients with high IOP and in those with normal tension glaucoma showing progression. Abundant evidence demonstrates that inhibition of contract ...
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Journal ArticleIntegrative biology : quantitative biosciences from nano to macro · June 2011
Advances in genetic engineering of non-pathogenic Escherichia coli (E. coli) have made this organism an attractive candidate for gene delivery vehicle. However, proliferation and transport behaviors of E. coli in three-dimensional (3D) tumor environment ar ...
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Journal ArticleMol Vis · 2011
PURPOSE: Ethacrynic acid (ECA) is a potential trabecular meshwork (TM) drug that has shown promising results in preclinical studies for treatment of primary open-angle glaucoma. However, topical application of ECA is currently limited by adverse effects in ...
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Journal ArticlePloS one · January 2011
Electric field mediated gene delivery or electrotransfection is a widely used method in various studies ranging from basic cell biology research to clinical gene therapy. Yet, mechanisms of electrotransfection are still controversial. To this end, we inves ...
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Journal ArticleJournal of pharmaceutical sciences · January 2011
The use of animal models in drug discovery studies presents issues with feasibility and ethical concerns. To address these limitations, in vitro tissue models have been developed to provide a means for systematic, repetitive, and quantitative investigation ...
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Journal ArticleCancer gene therapy · January 2011
Pulsed electric fields can enhance interstitial transport of plasmid DNA (pDNA) in solid tumors. However, the extent of enhancement is still limited. To this end, the effects of cellular resistance to electric field-mediated gene delivery were investigated ...
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Journal ArticleAnalytical and bioanalytical chemistry · October 2010
Little is known mechanistically about why implanted glucose sensors lag behind blood glucose levels in both the time to peak sensor response and the magnitude of peak sensor response. A mathematical model of glucose transport from capillaries through surro ...
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Journal ArticleAnnals of biomedical engineering · March 2010
Topical application of drugs for treatment of intraocular diseases is often limited by inadequate transport and induced toxicity in corneal tissues. To improve the drug delivery, a mathematical model was developed to numerically simulate the transport proc ...
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Journal ArticleInt J Hyperthermia · 2010
PURPOSE: In previous reports, laboratory-made lysolecithin-containing thermosensitive liposome encapsulating doxorubicin (LTSL-DOX) showed potent anticancer effects in FaDu human squamous cell carcinoma. To further study the spectrum of LTSL-DOX activity, ...
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Journal ArticleInt J Hyperthermia · September 2008
Previous data have demonstrated that doxorubicin (DOX) released from a lysolecithin-containing thermosensitive liposome (LTSL) can shut down blood flow in a human tumor xenograft (FaDu) in mice when the treatment is combined with hyperthermia (HT), suggest ...
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Journal ArticleMolecular cancer therapeutics · August 2008
Pulsed electric fields have been shown to enhance interstitial transport of plasmid DNA (pDNA) in solid tumors in vivo. However, the extent of enhancement is still limited partly due to the collagen component in extracellular matrix. To this end, effects o ...
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Journal ArticleJournal of pharmaceutical sciences · February 2008
Gene therapy has a great potential in cancer treatment. However, the efficacy of cancer gene therapy is currently limited by the lack of a safe and efficient means to deliver therapeutic genes into the nucleus of tumor cells. One method under investigation ...
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Journal ArticleMicrovascular research · January 2008
Angiogenesis involves interactions among various molecules and cells. To understand the complexity of interactions, we developed a mathematical model to numerically simulate angiogenesis induced by basic fibroblast growth factor (bFGF) in the corneal pocke ...
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Journal ArticleExperimental biology and medicine (Maywood, N.J.) · January 2008
Pulsed electric field has been widely used as a nonviral gene delivery platform. The delivery efficiency can be improved through quantitative analysis of pore dynamics and intracellular transport of plasmid DNA. To this end, we investigated mechanisms of c ...
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Journal ArticleMicrovascular research · January 2008
Understanding mechanisms of formation of vascular networks under different experimental conditions is essential for improving treatment of angiogenesis-dependent diseases. To this end, we investigated the dose response of angiogenesis to basic fibroblast g ...
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Journal ArticleBioelectrochemistry (Amsterdam, Netherlands) · November 2007
Local pulsed electric field application is a method for improving non-viral gene delivery. Mechanisms of the improvement include electroporation and electrophoresis. To understand how electrophoresis affects pDNA delivery in vivo, we quantified the magnitu ...
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Journal ArticleAnnals of biomedical engineering · July 2007
One of the key issues in electric field-mediated molecular delivery into cells is how the intracellular field is altered by electroporation. Therefore, we simulated the electric field in both the extracellular and intracellular domains of spherical cells d ...
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Journal ArticleMol Vis · February 22, 2007
PURPOSE: One of the current limitations in developing novel glaucoma drugs that target the trabecular meshwork (TM) is the induced corneal toxicity from eyedrop formulations. To avoid the corneal toxicity, an alternative approach would be to deliver TM dru ...
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Journal ArticleAnalytical chemistry · January 2007
In vitro microdialysis glucose sampling was used to test the transient and steady-state suitability of antifouling hydrogel coatings, composed of 2-hydroxyethyl methacrylate, vinylpyrrolidinone, and poly(ethylene glycol). The in vitro glucose diffusion coe ...
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Journal ArticleBioelectrochemistry (Amsterdam, Netherlands) · October 2006
The interstitial space is a rate limiting physiological barrier to non-viral gene delivery. External pulsed electric fields have been proposed to increase DNA transport in the interstitium, thereby improving non-viral gene delivery. In order to characteriz ...
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Journal ArticleAnnals of biomedical engineering · October 2006
The intratumoral field, which determines the efficiency of electric field-mediated drug and gene delivery, can differ significantly from the applied field. Therefore, we investigated the distribution of the electric field in mouse tumors and tissue phantom ...
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Journal ArticleCancer Chemother Pharmacol · August 2006
To quantitatively evaluate the extravasation, accumulation and selectivity to tumor tissues of liposomal vincristine (LV), dorsal skin-fold window chambers on athymic mice with or without LX-1, a human small cell lung cancer, xenograft implants and fluores ...
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Journal ArticleAnnals of biomedical engineering · July 2006
Efficiency of intratumoral infusion for drug and gene delivery depends on intrinsic tissue structures as well as infusion-induced changes in these structures. To this end, we investigated effects of infusion pressure (P(inf)) and infusion-induced tissue de ...
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Journal ArticleInt J Hyperthermia · May 2006
Drug delivery systems have been developed for cancer therapy in an attempt to increase the tumour drug concentration while limiting systemic exposure. Liposomes have achieved passive targeting of solid tumours through enhanced vascular permeability, which ...
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Journal ArticleJ Natl Cancer Inst · March 1, 2006
BACKGROUND: Delivery of anticancer therapeutic agents to solid tumors is problematic. Macromolecular drug carriers are an attractive alternative drug delivery method because they appear to target tumors and have limited toxicity in normal tissues. We inves ...
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Journal ArticleMol Cancer Ther · February 2006
Recent studies have shown that up to 90% of viral vectors could disseminate to normal organs following intratumoral infusion. The amount of dissemination might be dependent on the infusion conditions. Therefore, we investigated the effects of infusion rate ...
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Journal ArticleAnnals of biomedical engineering · January 2006
It is a challenge to deliver therapeutic genes to tumor cells using viral vectors because (i) the size of these vectors are close to or larger than the space between fibers in extracellular matrix and (ii) viral proteins are potentially toxic in normal tis ...
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Journal ArticleAngiogenesis · 2006
GW5638 is a novel tissue-selective estrogen receptor (ER) modulator. Structurally, it is a derivative of tamoxifen that is known for its inhibitory effects on angiogenesis in an ER-independent manner. Therefore, it is possible that GW5638 has the same effe ...
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Journal ArticleProceedings of the 2005 Summer Bioengineering Conference · December 1, 2005
Electric field-mediated gene delivery is a promising therapeutic modality that uses an externally applied voltage source to introduce exogenous genetic materials to target cells by field-dependent phenomena, such as electrophoresis and electroporation. In ...
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Journal ArticleProceedings of the 2005 Summer Bioengineering Conference · December 1, 2005
Potential trabecular meshwork (TM) drugs can be delivered with a lower concentration on the cornea surface over a long period of time for reducing the induced corneal toxicity. To determine the concentration of drugs that can be achieved in the TM, we deve ...
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Journal ArticleCancer Res · September 1, 2005
Intratumoral infusion is the most commonly used method for viral gene delivery in clinical trials for cancer treatment. However, a potential problem in this approach is that viral vectors may disseminate from tumor to normal tissues during and after the in ...
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Journal ArticleBr J Cancer · April 25, 2005
Systemic virus dissemination is a potential problem during local gene delivery in solid tumours. However, the kinetics and pathways of the dissemination have not been well characterised during the first 24 h after the infusion is started. To this end, we i ...
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Journal ArticleMol Cancer Ther · October 2004
Liposomal drugs accumulate only in perivascular regions in tumors after i.v. injection. Thus, they cannot kill tumor cells in deeper tissue layers. To circumvent this problem, we investigated effects of doxorubicin (DOX) encapsulated in a lysolecithin-cont ...
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Journal ArticleIEEE transactions on nanobioscience · September 2004
Externally applied electric fields play an important role in many therapeutic modalities, but the fields they produce inside cells remain largely unknown. This study makes use of a three-dimensional model to determine the electric field that exists in the ...
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Journal ArticleBiomaterials · August 2004
Ethacrynic acid (ECA) is a potential glaucoma drug that can reduce intraocular pressure. However, conventional methods of ECA administration may cause toxicity to normal eye tissues and are inconvenient to patients. Therefore, we developed and characterize ...
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Journal ArticleBioelectrochemistry (Amsterdam, Netherlands) · April 2004
Interstitial transport of DNA is a rate-limiting step in electric field-mediated gene delivery in vivo. Interstitial transport of macromolecules, such as plasmid DNA, over a distance of several cell layers, is inefficient due to small diffusion coefficient ...
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Journal ArticleConf Proc IEEE Eng Med Biol Soc · 2004
Intratumoral infusion, a routine method for local gene delivery in solid tumors, may cause a systemic dissemination of gene vectors. This is because tumor vessels are intrinsically leaky and intratumoral injection can also result in damage of tumor vessels ...
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Journal ArticleMol Cancer Ther · November 2003
Intratumoral injection is a routine method for local viral gene delivery that may improve interstitial transport of viral vectors in tumor tissues and reduce systemic toxicity. However, the concentration of transgene products in normal organs, such as in t ...
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Journal ArticleJ Neurooncol · October 2003
TP-38 is a recombinant chimeric targeted toxin composed of the EGFR binding ligand TGF-alpha and a genetically engineered form of the Pseudomonas exotoxin, PE-38. After in vitro and in vivo animal studies that showed specific activity and defined the maxim ...
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Journal ArticleClin Cancer Res · February 2003
PURPOSE: The purpose of this study was to evaluate the feasibility of incorporating a novel wound angiogenesis assay into a Phase I study of BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor, and to determine whether the wound angiogenesis as ...
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Journal ArticleInt J Hyperthermia · 2003
Drug delivery to solid tumors may be enhanced through increasing the available volume fraction (K(AV)) of drugs. Therefore, two approaches were investigated that may increase K(AV) of dextrans in a rat fibrosarcoma: (a) damaging cells in tumours via ex viv ...
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Journal ArticleWound Repair Regen · 2003
Full-thickness dermal biopsies were performed in healthy volunteers to establish the range of angiogenic responses in wound healing in a normal population. Four-millimeter punch biopsies were made in the forearms of 15 healthy volunteers. Each wound was ev ...
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Journal ArticleAnnual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings · December 1, 2002
To reduce dissemination of viral vectors and their gene products during and after local gene therapy, we mixed adenoviral vectors with an alginate solution and subsequently injected the mixture into mouse tumors. We found that the alginate solution signifi ...
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Journal ArticleAnnual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings · December 1, 2002
Interstitial penetration is critical for drug delivery in tumor tissues. To experimentally determine the penetration depth of macromolecules at the steady state, rat fibrosarcoma tissues were sectioned into 600μm slices and incubated in solutions of dextra ...
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Journal ArticleAnnual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings · December 1, 2002
Transscleral drug delivery is an effective method for treatment of eye diseases in posterior segment. Therefore, we investigated transscleral permeability of ethacrynic acid (ECA), a potential drug for treating glaucoma. To determine the ex vivo permeabili ...
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Journal ArticleAnnual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings · December 1, 2002
Interstitial transport of DNA is a rate-limiting step in electric field-mediated gene delivery. Interstitial transport of macromolecules such as plasmid DNA is limited by small diffusion coefficient, large diffusion distance and inadequate convection. Here ...
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Journal ArticleGene Ther · October 2002
Interstitial transport is a crucial step in plasmid DNA-based gene therapy. However, interstitial diffusion of large nucleic acids is prohibitively slow. Therefore, we proposed to facilitate interstitial transport of DNA via pulsed electric fields. To test ...
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Journal ArticleJournal of pharmaceutical and biomedical analysis · April 2002
One of the critical issues in microdialysis sampling is how to predict the extraction fraction (E(d)), based on transport properties of analytes in both tissues and probes. A one-dimensional (1-D) model has been used widely in previous studies to predict E ...
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Journal ArticleDis Markers · 2002
The purpose of this report is to present an overview of the use of fluorescence imaging in vivo, with particular emphasis on oncology. It is important to note, however, that many of the methods described herein have been applied to the study of non-maligna ...
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Journal ArticleAnnals of biomedical engineering · December 2001
Molecular exclusion in tumor tissues is one of the limiting factors for drug delivery to tumor cells. It can be quantified by the available volume fraction of solutes (K(AV)). We found in a previous study that K(AV) of dextran in tumor tissues decreased sh ...
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Journal ArticleAmerican journal of physiology. Heart and circulatory physiology · August 2001
Intratumoral infusion has a potential for improving distribution of drugs. To optimize the infusion, we developed a novel technique to quantify the distribution volume of color molecules (Vd) in solid tumors. Evans blue-labeled albumin was infused locally ...
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Journal ArticleCancer Res · April 15, 2001
Plasmids may have unique advantages as a gene delivery system. However, a major obstacle is the low in vivo transduction efficiency. In this study, an electroporation-based gene transduction approach was taken to study the effect of interleukin (IL)-2 or I ...
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Journal ArticleMicrovascular research · January 2001
Angiogenesis plays important roles in many physiologic and pathologic processes in the body. To understand mechanisms of angiogenesis, we developed a mathematical model for quantitative analysis of various biological events involved in angiogenesis. Our mo ...
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Journal ArticleAm J Physiol Heart Circ Physiol · December 2000
Convective transport of therapeutic agents in solid tumors can be improved through intratumoral infusion. To optimize the convection, we investigated the dependence of the hydraulic conductivity on tissue deformation induced by interstitial fluid pressure ...
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Journal ArticleAnnals of Biomedical Engineering · December 1, 2000
The mobility of plasmid DNA in high amplitude/low duration electric fields was assessed. The influences of pulse amplitude, pulse duration and agarose gel concentration on mobility were compared. Movement of plasmid DNA in an electroporation setting was in ...
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Journal ArticleAmerican Society of Mechanical Engineers, Bioengineering Division (Publication) BED · December 1, 2000
We investigated DNA transport in the interstitial space and across cell membrane facilitated by intratumoral infusion and in vivo electroporation, respectively. In the study, a rat fibrosarcoma was perfused ex vivo, and apparent hydraulic conductivity (Kap ...
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Journal ArticleAnnals of Biomedical Engineering · December 1, 2000
To optimize intramural infusion of macromolecules, a novel technique was developed to quantify the distribution volume of color molecules in solid tumors. It was shown that infusion pressure and volume significantly affects the distribution volume of drugs ...
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Journal ArticleAnnals of Biomedical Engineering · December 1, 2000
An ex vivo method was developed to quantify available volume fraction (Kav) in tumor tissues and polymer gels. It was shown that Kav is an important transport parameter that depends on physichochemical properties of drugs and tissue structures. ...
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Journal ArticleAnnals of Biomedical Engineering · December 1, 2000
To understand the mechanisms of angiogenesis, a mathematical model was developed for quantitative analysis of various biological events involved in angiogenesis. The model was focused on twodimensional angiogenesis in the cornea. The model considered diffu ...
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Journal ArticleBritish journal of cancer · May 2000
Molecular charge is one of the main determinants of transvascular transport. There are, however, no data available on the effect of molecular charge on microvascular permeability of macromolecules in solid tumours. To this end, we measured tumour microvasc ...
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ConferenceASME International Mechanical Engineering Congress and Exposition, Proceedings (IMECE) · January 1, 2000
We investigated DNA transport in the interstitial spaceand across cell membrane facilitated by intratumoral infusionand in vivo electroporation, respectively. In the study, a ratfibrosarcoma was perfused ex vivo, and apparent hydraulicconductivity (Kaap) w ...
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Journal ArticleAnnals of Biomedical Engineering · 2000
To understand the mechanisms of angiogenesis, a mathematical model was developed for quantitative analysis of various biological events involved in angiogenesis. The model was focused on twodimensional angiogenesis in the cornea. The model considered diffu ...
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Journal ArticleAnnals of Biomedical Engineering · 2000
The mobility of plasmid DNA in high amplitude/low duration electric fields was assessed. The influences of pulse amplitude, pulse duration and agarose gel concentration on mobility were compared. Movement of plasmid DNA in an electroporation setting was in ...
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Journal ArticleAnnals of Biomedical Engineering · 2000
To optimize intramural infusion of macromolecules, a novel technique was developed to quantify the distribution volume of color molecules in solid tumors. It was shown that infusion pressure and volume significantly affects the distribution volume of drugs ...
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ConferenceAnnual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings · December 1, 1999
Intratumor infusion has been used to deliver therapeutic agents to tumor cells. The distribution volume of infused agents depends on the hydraulic conductivity (K) in tumors, which may vary with the infusion pressure. Therefore, we quantified K in a rat fi ...
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Journal ArticleCancer Res · August 15, 1999
Steric exclusion of molecules in the extravascular space of tissues can be quantified by the available volume fraction (K(AV)). Despite its clinical importance, however, there is a paucity of data in the literature regarding the available volume fraction o ...
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Journal ArticleCancer research · August 1999
The goal of this investigation was to measure changes in vascular permeability, pore cutoff size, and number of transvascular transport pathways as a function of time and in response to vascular endothelial growth factor (VEGF), placenta growth factor (PIG ...
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Journal ArticleProceedings of the National Academy of Sciences of the United States of America · September 1998
The sequence of events that leads to tumor vessel regression and the functional characteristics of these vessels during hormone-ablation therapy are not known. This is because of the lack of an appropriate animal model and monitoring technology. By using i ...
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Journal ArticleSeminars in radiation oncology · July 1998
The microvessel wall is a barrier for the delivery of various therapeutic agents to tumor cells. Tumor microvessels are, in general, more permeable to macromolecules than normal vessels. The hyperpermeability is presumably due to the existence of large por ...
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Journal ArticleProceedings of the National Academy of Sciences of the United States of America · April 1998
Novel anti-neoplastic agents such as gene targeting vectors and encapsulated carriers are quite large (approximately 100-300 nm in diameter). An understanding of the functional size and physiological regulation of transvascular pathways is necessary to opt ...
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Journal ArticleJ Surg Oncol · September 1997
BACKGROUND AND OBJECTIVES: The median of pO2 values in tumor measured by Eppendorf "Histograph" with a needle-type electrode has been used as a prognostic indicator in cancer patients. However, it is not established that a pretreatment measured pO2 value c ...
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Journal ArticleThe American journal of pathology · September 1997
It is generally accepted that the host microenvironment influences tumor biology. There are discrepancies in growth rate, metastatic potential, and efficacy of systemic treatment between ectopic and orthotopic tumors. Liver is the most common and critical ...
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Journal ArticleProceedings of the National Academy of Sciences of the United States of America · March 1997
Binding is crucial to the function of most biologically active molecules, but difficult to quantify directly in living tissue. To this end, fluorescence recovery after photobleaching was used to detect the immobilization of fluorescently labeled ligand cau ...
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Journal ArticleThe American journal of pathology · February 1997
The present study was designed to define the role of nitric oxide (NO) in tumor microcirculation, through the direct intravital microcirculatory observations after administration of NO synthase (NOS) inhibitor and NO donor both regionally and systemically. ...
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Journal ArticleNature medicine · February 1997
The partial pressure of oxygen (pO2) and pH play critical roles in tumor biology and therapy. We report here the first combined, high-resolution (< or = 10 microns) measurements of interstitial pH and pO2 profiles between adjacent vessels in a human tumor ...
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Journal ArticleInternational journal of microcirculation, clinical and experimental · January 1997
Basic fibroblast growth factor (bFGF), a constituent of bone and cartilage matrix, has been shown to be a potent mitogen for osteoblasts and chondrocytes and yet an inhibitor of chondrocyte terminal differentiation in cell culture. To characterize the effe ...
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Journal ArticleProceedings of the National Academy of Sciences of the United States of America · December 1996
The hyperpermeability of tumor vessels to macromolecules, compared with normal vessels, is presumably due to vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) released by neoplastic and/or host cells. In addition, VEGF/VPF is a pot ...
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Journal ArticleMicrocirculation (New York, N.Y. : 1994) · December 1996
ObjectiveTo develop a new method for determining the relative importance of convection versus diffusion in macromolecular transport across tumor microvessel walls.MethodsThe human colon adenocarcinoma LS174T was transplanted in the dorsal ...
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Journal ArticleBritish journal of cancer · October 1996
Tumour pH plays a significant role in cancer treatment. However, because of the limitations of the current measurement techniques, spatially and temporally resolved pH data, obtained non-invasively in solid tumours, are not available. Fluorescence ratio im ...
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Journal ArticleActa orthopaedica Scandinavica · August 1996
We have characterized the effect of bone graft treatment by heating or freezing (with or without dimethyl sulfoxide (DMSO)). Tissue culture and dorsal skin-fold chambers in mice were used as sites to quantify the effect on angiogenesis, growth and calcific ...
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Journal ArticleThe American journal of pathology · July 1996
A prerequisite for the development of novel angiogenic and anti-angiogenic agents is the availability of routine in vivo assays that permit 1) repeated, long-term quantitation of angiogenesis and 2) physiological characterization of angiogenic vessels. We ...
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Journal ArticleBlood · November 1995
P-selectin-mediated rolling is believed to be important in the recruitment of leukocytes to tissue after ischemia-reperfusion injury. The dorsal skin chamber was used to examine differences in the rolling and stable adhesion of circulating leukocytes in su ...
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Journal ArticleCancer research · September 1995
Molecular size is one of the key determinants of transvascular transport of therapeutic agents in tumors. However, there are no data in the literature on the molecular size dependence of microvascular permeability in tumors. Therefore, we measured microvas ...
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Journal ArticleResearch in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie · January 1995
Nonsteroidal anti-inflammatory agents have been used experimentally and clinically to suppress a variety of physiological events, including angiogenesis and formation of bone. The exact mechanisms by which indomethacin alters skeletal tissue generation are ...
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Journal ArticleThe American journal of physiology · October 1994
The present study had two goals: 1) to establish an animal model in which a large network of the initial lymphatics of the skin can be investigated in vivo and 2) to measure effective flow velocity (defined as axial component of the flow velocity) in the l ...
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Journal ArticleCancer research · September 1994
Many brain tumors are highly resistant to chemotherapy, presumably due to the presence of a tight blood-tumor barrier. For a better understanding of the regulation of this barrier by the brain environment, a new intravital microscopy model was established ...
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Journal ArticleLaboratory investigation; a journal of technical methods and pathology · August 1994
BackgroundUnderstanding the regulation of vascularization and formation of bone after skeletal trauma is essential for the development of methods to promote healing. The lack of information on the biology of bone healing led us to establish an exp ...
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Journal ArticleCancer research · July 1994
Microvascular permeability and interstitial penetration of sterically stabilized liposomes in both normal s.c. tissue and human colon adenocarcinoma LS174T xenograft were quantified by using the dorsal skin-fold chamber implanted in severe combined immunod ...
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Journal ArticleProceedings of the National Academy of Sciences of the United States of America · March 1994
Simultaneous measurements of intravascular and interstitial oxygen partial pressure (PO2) in any tissue have not previously been reported, despite the importance of oxygen in health and in disease. This is due to the limitations of current techniques, both ...
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Journal ArticleBiophysical journal · December 1993
A new method for the measurement of diffusion in thick samples is introduced, based upon the spatial Fourier analysis of Tsay and Jacobson (Biophys. J. 60: 360-368, 1991) for the video image analysis of fluorescence recovery after photobleaching (FRAP). In ...
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Journal ArticleMicrovascular research · May 1993
A novel method was developed to measure the effective permeability of microvessels in three-dimensional tumors. Two unique features characterized our approach: (i) Texas Red (with peak excitation and peak emission wavelengths of 596 and 615 nm, respectivel ...
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ConferenceAmerican Society of Mechanical Engineers, Heat Transfer Division, (Publication) HTD · December 1, 1992
We have characterized steps in drug delivery using two tumor models: (i) an `isolated' tumor which grows in the body with only one arterial input and one venous output, so that we can measure directly what is going into a tumor and what is leaving a tumor; ...
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Journal ArticleCancer research · December 1992
To date, most quantitative information on tumor angiogenesis, microcirculation, and transport has been derived from rodent tumors grown in transparent chamber preparations. In this paper we present a chamber technique adapted to immunodeficient mice for th ...
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Journal ArticleCancer research · October 1992
A mathematical model is developed to describe the concentration profiles around individual tumor blood vessels for two-step approaches to cancer treatment. The model incorporates plasma pharmacokinetics, interstitial diffusion, reversible binding between a ...
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Journal ArticleJournal of biomechanical engineering · August 1991
In this paper a new theoretical framework is presented for analyzing the filtration and macromolecular convective-diffusive transport processes in the intimal region of an artery wall with widely dispersed macromolecular cellular leakage sites, as proposed ...
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Journal ArticleCancer research · June 1991
Bifunctional antibodies (BFA) and enzyme-conjugated antibodies (ECA) can be used to preferentially deliver a hapten or drug to tumor sites for diagnosis and therapy. We present here a simple pharmacokinetic model for the above two systems by considering on ...
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Journal ArticleJournal of biomechanical engineering · February 1991
A prototype mathematical model for Brown and Goldstein's pioneering studies on the LDL receptor mediated pathway for the regulation of the cellular content of cholesterol has been developed in this paper. In order to analyze the essential features of this ...
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Journal ArticleAmerican Society of Mechanical Engineers, Bioengineering Division (Publication) BED · December 1, 1990
Macromolecular transport across the arterial wall is closely linked to a variety of processes in the intima that are believed to play an important role in the subendothelial accumulation of lipid and the formation of the early foam cell lesion. In this pap ...
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